WO2020138551A1 - Filter having heavy metal and formaldehyde removal capability - Google Patents

Filter having heavy metal and formaldehyde removal capability Download PDF

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Publication number
WO2020138551A1
WO2020138551A1 PCT/KR2018/016802 KR2018016802W WO2020138551A1 WO 2020138551 A1 WO2020138551 A1 WO 2020138551A1 KR 2018016802 W KR2018016802 W KR 2018016802W WO 2020138551 A1 WO2020138551 A1 WO 2020138551A1
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WO
WIPO (PCT)
Prior art keywords
formula
filter
heavy metal
cyclam
trientine
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PCT/KR2018/016802
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French (fr)
Korean (ko)
Inventor
구영삼
손기남
Original Assignee
(주)에프엔지리서치
구영삼
손기남
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Priority to PCT/KR2018/016802 priority Critical patent/WO2020138551A1/en
Publication of WO2020138551A1 publication Critical patent/WO2020138551A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24D—CIGARS; CIGARETTES; TOBACCO SMOKE FILTERS; MOUTHPIECES FOR CIGARS OR CIGARETTES; MANUFACTURE OF TOBACCO SMOKE FILTERS OR MOUTHPIECES
    • A24D3/00—Tobacco smoke filters, e.g. filter-tips, filtering inserts; Filters specially adapted for simulated smoking devices; Mouthpieces for cigars or cigarettes
    • A24D3/06—Use of materials for tobacco smoke filters
    • A24D3/08—Use of materials for tobacco smoke filters of organic materials as carrier or major constituent
    • A—HUMAN NECESSITIES
    • A41—WEARING APPAREL
    • A41D—OUTERWEAR; PROTECTIVE GARMENTS; ACCESSORIES
    • A41D13/00—Professional, industrial or sporting protective garments, e.g. surgeons' gowns or garments protecting against blows or punches
    • A41D13/05—Professional, industrial or sporting protective garments, e.g. surgeons' gowns or garments protecting against blows or punches protecting only a particular body part
    • A41D13/11—Protective face masks, e.g. for surgical use, or for use in foul atmospheres
    • A—HUMAN NECESSITIES
    • A62—LIFE-SAVING; FIRE-FIGHTING
    • A62B—DEVICES, APPARATUS OR METHODS FOR LIFE-SAVING
    • A62B18/00—Breathing masks or helmets, e.g. affording protection against chemical agents or for use at high altitudes or incorporating a pump or compressor for reducing the inhalation effort
    • A62B18/02—Masks
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D39/00—Filtering material for liquid or gaseous fluids
    • B01D39/14—Other self-supporting filtering material ; Other filtering material
    • B01D39/16—Other self-supporting filtering material ; Other filtering material of organic material, e.g. synthetic fibres
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D46/00—Filters or filtering processes specially modified for separating dispersed particles from gases or vapours
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F24—HEATING; RANGES; VENTILATING
    • F24F—AIR-CONDITIONING; AIR-HUMIDIFICATION; VENTILATION; USE OF AIR CURRENTS FOR SCREENING
    • F24F13/00—Details common to, or for air-conditioning, air-humidification, ventilation or use of air currents for screening
    • F24F13/28—Arrangement or mounting of filters

Definitions

  • the present invention relates to a filter for effectively removing heavy metals and formaldehyde, and more particularly, to an air filter, a cigarette filter, and an air mask that can be used in various air conditioning systems such as household and automobile air purifiers and air conditioners.
  • Fine dust is dust with an average particle diameter of 10 ⁇ m or less
  • ultrafine dust is dust with an average particle size of 2.5 ⁇ m or less, causing various respiratory diseases such as asthma and lung function, and various skin diseases such as dermatitis, allergies and atopy. It is known as a factor.
  • Fine dust varies depending on the region, environment, and season, but Hg (mercury), Pb (lead), Cd (cadmium), As (arsenic), Cr (chrome), Cu (copper), Ni (nickel), and Zn ( Zinc), Mn (manganese), Co (cobalt), Sn (tin), etc., contains about 20% of harmful heavy metals, and is reported to cause various diseases.
  • filters of various materials and standards are developed and sold according to the system. These filters are classified into filtration type, electrostatic type, collision adhesion type, adsorption type filter, and dust type, medium size, fine size, and gas removal type filters according to the dust collection method. Composite filters produced by overlapping are used.
  • Filter materials include paper filters, nonwoven filters, vinyl chloride filters, HEPA filters and carbon, activated carbon, zeolite, silica gel, alumina, ferric oxide, and other adsorbents.
  • the HEPA filter can remove fine dust of 0.3 ⁇ m or less depending on the grade, but the cost is high and the adsorption performance of heavy metals and formaldehyde is still limited.
  • harmful heavy metals such as As (arsenic), Kaduchen (Cd), and Ni (nickel) are included in the tobacco (cigarette) component in addition to fine dust, and when they smoke, they enter the respiratory tract with nicotine, tyr, and harmful gases, causing lung cancer and It is known to cause the same disease.
  • Common cigarettes are cigarette filters made of acetate tow fibers to filter tar, nicotine, and carbon monoxide during smoking, and there are added porous adsorbents such as activated carbon or zeolite to increase filter performance.
  • porous adsorbents such as activated carbon or zeolite have a certain effect on the removal of nicotine or tar, but have no great effect on adsorption and removal of heavy metals and formaldehyde.
  • the present invention is to solve the above problems, provides an air filter material that can effectively remove heavy metals and formaldehyde, and can be used in various air conditioning devices such as air cleaners, air conditioners, and air circulation systems using these filters.
  • the purpose is to provide an air filter, a cigarette filter, and an air mask.
  • the present invention is a trientine or a trientine derivative represented by the following Chemical Formula 1, a cyclene or cyclene derivative represented by the following Chemical Formula 2 as an active ingredient for removing heavy metals and formaldehyde, the following Chemical Formula It provides a filter having a heavy metal and formaldehyde removal ability, including at least one selected from a cyclam or a cyclam derivative represented by 3.
  • R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen, -R 7 -COOH or a salt thereof, R 7 is C 1 ⁇ C 5 aliphatic, A substituted or unsubstituted aromatic ring, or a heterocyclic 6-membered or 5-membered ring.
  • the active ingredient is preferably selected from trientine of the following formula 1a, cyclene of the formula 2a, cyclam of the formula 3a or salts thereof.
  • the trientine derivative is preferably selected from compounds represented by the following formulas 1b to 1d or salts thereof.
  • R 8 and R 9 are each independently hydrogen or an alkyl group of C 1 to C 4 , and X is oxygen (O), sulfur (S) or nitrogen (N).)
  • the cyclone derivative is preferably selected from compounds represented by the following formulas 2b to 2d or salts thereof.
  • R 8 and R 9 are each independently hydrogen or an alkyl group of C 1 to C 4 , and X is oxygen (O), sulfur (S) or nitrogen (N).)
  • the cyclam derivative is preferably selected from compounds represented by the following formulas 3b to 3d or salts thereof.
  • R 8 and R 9 are each independently hydrogen or an alkyl group of C 1 to C 4 , and X is oxygen (O), sulfur (S) or nitrogen (N).)
  • the filter containing the active ingredient according to the present invention is excellent in removing heavy metals present in fine dust, and air filters, cigarette filters, and air that can be used in various air conditioning devices such as air cleaners, air conditioners, and air circulation systems It can be usefully used as a mask material.
  • the "filter” includes an air filter that can be used in various air conditioning apparatuses such as an air purifier, an air conditioner, and an air circulation system, as well as a cigarette filter and a filter for an air mask.
  • the present inventors have conducted various studies on heavy metal chelating agents to develop filter materials that can effectively remove heavy metals and formaldehyde, which is a primary carcinogen, and are currently used as pharmaceuticals, trientine, cyclene, and cyclam. When these and their derivatives are used as heavy metal and formaldehyde adsorbents of filters, it has been confirmed that the removal ability is remarkably excellent, leading to the present invention.
  • Trientine (trientine) is represented by the following formula 1a, it is called Triethylenetetramine (TETA).
  • Cyclen is a general name of 1,4,7,10-tetraazacyclododecane represented by the following Chemical Formula 2a, and is used in nuclear medicine contrast agents by forming chelates through coordination with gadolinium (Gd).
  • Cyclam is a general name of 1,4,8,11-tetraazacyclotetradecane represented by the following Chemical Formula 3a and is used in nuclear medicine contrast media.
  • Chelating agents such as trientine, cyclene, and cyclam are well known for medicinal use of copper as a contrast material or to release copper from the body through oral or vascular administration methods, but no research on its use as a filter material has been reported.
  • trientine, cyclene, and cyclam compounds are useful as filter components for removing heavy metals.
  • results for removal of heavy metals in fine dust, skin irritation, and toxicity are disclosed.
  • Trientine, cyclene, and cyclam compounds are known to be harmful to conventional skin, but the experimental results of the present invention show no skin irritation or toxicity in the use of an amount effective to remove heavy metals on the skin, or very low as acceptable as a filter material. was confirmed.
  • the present invention is effective for at least one selected from trientine or trientine derivatives represented by the following Chemical Formula 1, cyclene or cyclene derivatives represented by the following Chemical Formula 2, cyclam or cyclam derivatives represented by the following Chemical Formula 3
  • a filter having a heavy metal and formaldehyde removal ability as a component.
  • R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen, -R 7 -COOH or a salt thereof, R 7 is C 1 ⁇ C 5 aliphatic, A substituted or unsubstituted aromatic ring, or a heterocyclic 6-membered or 5-membered ring.
  • the air filter of the present invention is characterized in that it contains trientine, cyclene, cyclam or salts thereof as an active ingredient for removing heavy metals and formaldehyde.
  • trientine derivative, the cyclene derivative, and the cyclam derivative according to the present invention are selected from compounds represented by the following formulas 1b to 3d.
  • R 8 and R 9 are each independently hydrogen or an alkyl group of C 1 to C 4 , and X is oxygen (O), sulfur (S) or nitrogen (N).)
  • the content of the trientine or trientine derivative, cyclene or cyclene derivative, cyclam or cyclam derivative compound of the present invention can be changed depending on the use and material of the filter.
  • the active ingredient of the present invention is not limited to the weight of the filter containing the active ingredient, but may be contained in 0.001 to 5.0% by weight, preferably 0.1 to 3.0% by weight, more preferably 0.2 to 2.0% by weight.
  • the trientine or trientine derivatives of the present invention, cyclene or cyclic derivatives, cyclam or cyclam derivative compounds may be used in the form of water-soluble salts.
  • the compounds of the present invention include the form of hydrochloride, sodium salt, potassium salt. More preferably, the compound of the present invention is in the form of dihydrochloride or tetrachloride. Preparation of the salt can be performed by a known method.
  • the filter of the present invention may be prepared by preparing the active ingredient in the form of an aqueous solution or a solution, impregnating the filter material used conventionally, or spraying it and drying it.
  • the filter material of the present invention is commonly used as a filter material to which various adsorbents such as paper filter, nonwoven filter, fiber filter, vinyl chloride filter, HEPA filter, carbon, activated carbon, zeolite, silica gel, alumina, ferric oxide, etc. are added. It may be a filter material.
  • the filter of the present invention may be used as a single filter, or may be used as a composite filter overlapping other filter materials.
  • Example 2 4 ,4',4'',4''-( ((ethane-1,2-diylbis( Preparation of (4-carboxyphenyl)azanediyl))bis(ethane-2,1-diyl))bis(azanetriyl))tetrabenzoic acid (Formula 1f)
  • Triethylenetetramine 10.0g, ethyl 4-bromobenzoate 108,1g, t-BuONa 46.0g and toluene 600ml were added and stirred. After heating up to 35°C, 2.8g of 50% (t-Bu) 3 P toluene solution was added, stirred for 30 minutes, heated to 50°C, and then 2.0g of Pd(dba)2 was added and heated to reflux stirring to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer.
  • Triethylenetetramine 10.0g, ethyl 5-bromonicotinate 108,5g, t-BuONa 46.0g and Xylene 600ml are added and stirred. After heating up to 35°C, 2.8g of 50% (t-Bu) 3 P toluene solution was added, stirred for 30 minutes, heated to 50°C, and then 2.0g of Pd(dba)2 was added and heated to reflux stirring to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer.
  • Triethylenetetramine 10.0g, ethyl 5-bromofuran-2-carboxylate 103,3g, t-BuONa 46.0g and toluene 600ml were added and stirred. After heating up to 35°C, 2.8g of 50% (t-Bu) 3 P toluene solution was added, stirred for 30 minutes, heated to 50°C, and then 2.0g of Pd(dba)2 was added and heated to reflux stirring to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer.
  • Example 8 5 Preparation of ,5',5'',5'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrakis(furan-2-carboxylic acid) (Formula 2h)
  • Example 10 4 ,4',4'',4''-(1,4,8,11- tetraazacyclotetradecane Preparation of -1,4,8,11-tetrayl)tetrabenzoic acid (Formula 3f)
  • Cyclam 10.0g, ethyl 5-bromonicotinate 50.3g, t-BuONa 24.0g and xylene 400ml were added and stirred. After heating up to 35°C, add 2.0g of 50% (t-Bu) 3 P toluene solution, stir for 30 minutes, heat up to 50°C, add 1.5g of Pd(dba)2, heat up, and stir to reflux to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer.
  • Example 12 5 Preparation of ,5',5'',5'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetrakis (furan-2-carboxylic acid) (Formula 3h)
  • Trientine, cyclene, cyclam, and the trientine derivatives, cyclene derivatives, and cyclam derivatives prepared in Examples 1 to 12 were prepared as a 1% aqueous solution, and then commercially available 5T nonwoven fabric for air filters ( PET material) was purchased, cut into 10 cm * 10 cm, sprayed with the aqueous solution for 30 seconds, sufficiently wetted, and then dried for 3 hours to prepare a filter containing the active ingredient according to the present invention.
  • Each active component of the air filter is shown in Table 1 below.
  • Example 13 Trientine Example 14
  • Example 1 Example 15
  • Example 2 Example 3
  • Example 4 Example 18 Cyclen
  • Example 19 Example 5
  • Example 20 Example 6
  • Example 7 Example 22
  • Example 8 Example 23 Cyclam Example 24
  • Example 9 Example 25
  • Example 10 Example 26
  • Example 11 Example 27
  • Example 12 Comparative Example 1 -
  • the manufactured filters are placed side by side in a closed space, and a large amount of fine dust collected from the outside is put in, and then the fans installed therein are operated for 1 day to attach the fine dust to the filters, and then the contaminated filters are distilled.
  • the total heavy metal amount (Cu, Zn, Mn, Ni, Cd) of the fine dust aqueous solution was measured using a total heavy metal test kit (WAK-Me TM , Kyoritsu Chemical-Check Lab., Japan). Did.
  • the measurement of the total heavy metal amount is shown in Table 2 by comparing the color development of the aqueous solution with the standard color.
  • Example 13 Trientine ⁇ 5 (red)
  • Example 14 Example 1 ⁇ 5 Example 15
  • Example 2 ⁇ 5
  • Example 16 Example 3 ⁇ 5
  • Example 17 Example 4
  • Example 18 Cyclen ⁇ 5
  • Example 19 Example 5 ⁇ 5
  • Example 20 Example 6 ⁇ 5
  • Example 21 Example 7 ⁇ 5
  • Example 22 Example 8 ⁇ 5
  • Example 23 Cyclam ⁇ 5
  • Example 24 Example 9 ⁇ 5
  • Example 25 Example 10 ⁇ 5 Example 26
  • Example 12 ⁇ 5 Comparative Example 1 - 2.0
  • the first stimulation test for human skin was conducted by the method of patching according to the guidelines of CTFA (The Cosmetic, Toiletry & Fragrance Association.Inc. It was carried out.
  • the heavy metal chelating agent compound according to the embodiment of the present invention showed a class I in the irritation range up to 0.5 wt% concentration range in the human skin irritation experiment, and triene in the 1.0 wt% concentration range While tin, cyclin, and cyclam showed grade II (light stimulation range), their aromatic and heterocyclic derivatives all showed grade I, suggesting that skin irritation reduction is improved.
  • EDTA of Comparative Example 1 was determined to be grade III (medium irritation range) at a concentration of 1.0% by weight, indicating that the skin irritation was higher than that of the compound of the present invention. Therefore, it can be seen that the filter according to the present invention is harmless to the human body and can be used for a cigarette filter or an air mask.
  • Trientine, cyclene, cyclam, and trientine derivatives, cycline derivatives, and cyclam derivatives prepared in Examples 1 to 12 were prepared as 0.5%, 1.0%, and 2.0% aqueous solutions, respectively, and sold commercially.
  • a tobacco filter containing the active ingredient of the present invention was prepared by purchasing the tobacco to be impregnated with the aqueous solution in the lower quarter of the tobacco filter for 4 seconds, and then drying the active ingredient of the present invention for 1 hour. .
  • Table 4 shows the active ingredients of the cigarette filter.
  • Example 28 Trientine Example 29
  • Example 1 Example 30
  • Example 2 Example 31
  • Example 3 Example 32
  • Example 4 Example 33 Cyclen
  • Example 34 Example 5
  • Example 6 Example 36
  • Example 7 Example 37
  • Example 8 Example 38 Cyclam
  • Example 9 Example 40
  • Example 10 Example 41
  • Example 11 Example 42
  • Example 12 Comparative Example 2 -
  • Filter cigarettes containing the active ingredient prepared in Example 2 were prepared as a sample of 4 samples per active ingredient, placed in an inhalation device set to conditions similar to actual smoking, lighted, and then activated the inhalation device. Smoking was conducted.
  • the smoked cigarette filters were collected, and each sample (one set of 4 skins) was put into 100 ml of methanol, extracted by ultrasonic shaking for 60 minutes, cooled to room temperature, and then put into methanol to make 100 ml, and then 30 ml of samples with the filter removed It concentrated to the extent to prepare a test solution.
  • the prepared sample was analyzed for the heavy metal component using an inductively coupled plasma mass spectrometer (ICP-MS, Inductively Coupled Plasma Mass Spectrometer) (Xseries TM 2, Thermo Fisher Scientific, UK).
  • ICP-MS Inductively Coupled Plasma Mass Spectrometer
  • Heavy metal adsorption rate (%) (Example of heavy metal adsorption/control metal heavy adsorption) ⁇ 100
  • the adsorption rate of arsenic (Pb) of the cigarette filter containing the heavy metal chelating agent compound according to the embodiment of the present invention is about 148 to 274%, and the cadmium (Cd) adsorption rate is 129 to The adsorption rate of 213% and nickel (Ni) is 117 to 191%, and it can be seen that the heavy metal adsorption rate increases significantly as the content of the active ingredient increases. This is effective for the cigarette filter containing the active ingredient according to the present invention. It means that it has a remarkably superior ability to remove heavy metals compared to a non-component tobacco filter.
  • the content of formaldehyde was performed under the following analytical conditions, and the content of formaldehyde after initial, 30 minutes, and 180 minutes is shown in Table 6.
  • Example 1 0.305 0.170 0
  • Example 2 0.305 0.168 0
  • Example 3 0.305 0.171 0
  • Example 4 0.305 0.173 0 Cyclen 0.305 0.181 0
  • Example 5 0.305 0.179 0
  • Example 6 0.305 0.183 0
  • Example 7 0.305 0.181 0
  • Example 8 0.305 0.168 0 Cyclam 0.305 0.172 0
  • Example 9 0.305 0.182 0
  • Example 10 0.305 0.171 0
  • Example 11 0.305 0.174 0
  • Example 12 0.305 0.170 0
  • the present invention relates to a filter for effectively removing heavy metals and formaldehyde, and more particularly, to an air filter, a cigarette filter, and an air mask that can be used in various air conditioning systems such as household and automobile air purifiers and air conditioners.

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  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Combustion & Propulsion (AREA)
  • Textile Engineering (AREA)
  • Physical Education & Sports Medicine (AREA)
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Abstract

The present invention provides a filter having heavy metal and formaldehyde removal capability, comprising, as an active ingredient, at least one selected from among trientine or a trientine derivative represented by the following chemical formula 1, cyclen or a cyclen derivative represented by the following chemical formula 2, and cyclam or a cyclam derivative represented by the following chemical formula 3.

Description

중금속 및 포름알데히드 제거능을 가지는 필터Filter for removing heavy metals and formaldehyde
본 발명은 중금속과 포름알데히드를 효과적으로 제거하기 위한 필터에 관한 것으로, 보다 상세히는 가정용·자동차용 공기청정기, 에어컨 등의 다양한 공조시스템에 이용될 수 있는 공기 필터, 담배 필터, 공기마스크에 관한 것이다.The present invention relates to a filter for effectively removing heavy metals and formaldehyde, and more particularly, to an air filter, a cigarette filter, and an air mask that can be used in various air conditioning systems such as household and automobile air purifiers and air conditioners.
오늘날 대기오염에 따른 미세먼지 발생이 나날이 증가하고 있어 환경 문제로 대두되고 있다. 미세먼지 차단을 위해 외출시 공기 마스크의 착용은 이제 보편화되는 추세에 있고, 실내 공기 정화를 위해 크고 작은 다양한 공기청정기가 판매되고 있고, 아파트와 같은 주택 건설시 각종 필터가 장착된 환기시스템이 도입되고 있는 실정이다.Today, the occurrence of fine dust due to air pollution is increasing day by day, and is becoming an environmental problem. In order to block fine dust, wearing of an air mask when going out is now becoming common, various air purifiers are sold for large and small to purify indoor air, and ventilation systems equipped with various filters are introduced when building houses such as apartments. That is true.
미세먼지(PM10)는 평균 입경 10㎛ 이하, 초미세먼지(PM2.5)는 평균 입경 2.5㎛ 이하의 먼지로서 천식, 폐 기능 저하 등 각종 호흡기 질환과 피부염, 알레르기, 아토피 등 각종 피부 질환을 일으키는 요인으로 알려져 있다.Fine dust (PM 10 ) is dust with an average particle diameter of 10 μm or less, and ultrafine dust (PM 2.5 ) is dust with an average particle size of 2.5 μm or less, causing various respiratory diseases such as asthma and lung function, and various skin diseases such as dermatitis, allergies and atopy. It is known as a factor.
미세먼지에는 지역, 환경, 계절 등에 따라 차이가 있으나 Hg(수은), Pb(납), Cd(카드뮴), As(비소), Cr(크롬), Cu(구리), Ni(니켈), Zn(아연), Mn(망간), Co(코발트), Sn(주석) 등 유해 중금속이 약 20% 정도로 다량 함유되어 각종 질환을 유발하는 것으로 보고되어 있다.Fine dust varies depending on the region, environment, and season, but Hg (mercury), Pb (lead), Cd (cadmium), As (arsenic), Cr (chrome), Cu (copper), Ni (nickel), and Zn ( Zinc), Mn (manganese), Co (cobalt), Sn (tin), etc., contains about 20% of harmful heavy metals, and is reported to cause various diseases.
이러한 미세먼지, 중금속을 제거하기 위하여 시스템에 맞게 다양한 소재, 규격의 필터들이 개발되고, 판매되고 있다. 이러한 필터는 집진방식에 따라 여과식, 정전식, 충돌점착식, 흡착식 필터, 집진입경에 따라 조진용, 중진용, 미진용, 가스제거용 필터 등으로 구분되는 데, 단일 필터 뿐만 아니라 여러 종류의 필터를 겹쳐 제작된 복합 필터들이 이용되고 있다.In order to remove such fine dust and heavy metals, filters of various materials and standards are developed and sold according to the system. These filters are classified into filtration type, electrostatic type, collision adhesion type, adsorption type filter, and dust type, medium size, fine size, and gas removal type filters according to the dust collection method. Composite filters produced by overlapping are used.
필터의 소재로는 종이 필터, 부직포 필터, 염화비닐 필터, 헤파(HEPA)필터와 카본, 활성탄, 제오라이트, 실리카겔, 알루미나, 산화제2철 등 각종 흡착제가 첨가된 소재 등이 있으나, 이들 소재들은 미세먼지 특히 중금속과 1급 발암물질인 포름알데히드의 흡착성능이 아직 만족할 만한 수준에 있지는 않다. 헤파(HEPA)필터는 등급에 따라 0.3㎛ 이하의 미세먼지까지 제거할 수 있으나, 그 비용 비싸고 중금속, 포름알데히드의 흡착성능 역시 아직 한계가 있다.Filter materials include paper filters, nonwoven filters, vinyl chloride filters, HEPA filters and carbon, activated carbon, zeolite, silica gel, alumina, ferric oxide, and other adsorbents. In particular, the adsorption performance of heavy metals and formaldehyde, a primary carcinogen, is not yet satisfactory. The HEPA filter can remove fine dust of 0.3 µm or less depending on the grade, but the cost is high and the adsorption performance of heavy metals and formaldehyde is still limited.
한편, As(비소), 카듀믐(Cd), Ni(니켈) 등과 같은 유해 중금속들은 미세먼지 외에도 연초(담배) 성분에 포함되어 있어 흡연시 니코틴, 티르, 유해 가스와 함께 호흡기로 유입되어 폐암과 같은 질병을 유발하는 것으로 알려져 있다. 일반적인 담배는 흡연시 중 타르 및 니코틴, 일산화탄소 등을 거르기 위해 아세테이트 토우(Acetate Tow) 섬유 소재 담배필터가 있고, 필터 성능을 증가시키기 위하여 다공성 흡착제인 활성탄 또는 제오라이트 등이 첨가된 것이 있다. 그러나 이와 같은 활성탄과 제오라이트는 니코틴이나 타르 제거에는 어느 정도 효과가 있으나, 중금속, 포름알데히드 등의 흡착 제거에는 큰 효과가 없다.On the other hand, harmful heavy metals such as As (arsenic), Kaduchen (Cd), and Ni (nickel) are included in the tobacco (cigarette) component in addition to fine dust, and when they smoke, they enter the respiratory tract with nicotine, tyr, and harmful gases, causing lung cancer and It is known to cause the same disease. Common cigarettes are cigarette filters made of acetate tow fibers to filter tar, nicotine, and carbon monoxide during smoking, and there are added porous adsorbents such as activated carbon or zeolite to increase filter performance. However, such activated carbon and zeolite have a certain effect on the removal of nicotine or tar, but have no great effect on adsorption and removal of heavy metals and formaldehyde.
본 발명은 상기와 같은 문제를 해결하기 위한 것으로, 중금속과 포름알데히드를 효과적으로 제거할 수 있는 공기 필터 소재를 제공하고, 이러한 필터를 이용하여 공기청정기, 에어컨, 공기순환시스템 등 각종 공조장치에 이용될 수 있는 공기 필터, 담배 필터, 공기 마스크를 제공하는 데 그 목적이 있다.The present invention is to solve the above problems, provides an air filter material that can effectively remove heavy metals and formaldehyde, and can be used in various air conditioning devices such as air cleaners, air conditioners, and air circulation systems using these filters. The purpose is to provide an air filter, a cigarette filter, and an air mask.
상기 목적을 달성하기 위하여 본 발명은, 중금속과 포름알데히드 제거를 위한 유효성분으로 하기 화학식 1로 표시되는 트리엔틴 또는 트리엔틴 유도체, 하기 화학식 2로 표시되는 사이클렌 또는 사이클렌 유도체, 하기 화학식 3으로 표시되는 사이클람 또는 사이클람 유도체 중에서 선택된 1종 이상을 포함하는, 중금속 및 포름알데히드 제거능을 가지는 필터를 제공한다.In order to achieve the above object, the present invention is a trientine or a trientine derivative represented by the following Chemical Formula 1, a cyclene or cyclene derivative represented by the following Chemical Formula 2 as an active ingredient for removing heavy metals and formaldehyde, the following Chemical Formula It provides a filter having a heavy metal and formaldehyde removal ability, including at least one selected from a cyclam or a cyclam derivative represented by 3.
[화학식 1][Formula 1]
Figure PCTKR2018016802-appb-I000001
Figure PCTKR2018016802-appb-I000001
[화학식 2][Formula 2]
Figure PCTKR2018016802-appb-I000002
Figure PCTKR2018016802-appb-I000002
[화학식 3][Formula 3]
Figure PCTKR2018016802-appb-I000003
Figure PCTKR2018016802-appb-I000003
(상기 식들에서, R1, R2, R3, R4, R5 및 R6은 각각 독립적으로 수소, -R7-COOH 또는 이들의 염이고, R7은 C1~C5의 지방족, 치환되거나 치환되지 않은 방향족 고리, 또는 복소환 6원자 또는 5원자 고리이다.)(In the above formula, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen, -R 7 -COOH or a salt thereof, R 7 is C 1 ~C 5 aliphatic, A substituted or unsubstituted aromatic ring, or a heterocyclic 6-membered or 5-membered ring.)
상기 유효성분은 하기 화학식 1a의 트리엔틴, 화학식 2a의 사이클렌, 화학식 3a의 사이클람 또는 이들의 염 중에서 선택되는 것이 바람직하다.The active ingredient is preferably selected from trientine of the following formula 1a, cyclene of the formula 2a, cyclam of the formula 3a or salts thereof.
[화학식 1a][Formula 1a]
Figure PCTKR2018016802-appb-I000004
Figure PCTKR2018016802-appb-I000004
[화학식 2a][Formula 2a]
Figure PCTKR2018016802-appb-I000005
Figure PCTKR2018016802-appb-I000005
[화학식 3a][Formula 3a]
Figure PCTKR2018016802-appb-I000006
Figure PCTKR2018016802-appb-I000006
상기 트리엔틴 유도체는 하기 화학식 1b 내지 1d로 표시되는 화합물 또는 이들의 염 중에서 선택되는 것이 바람직하다.The trientine derivative is preferably selected from compounds represented by the following formulas 1b to 1d or salts thereof.
[화학식 1b][Formula 1b]
Figure PCTKR2018016802-appb-I000007
Figure PCTKR2018016802-appb-I000007
[화학식 1c][Formula 1c]
Figure PCTKR2018016802-appb-I000008
Figure PCTKR2018016802-appb-I000008
[화학식 1d][Formula 1d]
Figure PCTKR2018016802-appb-I000009
Figure PCTKR2018016802-appb-I000009
(상기 식들에서, R8, R9는 각각 독립적으로 수소 또는 C1~C4의 알킬기이고, X는 산소(O), 황(S) 또는 질소(N)이다.)(In the above formulas, R 8 and R 9 are each independently hydrogen or an alkyl group of C 1 to C 4 , and X is oxygen (O), sulfur (S) or nitrogen (N).)
상기 사이클렌 유도체는 하기 화학식 2b 내지 2d로 표시되는 화합물 또는 이들의 염 중에서 선택되는 것이 바람직하다.The cyclone derivative is preferably selected from compounds represented by the following formulas 2b to 2d or salts thereof.
[화학식 2b][Formula 2b]
Figure PCTKR2018016802-appb-I000010
Figure PCTKR2018016802-appb-I000010
[화학식 2c][Formula 2c]
Figure PCTKR2018016802-appb-I000011
Figure PCTKR2018016802-appb-I000011
[화학식 2d][Formula 2d]
Figure PCTKR2018016802-appb-I000012
Figure PCTKR2018016802-appb-I000012
(상기 식들에서, R8, R9는 각각 독립적으로 수소 또는 C1~C4의 알킬기이고, X는 산소(O), 황(S) 또는 질소(N)이다.)(In the above formulas, R 8 and R 9 are each independently hydrogen or an alkyl group of C 1 to C 4 , and X is oxygen (O), sulfur (S) or nitrogen (N).)
상기 사이클람 유도체는 하기 화학식 3b 내지 3d로 표시되는 화합물 또는 이들의 염 중에서 선택되는 것이 바람직하다.The cyclam derivative is preferably selected from compounds represented by the following formulas 3b to 3d or salts thereof.
[화학식 3b][Formula 3b]
Figure PCTKR2018016802-appb-I000013
Figure PCTKR2018016802-appb-I000013
[화학식 3c][Formula 3c]
Figure PCTKR2018016802-appb-I000014
Figure PCTKR2018016802-appb-I000014
[화학식 3d][Formula 3d]
Figure PCTKR2018016802-appb-I000015
Figure PCTKR2018016802-appb-I000015
(상기 식들에서, R8, R9는 각각 독립적으로 수소 또는 C1~C4의 알킬기이고, X는 산소(O), 황(S) 또는 질소(N)이다.)(In the above formulas, R 8 and R 9 are each independently hydrogen or an alkyl group of C 1 to C 4 , and X is oxygen (O), sulfur (S) or nitrogen (N).)
본 발명에 따른 유효성분을 함유하는 필터는 미세먼지에 존재하는 중금속을 제거하는 데 효과가 탁월하여, 공기청정기, 에어컨, 공기순환시스템 등 각종 공조장치에 이용될 수 있는 공기 필터, 담배 필터, 공기 마스크 소재로 유용하게 이용될 수 있다.The filter containing the active ingredient according to the present invention is excellent in removing heavy metals present in fine dust, and air filters, cigarette filters, and air that can be used in various air conditioning devices such as air cleaners, air conditioners, and air circulation systems It can be usefully used as a mask material.
본 발명에 있어서, "필터"는 공기청정기, 에어컨, 공기순환시스템 등 각종 공조장치에 이용될 수 있는 공기 필터는 물론 담배 필터, 공기 마스크용 필터를 포함한다.In the present invention, the "filter" includes an air filter that can be used in various air conditioning apparatuses such as an air purifier, an air conditioner, and an air circulation system, as well as a cigarette filter and a filter for an air mask.
본 발명자들은 중금속과 1급 발암 물질인 포름알데히드를 효과적으로 제거할 수 있는 필터 소재를 개발하기 위하여 중금속 킬레이트제에 대해 다양한 연구를 수행하였고, 현재 의약품으로 이용되고 있는 트리엔틴, 사이클렌, 사이클람과 이들의 유도체를 필터의 중금속, 포름알데히드 흡착제로 이용시 그 제거능이 현저히 우수수한 것으로 확인하여 본 발명에 이르렀다.The present inventors have conducted various studies on heavy metal chelating agents to develop filter materials that can effectively remove heavy metals and formaldehyde, which is a primary carcinogen, and are currently used as pharmaceuticals, trientine, cyclene, and cyclam. When these and their derivatives are used as heavy metal and formaldehyde adsorbents of filters, it has been confirmed that the removal ability is remarkably excellent, leading to the present invention.
트리엔틴(trientine)은 하기 화학식 1a로 표시되며, Triethylenetetramine(TETA)로 명칭된다.Trientine (trientine) is represented by the following formula 1a, it is called Triethylenetetramine (TETA).
[화학식 1a][Formula 1a]
Figure PCTKR2018016802-appb-I000016
Figure PCTKR2018016802-appb-I000016
트리엔틴 중염산염(Triethylenetetramine dihydrochloride)는 생쥐실험에서 구리(copper)의 대사에 관여하는 것이 밝혀졌으며(F. W. Sunderman et al., Toxicol. Appl . Pharmacol. 38, 177 (1976)), 약리적으로는 구리에 대한 킬레이트제로 작용하여 윌슨병(Wilson's disease) 치료제로 잘 알려져 있다(J. M. Walshe, Prog. Clin . Biol. Res. 34, 271 (1979); R. H. Haslam et al., Dev . Pharmacol . Ther. 1, 318 (1980)).Hydrochloride (Triethylenetetramine dihydrochloride) of triene tin has been found to be involved in the metabolism of copper (copper) in the rat experiment (FW Sunderman et al., Toxicol . Appl. Pharmacol. 38, 177 (1976)), pharmacological as copper Acting as a chelating agent for Wilson's disease, it is well known as a treatment agent (JM Walshe, Prog. Clin . Biol . Res. 34, 271 (1979); RH Haslam et al., Dev . Pharmacol . Ther . 1, 318 (1980)).
사이클렌(Cyclen)은 하기 화학식 2a로 표시되는 1,4,7,10-tetraazacyclododecane의 일반명으로, 가돌리늄(Gd)과 배위결합을 통해 킬레이트를 형성하여 핵의학 조영제 등에 이용되고 있다.Cyclen (Cyclen) is a general name of 1,4,7,10-tetraazacyclododecane represented by the following Chemical Formula 2a, and is used in nuclear medicine contrast agents by forming chelates through coordination with gadolinium (Gd).
[화학식 2a][Formula 2a]
Figure PCTKR2018016802-appb-I000017
Figure PCTKR2018016802-appb-I000017
사이클람(Cyclam)은 하기 화학식 3a로 표시되는 1,4,8,11-tetraazacyclotetradecane의 일반명으로 핵의학 조영제 등에 이용되고 있다.Cyclam (Cyclam) is a general name of 1,4,8,11-tetraazacyclotetradecane represented by the following Chemical Formula 3a and is used in nuclear medicine contrast media.
[화학식 3a][Formula 3a]
Figure PCTKR2018016802-appb-I000018
Figure PCTKR2018016802-appb-I000018
상기 트리엔틴, 사이클렌, 사이클람과 같은 킬레이트제들은 경구 또는 혈관 투여 방법을 통하여 체내의 구리 배출하거나 조영제 재료로서의 의약적 용도는 잘 알려져 있으나, 필터 재료로의 용도 연구는 보고된 바 없다.Chelating agents such as trientine, cyclene, and cyclam are well known for medicinal use of copper as a contrast material or to release copper from the body through oral or vascular administration methods, but no research on its use as a filter material has been reported.
본 발명에 이르러 트리엔틴, 사이클렌, 사이클람 화합물이 중금속 제거를 위한 필터 성분으로 유용함이 확인되었다. 본 발명에서 필터 소재로서 미세먼지 속 중금속 제거능과 피부 자극, 독성에 대한 결과가 개시된다. 트리엔틴, 사이클렌, 사이클람 화합물은 종래 피부에 유해한 것으로 알려져 있으나, 본 발명의 실험 결과 피부 상의 중금속 제거에 효과적인 양의 사용에서는 피부 자극 또는 독성이 없거나 필터 재료로서 허용될 수 있는 정도로 매우 낮은 것이 확인되었다.It has been confirmed that the trientine, cyclene, and cyclam compounds are useful as filter components for removing heavy metals. In the present invention, as a filter material, results for removal of heavy metals in fine dust, skin irritation, and toxicity are disclosed. Trientine, cyclene, and cyclam compounds are known to be harmful to conventional skin, but the experimental results of the present invention show no skin irritation or toxicity in the use of an amount effective to remove heavy metals on the skin, or very low as acceptable as a filter material. Was confirmed.
한편, 본 발명에 이르러 트리엔틴, 사이클렌, 사이클람과 이들의 유도체 화합물이 1급 발암물질인 포름알데히드의 제거에 매우 효과적인 것이 확인되었다.On the other hand, it has been found that trientine, cyclene, cyclam and their derivatives are very effective in the removal of formaldehyde, a primary carcinogen, in the present invention.
본 발명은 하기 화학식 1로 표시되는 트리엔틴 또는 트리엔틴 유도체, 하기 화학식 2로 표시되는 사이클렌 또는 사이클렌 유도체, 하기 화학식 3으로 표시되는 사이클람 또는 사이클람 유도체 중에서 선택된 1종 이상을 유효성분으로 하는, 중금속 및 포름알데히드 제거능을 가지는 필터를 제공한다.The present invention is effective for at least one selected from trientine or trientine derivatives represented by the following Chemical Formula 1, cyclene or cyclene derivatives represented by the following Chemical Formula 2, cyclam or cyclam derivatives represented by the following Chemical Formula 3 Provided is a filter having a heavy metal and formaldehyde removal ability as a component.
[화학식 1][Formula 1]
Figure PCTKR2018016802-appb-I000019
Figure PCTKR2018016802-appb-I000019
[화학식 2][Formula 2]
Figure PCTKR2018016802-appb-I000020
Figure PCTKR2018016802-appb-I000020
[화학식 3][Formula 3]
Figure PCTKR2018016802-appb-I000021
Figure PCTKR2018016802-appb-I000021
(상기 식들에서, R1, R2, R3, R4, R5 및 R6은 각각 독립적으로 수소, -R7-COOH 또는 이들의 염이고, R7은 C1~C5의 지방족, 치환되거나 치환되지 않은 방향족 고리, 또는 복소환 6원자 또는 5원자 고리이다.)(In the above formula, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen, -R 7 -COOH or a salt thereof, R 7 is C 1 ~C 5 aliphatic, A substituted or unsubstituted aromatic ring, or a heterocyclic 6-membered or 5-membered ring.)
본 발명의 공기 필터는 중금속 및 포름알데히드 제거를 위한 유효성분으로 트리엔틴, 사이클렌, 사이클람 또는 이들의 염을 포함하는 것을 특징으로 한다.The air filter of the present invention is characterized in that it contains trientine, cyclene, cyclam or salts thereof as an active ingredient for removing heavy metals and formaldehyde.
한편, 본 발명에서 상기 트리엔틴, 사이클렌, 사이클람 화합물의 아민 위치에 카르복실기를 도입하여 중금속 배위결합도를 향상시키는 한편, 방향족 또는 복소환기를 도입하는 경우 피부 자극이 현저히 저감되는 것이 확인되었다.On the other hand, in the present invention, by introducing a carboxyl group at the amine position of the trientine, cyclin, and cyclam compounds to improve the degree of coordination of heavy metals, it was confirmed that when introducing an aromatic or heterocyclic group, skin irritation is significantly reduced. .
본 발명에 따른 트리엔틴 유도체, 사이클렌 유도체, 사이클람 유도체는 하기 화학식 1b 내지 3d로 표시되는 화합물에서 선택되는 것이 바람직하다.It is preferable that the trientine derivative, the cyclene derivative, and the cyclam derivative according to the present invention are selected from compounds represented by the following formulas 1b to 3d.
[화학식 1b][Formula 1b]
Figure PCTKR2018016802-appb-I000022
Figure PCTKR2018016802-appb-I000022
[화학식 1c][Formula 1c]
Figure PCTKR2018016802-appb-I000023
Figure PCTKR2018016802-appb-I000023
[화학식 1d][Formula 1d]
Figure PCTKR2018016802-appb-I000024
Figure PCTKR2018016802-appb-I000024
[화학식 2b][Formula 2b]
Figure PCTKR2018016802-appb-I000025
Figure PCTKR2018016802-appb-I000025
[화학식 2c][Formula 2c]
Figure PCTKR2018016802-appb-I000026
Figure PCTKR2018016802-appb-I000026
[화학식 2d][Formula 2d]
Figure PCTKR2018016802-appb-I000027
Figure PCTKR2018016802-appb-I000027
[화학식 3b][Formula 3b]
Figure PCTKR2018016802-appb-I000028
Figure PCTKR2018016802-appb-I000028
[화학식 3c][Formula 3c]
Figure PCTKR2018016802-appb-I000029
Figure PCTKR2018016802-appb-I000029
[화학식 3d][Formula 3d]
Figure PCTKR2018016802-appb-I000030
Figure PCTKR2018016802-appb-I000030
(상기 식들에서, R8, R9는 각각 독립적으로 수소 또는 C1~C4의 알킬기이고, X는 산소(O), 황(S) 또는 질소(N)이다.)(In the above formulas, R 8 and R 9 are each independently hydrogen or an alkyl group of C 1 to C 4 , and X is oxygen (O), sulfur (S) or nitrogen (N).)
본 발명의 트리엔틴 또는 트리엔틴 유도체, 사이클렌 또는 사이클렌 유도체, 사이클람 또는 사이클람 유도체 화합물은 필터의 용도, 소재에 따라 그 함량은 변경가능하다. 본 발명의 유효성분은 유효성분이 함유된 필터 중량에 대하여 제한되지는 않으나 0.001 ~ 5.0 중량%, 바람직하게는 0.1 ~ 3.0 중량%, 더욱 바람직하게는 0.2 ~ 2.0 중량%로 함유될 수 있다.The content of the trientine or trientine derivative, cyclene or cyclene derivative, cyclam or cyclam derivative compound of the present invention can be changed depending on the use and material of the filter. The active ingredient of the present invention is not limited to the weight of the filter containing the active ingredient, but may be contained in 0.001 to 5.0% by weight, preferably 0.1 to 3.0% by weight, more preferably 0.2 to 2.0% by weight.
본 발명의 트리엔틴 또는 트리엔틴 유도체, 사이클렌 또는 사이클렌 유도체, 사이클람 또는 사이클람 유도체 화합물는 수용성 염의 형태로 이용될 수 있다. 본 발명의 상기 화합물은 염산염, 나트륨염, 칼륨염의 형태를 포함한다. 본 발명의 상기 화합물은 이염산염, 사염산염의 형태인 것이 더욱 바람직하다. 상기 염의 제조는 공지의 방법에 의해 수행될 수 있다.The trientine or trientine derivatives of the present invention, cyclene or cyclic derivatives, cyclam or cyclam derivative compounds may be used in the form of water-soluble salts. The compounds of the present invention include the form of hydrochloride, sodium salt, potassium salt. More preferably, the compound of the present invention is in the form of dihydrochloride or tetrachloride. Preparation of the salt can be performed by a known method.
본 발명의 필터는 상기 유효성분을 수용액 또는 용액 형태로 제조하고, 종래 이용되는 필터 소재에 함침시키거나, 스프레이 방식으로 분사시킨 후 건조하는 방식으로 제조될 수 있다. 본 발명의 필터 소재는 종이 필터, 부직포 필터, 섬유 필터, 염화비닐 필터, 헤파(HEPA)필터, 카본, 활성탄, 제오라이트, 실리카겔, 알루미나, 산화제2철 등 각종 흡착제가 첨가된 필터 소재 등 통상적으로 사용되는 필터 소재일 수 있다.The filter of the present invention may be prepared by preparing the active ingredient in the form of an aqueous solution or a solution, impregnating the filter material used conventionally, or spraying it and drying it. The filter material of the present invention is commonly used as a filter material to which various adsorbents such as paper filter, nonwoven filter, fiber filter, vinyl chloride filter, HEPA filter, carbon, activated carbon, zeolite, silica gel, alumina, ferric oxide, etc. are added. It may be a filter material.
본 발명의 필터는 단일 필터로 이용될 수 있으며, 다른 필터 소재와 겹친 형태의 복합 필터로 이용될 수 있다.The filter of the present invention may be used as a single filter, or may be used as a composite filter overlapping other filter materials.
이하 실시예를 통하여 본 발명의 중금속 및 포름알데히드 제거능을 가지는 필터를 상세히 설명한다. 다만, 하기 실시예는 본 발명의 일 예시일 뿐 하기 실시예로 본 발명의 청구범위가 제한되지는 않는다.Hereinafter, a filter having a heavy metal and formaldehyde removal ability of the present invention will be described in detail through examples. However, the following examples are only examples of the present invention and the claims of the present invention are not limited to the following examples.
<트리엔틴 유도체의 합성><Synthesis of trientine derivatives>
실시예Example 1: 31: 3 ,6,9,12-,6,9,12- tetrakistetrakis (( carboxymethylcarboxymethyl )-3,6,9,12-tetraazatetradecanedioic acid (화학식 1e)의 제조)-3,6,9,12-tetraazatetradecanedioic acid (Formula 1e) Preparation
Figure PCTKR2018016802-appb-I000031
Figure PCTKR2018016802-appb-I000031
Triethylenetetramine 10.0g과 아세토니트릴(ACN) 400.0ml를 투입 교반하고 K2CO3 66.1g과 Ethyl bromoacetate 78.8g을 투입하고 승온하여 48시간 환류교반하여 반응을 종결한다. 상온으로 냉각하여 여과하여 고체는 폐기하고 여액은 진공 농축한다. 농축액에 메틸렌 클로라이드(MC) 200ml, 정제수 300ml 투입후 30분간 교반후 정치하여 층분리한다. 유기층은 MgSO4 처리하여 진공 농축 후 MC-MeOH로 컬럼정제하여 Diethyl 3,6,9,12-tetrakis(2-ethoxy-2-oxoethyl)-3,6,9,12-tetraazatetradecanedioate 29.6g을 수득하였다.(수율: 64.8%)10.0 g of triethylenetetramine and 400.0 ml of acetonitrile (ACN) were added and stirred, 66.1 g of K 2 CO 3 and 78.8 g of ethyl bromoacetate were added, heated to reflux and stirred for 48 hours to terminate the reaction. Cool to room temperature, filter, discard the solid, and concentrate the filtrate in vacuo. After adding 200 ml of methylene chloride (MC) and 300 ml of purified water to the concentrate, the mixture was stirred for 30 minutes and left to separate. The organic layer is MgSO 4 After treatment, concentrated in vacuo and purified by MC-MeOH to obtain 29.6 g of Diethyl 3,6,9,12-tetrakis(2-ethoxy-2-oxoethyl)-3,6,9,12-tetraazatetradecanedioate (yield: 64.8%)
1H NMR (CDCl3): 4.16(q, 8H), 4.14(q, 4H), 3.57(s, 8H), 3.44(s, 4H), 2.85(t, 4H), 2.78(t, 4H), 2.74(s, 4H), 1.27(t, 12H), 1.26(t, 6H) 1 H NMR (CDCl 3 ): 4.16 (q, 8H), 4.14 (q, 4H), 3.57 (s, 8H), 3.44 (s, 4H), 2.85 (t, 4H), 2.78 (t, 4H), 2.74(s, 4H), 1.27(t, 12H), 1.26(t, 6H)
상기 제조된 Diethyl 3,6,9,12-tetrakis(2-ethoxy-2-oxoethyl)-3,6,9,12-tetraazatetradecanedioate 29.6g과 NaOH 12.33g, MeOH 180ml, 정제수 120ml를 투입하고 55~60℃로 승온하여 12시간 교반하여 반응을 종결한다. 40℃로 냉각하고 진공 농축하여 용매를 제거하고 10% HCl 수용액으로 pH를 5~6로 맞추고 30분간 교반한다. MC 400ml를 투입하여 추출한다. 추출한 유기층은 MgSO4 처리하여 표제 화합물 15.9g을 수득하였다.(수율: 72.3.0%)The prepared Diethyl 3,6,9,12-tetrakis(2-ethoxy-2-oxoethyl)-3,6,9,12-tetraazatetradecanedioate 29.6g and NaOH 12.33g, MeOH 180ml, purified water 120ml were added and 55-60 The reaction was terminated by heating to ℃ and stirring for 12 hours. After cooling to 40°C and concentrating in vacuo to remove the solvent, adjust the pH to 5-6 with 10% aqueous HCl and stir for 30 minutes. MC 400ml is added to extract. The extracted organic layer was treated with MgSO 4 to obtain 15.9 g of the title compound. (Yield: 72.3.0%)
1H NMR (DMSO): 4.57(s, 8H), 4.55(s, 4H), 4.22(s, 12H) 1 H NMR (DMSO): 4.57 (s, 8H), 4.55 (s, 4H), 4.22 (s, 12H)
실시예Example 2: 42: 4 ,4',4'',4'''-(,4',4'',4'''-( ((ethane-1,2-diylbis(((ethane-1,2-diylbis( (4-carboxyphenyl)azanediyl))bis(ethane-2,1-diyl))bis(azanetriyl))tetrabenzoic acid (화학식 1f)의 제조Preparation of (4-carboxyphenyl)azanediyl))bis(ethane-2,1-diyl))bis(azanetriyl))tetrabenzoic acid (Formula 1f)
Figure PCTKR2018016802-appb-I000032
Figure PCTKR2018016802-appb-I000032
트리에틸렌테트라민 10.0g, ethyl 4-bromobenzoate 108,1g, t-BuONa 46.0g과 toluene 600ml를 투입 교반한다. 35℃로 승온하여 50% (t-Bu)3P toluene solution 2.8g을 투입하고 30분간 교반하고 50℃로 승온한 후 Pd(dba)2 2.0g을 투입하고 승온하여 환류교반하여 반응을 종결한다. 상온으로 냉각하여 정제수 1000ml를 투입하고 30분간 교반 정치하여 층분리하여 수층은 폐기한다. 유기층은 MgSO4 처리하여 진공 농축 후 MC-MeOH 컬럼 정제하여 tetraethyl 4,4',4'',4'''-(((ethane-1,2-diylbis((4-(ethoxycarbonyl)phenyl)azanediyl)) bis(ethane-2,1-diyl))bis(azanetriyl))tetrabenzoate 22.9g을 수득 하였다. (수율: 32.4%)Triethylenetetramine 10.0g, ethyl 4-bromobenzoate 108,1g, t-BuONa 46.0g and toluene 600ml were added and stirred. After heating up to 35°C, 2.8g of 50% (t-Bu) 3 P toluene solution was added, stirred for 30 minutes, heated to 50°C, and then 2.0g of Pd(dba)2 was added and heated to reflux stirring to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer. The organic layer was treated with MgSO 4 and concentrated in vacuo, and then purified by MC-MeOH column to tetraethyl 4,4',4'',4'''-(((ethane-1,2-diylbis((4-(ethoxycarbonyl)phenyl)azanediyl )) bis(ethane-2,1-diyl))bis(azanetriyl))tetrabenzoate 22.9g was obtained. (Yield 32.4%)
1H NMR (CDCl3): 7.82(m, 4H), 7.71(m, 8H), 7.25(m, 8H), 6.95(m, 4H), 4.15(q, 8H), 4.11(q, 4H), 3.45~3.18(m, 12H), 1.27(t, 12H), 1.26(t, 6H) 1 H NMR (CDCl 3 ): 7.82 (m, 4H), 7.71 (m, 8H), 7.25 (m, 8H), 6.95 (m, 4H), 4.15 (q, 8H), 4.11 (q, 4H), 3.45~3.18(m, 12H), 1.27(t, 12H), 1.26(t, 6H)
tetraethyl 4,4',4'',4'''-(((ethane-1,2-diylbis((4-(ethoxycarbonyl)phenyl)azanediyl)) bis(ethane-2,1-diyl))bis(azanetriyl))tetrabenzoate 22.9g과 NaOH 6.1g, MeOH 180ml, 정제수 140ml를 투입하고 55~60℃로 승온하여 12시간 교반하여 반응을 종결한다. 40℃로 냉각하고 진공 농축하여 용매를 제거하고 10% HCl 수용액으로 pH를 5~6로 맞추고 30분간 교반한다. MC 200ml를 투입하여 추출한다. 추출한 유기층은 MgSO4 처리하여 표제 화합물 17.0g을 수득하였다. (수율: 89.0%)tetraethyl 4,4',4'',4'''-(((ethane-1,2-diylbis((4-(ethoxycarbonyl)phenyl)azanediyl)) bis(ethane-2,1-diyl))bis( azanetriyl)) tetrabenzoate 22.9g, NaOH 6.1g, MeOH 180ml, purified water 140ml was added and the mixture was heated to 55-60°C and stirred for 12 hours to terminate the reaction. After cooling to 40°C and concentrating in vacuo to remove the solvent, adjust the pH to 5-6 with 10% aqueous HCl and stir for 30 minutes. MC 200ml is added to extract. The extracted organic layer was treated with MgSO 4 to obtain 17.0 g of the title compound. (Yield: 89.0%)
1H NMR (DMSO): 7.80(m, 4H), 7.68(m, 8H), 7.15(m, 8H), 6.94(m, 4H), 3.41~3.28(m, 12H) 1 H NMR (DMSO): 7.80 (m, 4H), 7.68 (m, 8H), 7.15 (m, 8H), 6.94 (m, 4H), 3.41-3.28 (m, 12H)
실시예Example 3: 5,5'-((2-((5-carboxypyridin-3-yl)(2-((5-carboxypyridin-3-yl)(2-((5-carboxypyridin-3-yl)(2-carboxypyridin-4-yl)amino)ethyl)amino)ethyl)amino)ethyl)azanediyl)dinicotinic acid (화학식 1g)의 제조 3: 5,5'-((2-((5-carboxypyridin-3-yl)(2-((5-carboxypyridin-3-yl)(2-((5-carboxypyridin-3-yl))(2- Preparation of carboxypyridin-4-yl)amino)ethyl)amino)ethyl)amino)ethyl)azanediyl)dinicotinic acid (Formula 1g)
Figure PCTKR2018016802-appb-I000033
Figure PCTKR2018016802-appb-I000033
Triethylenetetramine 10.0g, ethyl 5-bromonicotinate 108,5g, t-BuONa 46.0g과 Xylene 600ml를 투입 교반한다. 35℃로 승온하여 50% (t-Bu)3P toluene solution 2.8g을 투입하고 30분간 교반하고 50℃로 승온한 후 Pd(dba)2 2.0g을 투입하고 승온하여 환류교반하여 반응을 종결한다. 상온으로 냉각하여 정제수 1000ml를 투입하고 30분간 교반 정치하여 층분리하여 수층은 폐기한다. 유기층은 MgSO4 처리하여 진공 농축 후 MC-MeOH 컬럼 정제하여 diethyl 5,5'-((2-((5-(ethoxycarbonyl)pyridin-3-yl)(2-((5-(ethoxycarbonyl)pyridin-3-yl)(2-((5-(ethoxycarbonyl)pyridin-3-yl)(2-(ethoxycarbonyl)pyridin-4-yl)amino)ethyl)amino)ethyl)amino)ethyl)azanediyl)dinicotinate 19.8g을 수득 하였다. (수율: 27.8%)Triethylenetetramine 10.0g, ethyl 5-bromonicotinate 108,5g, t-BuONa 46.0g and Xylene 600ml are added and stirred. After heating up to 35°C, 2.8g of 50% (t-Bu) 3 P toluene solution was added, stirred for 30 minutes, heated to 50°C, and then 2.0g of Pd(dba)2 was added and heated to reflux stirring to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer. The organic layer was treated with MgSO 4, concentrated in vacuo, and purified by MC-MeOH column to diethyl 5,5'-((2-((5-(ethoxycarbonyl)pyridin-3-yl)(2-((5-(ethoxycarbonyl)pyridin- 3-yl)(2-((5-(ethoxycarbonyl)pyridin-3-yl)(2-(ethoxycarbonyl)pyridin-4-yl)amino)ethyl)amino)ethyl)amino)ethyl)azanediyl)dinicotinate 19.8g Was obtained. (Yield 27.8%)
1H NMR (CDCl3): 8.92(d, 4H), 8.85(d, 2H), 8.45(d, 4H), 8.43(d, 2H), 7.89(d, 4H), 7.76(d, 2H), 4.23(q, 8H), 4.15(q, 4H), 3.42~3.11(m, 12H), 1.27(t, 12H), 1.26(t, 6H) 1 H NMR (CDCl 3 ): 8.92(d, 4H), 8.85(d, 2H), 8.45(d, 4H), 8.43(d, 2H), 7.89(d, 4H), 7.76(d, 2H), 4.23(q, 8H), 4.15(q, 4H), 3.42~3.11(m, 12H), 1.27(t, 12H), 1.26(t, 6H)
diethyl 5,5'-((2-((5-(ethoxycarbonyl)pyridin-3-yl)(2-((5-(ethoxycarbonyl)pyridin 3-yl)(2-((5-(ethoxycarbonyl)pyridin-3-yl)(2-(ethoxycarbonyl)pyridin-4-yl)amino)ethyl)amino)ethyl)amino)ethyl)azanediyl)dinicotinate 19.8g과 NaOH 5.3g, MeOH 160ml, 정제수 120ml를 투입하고 55~60℃로 승온하여 12시간 교반하여 반응을 종결한다. 40℃로 냉각하고 진공 농축하여 용매를 제거하고 10% HCl 수용액으로 pH를 5~6로 맞추고 30분간 교반한다. MC 160ml를 투입하여 추출한다. 추출한 유기층은 MgSO4 처리하여 표제 화합물 13.0g을 수득하였다. (수율: 78.4%)diethyl 5,5'-((2-((5-(ethoxycarbonyl)pyridin-3-yl)(2-((5-(ethoxycarbonyl)pyridin 3-yl)(2-((5-(ethoxycarbonyl)pyridin- 3-yl)(2-(ethoxycarbonyl)pyridin-4-yl)amino)ethyl)amino)ethyl)amino)ethyl)azanediyl)dinicotinate 19.8g, NaOH 5.3g, MeOH 160ml, purified water 120ml was added and 55~60℃ The mixture was heated up and stirred for 12 hours to terminate the reaction. After cooling to 40°C and concentrating in vacuo to remove the solvent, adjust the pH to 5-6 with 10% aqueous HCl and stir for 30 minutes. MC 160ml is added to extract. The extracted organic layer was treated with MgSO 4 to obtain 13.0 g of the title compound. (Yield 78.4%)
1H NMR (DMSO): 8.95(d, 4H), 8.87(d, 2H), 8.46(d, 4H), 8.44(d, 2H), 7.89(d, 4H), 7.75(d, 2H), 3.41~3.11(m, 12H) 1 H NMR (DMSO): 8.95 (d, 4H), 8.87 (d, 2H), 8.46 (d, 4H), 8.44 (d, 2H), 7.89 (d, 4H), 7.75 (d, 2H), 3.41 ~3.11 (m, 12H)
실시예Example 4: 5,5',5'',5'''-(((ethane-1,2-diylbis((5-carboxyfuran-2-yl)azanediyl))bis(ethane-2,1-diyl))bis(azanetriyl))tetrakis(furan-2-carboxylic acid) (화학식 1h)의 제조 4: 5,5',5'',5'''-(((ethane-1,2-diylbis((5-carboxyfuran-2-yl)azanediyl))bis(ethane-2,1-diyl)) Preparation of bis(azanetriyl))tetrakis(furan-2-carboxylic acid) (Formula 1h)
Figure PCTKR2018016802-appb-I000034
Figure PCTKR2018016802-appb-I000034
Triethylenetetramine 10.0g, ethyl 5-bromofuran-2-carboxylate 103,3g, t-BuONa 46.0g과 toluene 600ml를 투입 교반한다. 35℃로 승온하여 50% (t-Bu)3P toluene solution 2.8g을 투입하고 30분간 교반하고 50℃로 승온한 후 Pd(dba)2 2.0g을 투입하고 승온하여 환류교반하여 반응을 종결한다. 상온으로 냉각하여 정제수 1000ml를 투입하고 30분간 교반 정치하여 층분리하여 수층은 폐기한다. 유기층은 MgSO4 처리하여 진공 농축 후 MC-MeOH 컬럼 정제하여 tetraethyl 5,5',5'',5'''-(((ethane-1,2-diylbis((5-(ethoxycarbonyl)furan-2-yl)azanediyl))bis(ethane-2,1-diyl))bis(azanetriyl))tetrakis(furan-2-carboxylate) 25.3g을 수득 하였다. (수율: 37.9%)Triethylenetetramine 10.0g, ethyl 5-bromofuran-2-carboxylate 103,3g, t-BuONa 46.0g and toluene 600ml were added and stirred. After heating up to 35°C, 2.8g of 50% (t-Bu) 3 P toluene solution was added, stirred for 30 minutes, heated to 50°C, and then 2.0g of Pd(dba)2 was added and heated to reflux stirring to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer. The organic layer was treated with MgSO 4, concentrated in vacuo, and purified by MC-MeOH column to tetraethyl 5,5',5'',5'''-(((ethane-1,2-diylbis((5-(ethoxycarbonyl)furan-2 25.3 g of -yl)azanediyl))bis(ethane-2,1-diyl))bis(azanetriyl))tetrakis(furan-2-carboxylate) was obtained. (Yield 37.9%)
1H NMR (CDCl3): 7.42(m, 12H), 4.31(q, 8H), 4.28(q, 4H), 3.65~3.15(m, 12H), 1.27(t, 12H), 1.25(t, 6H) 1 H NMR (CDCl 3 ): 7.42 (m, 12H), 4.31 (q, 8H), 4.28 (q, 4H), 3.65-3.15 (m, 12H), 1.27 (t, 12H), 1.25 (t, 6H) )
tetraethyl 5,5',5'',5'''-(((ethane-1,2-diylbis((5-(ethoxycarbonyl)furan-2-yl)azanediyl))bis (ethane-2,1-diyl))bis(azanetriyl))tetrakis(furan-2-carboxylate) 25.3g과 NaOH 7.2g, MeOH 200ml, 정제수 150ml를 투입하고 55~60℃로 승온하여 12시간 교반하여 반응을 종결한다. 40℃로 냉각하고 진공 농축하여 용매를 제거하고 10% HCl 수용액으로 pH를 5~6로 맞추고 30분간 교반한다. MC 200ml를 투입하여 추출한다. 추출한 유기층은 MgSO4 처리하여 표제 화합물 15.0g을 수득하였다. (수율: 71.8%)tetraethyl 5,5',5'',5'''-(((ethane-1,2-diylbis((5-(ethoxycarbonyl)furan-2-yl)azanediyl))bis (ethane-2,1-diyl ))bis(azanetriyl))tetrakis(furan-2-carboxylate) 25.3g, NaOH 7.2g, MeOH 200ml, 150ml of purified water was added and heated to 55~60℃ and stirred for 12 hours to terminate the reaction. After cooling to 40°C and concentrating in vacuo to remove the solvent, adjust the pH to 5-6 with 10% aqueous HCl and stir for 30 minutes. MC 200ml is added to extract. The extracted organic layer was treated with MgSO 4 to obtain 15.0 g of the title compound. (Yield: 71.8%)
1H NMR (DMSO): 7.41(m, 12H), 3.67~3.15(m, 12H) 1 H NMR (DMSO): 7.41 (m, 12H), 3.67-3.15 (m, 12H)
<사이클렌 유도체의 합성><Synthesis of cycline derivatives>
실시예Example 5: 25: 2 ,2',2'',2'''-(1,4,7,10-,2',2'',2'''-(1,4,7,10- tetraazacyclododecanetetraazacyclododecane -1,4,7,10-tetrayl)tetraacetic acid (화학식 2e)의 제조Preparation of -1,4,7,10-tetrayl)tetraacetic acid (Formula 2e)
Figure PCTKR2018016802-appb-I000035
Figure PCTKR2018016802-appb-I000035
Cyclen 10.0g과 acetonitrile 400.0ml를 투입 교반하고 K2CO3 40.1g과 Ethyl bromoacetate 42.7g을 투입하고 승온하여 40시간 환류교반하여 반응을 종결한다. 상온으로 냉각하여 여과하여 고체는 폐기하고 여액은 진공 농축한다. 농축액에 MC 200ml, 정제수 300ml 투입후 30분간 교반후 정치하여 층분리한다. 유기층은 MgSO4 처리하여 진공 농축 후 MC-MeOH로 컬럼정제하여 tetraethyl 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetate 15.7g을 수득하였다.(수율: 52.3%)Cyclen 10.0g and acetonitrile 400.0ml were added and stirred. 40.1g of K 2 CO 3 and 42.7g of Ethyl bromoacetate were added and heated to reflux stirring for 40 hours to terminate the reaction. Cool to room temperature, filter, discard the solid, and concentrate the filtrate in vacuo. After adding 200 ml of MC and 300 ml of purified water to the concentrate, the mixture was stirred for 30 minutes and left to separate. The organic layer was treated with MgSO 4 and concentrated in vacuo, and then purified by MC-MeOH to tetraethyl 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10- tetrayl)tetraacetate 15.7g was obtained. (Yield: 52.3%)
1H NMR (CDCl3): 4.19(q, 8H), 3.19(s, 8H), 2.48(s, 16H), 1.27(t, 12H) 1 H NMR (CDCl 3 ): 4.19 (q, 8H), 3.19 (s, 8H), 2.48 (s, 16H), 1.27 (t, 12H)
tetraethyl 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetate 15.7g과 NaOH 5.6g, MeOH 95ml, 정제수 60ml를 투입하고 55~60℃로 승온하여 12시간 교반하여 반응을 종결한다. 40℃로 냉각하고 진공 농축하여 용매를 제거하고 10% HCl 수용액으로 pH를 5~6로 맞추고 30분간 교반한다. MC 200ml를 투입하여 추출한다. 추출한 유기층은 MgSO4 처리하여 표제 화합물 9.9g을 수득하였다. (수율: 80.5%)tetraethyl 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetate 15.7g, NaOH 5.6g, MeOH 95ml, purified water 60ml The mixture was heated to 55-60° C. and stirred for 12 hours to terminate the reaction. After cooling to 40°C and concentrating in vacuo to remove the solvent, adjust the pH to 5-6 with 10% aqueous HCl and stir for 30 minutes. MC 200ml is added to extract. The extracted organic layer was treated with MgSO 4 to obtain 9.9 g of the title compound. (Yield: 80.5%)
1H NMR (DMSO): 3.88(s, 8H), 3.23(s, 16H) 1 H NMR (DMSO): 3.88 (s, 8H), 3.23 (s, 16H)
실시예Example 6: 46: 4 ,4',4'',4'''-(1,4,7,10-,4',4'',4'''-(1,4,7,10- tetraazacyclododecanetetraazacyclododecane -1,4,7,10-tetrayl)tetrabenzoic acid (화학식 2f)의 제조Preparation of -1,4,7,10-tetrayl)tetrabenzoic acid (Formula 2f)
Figure PCTKR2018016802-appb-I000036
Figure PCTKR2018016802-appb-I000036
Cyclen 10.0g, ethyl 4-bromobenzoate 58.5g, t-BuONa 27.9g과 toluene 400ml를 투입 교반한다. 35℃로 승온하여 50% (t-Bu)3P toluene solution 2.4g을 투입하고 30분간 교반하고 50℃로 승온한 후 Pd(dba)2 1.7g을 투입하고 승온하여 환류교반하여 반응을 종결한다. 상온으로 냉각하여 정제수 1000ml를 투입하고 30분간 교반 정치하여 층분리하여 수층은 폐기한다. 유기층은 MgSO4 처리하여 진공 농축 후 MC-MeOH 컬럼 정제하여 tetraethyl 4,4',4'',4'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrabenzoate 15.8g을 수득 하였다. (수율: 35.6%)Cyclen 10.0g, ethyl 4-bromobenzoate 58.5g, t-BuONa 27.9g and toluene 400ml were added and stirred. After heating to 35℃, 2.4g of 50% (t-Bu) 3 P toluene solution was added, stirred for 30 minutes, heated to 50℃, and 1.7g of Pd(dba)2 was added and heated to reflux stirring to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer. The organic layer was treated with MgSO 4, concentrated in vacuo, and purified by MC-MeOH column to tetraethyl 4,4',4'',4'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl )tetrabenzoate 15.8g was obtained. (Yield 35.6%)
1H NMR (CDCl3): 7.81(d, 8H), 6.98(d, 8H), 4,15(q, 8H), 3.48(s, 16H), 1,25(t, 12H) 1 H NMR (CDCl 3 ): 7.81 (d, 8H), 6.98 (d, 8H), 4,15 (q, 8H), 3.48 (s, 16H), 1,25 (t, 12H)
tetraethyl 4,4',4'',4'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrabenzoate 15.8g과 NaOH 3.8g, MeOH 130ml, 정제수 100ml를 투입하고 55~60℃로 승온하여 12시간 교반하여 반응을 종결한다. 40℃로 냉각하고 진공 농축하여 용매를 제거하고 10% HCl 수용액으로 pH를 5~6로 맞추고 30분간 교반한다. MC 130ml를 투입하여 추출한다. 추출한 유기층은 MgSO4 처리하여 표제 화합물 11.5g을 수득하였다. (수율: 85.2%)tetraethyl 4,4',4'',4'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrabenzoate 15.8g, NaOH 3.8g, MeOH 130ml, purified water 100ml The mixture was heated to 55-60° C. and stirred for 12 hours to terminate the reaction. After cooling to 40°C and concentrating in vacuo to remove the solvent, adjust the pH to 5-6 with 10% aqueous HCl and stir for 30 minutes. MC 130ml is added to extract. The extracted organic layer was treated with MgSO 4 to obtain 11.5 g of the title compound. (Yield 85.2%)
1H NMR (DMSO): 7.82(d, 8H), 6.97(d, 8H), 3.45(s, 16H) 1 H NMR (DMSO): 7.82 (d, 8H), 6.97 (d, 8H), 3.45 (s, 16H)
실시예Example 7: 57: 5 ,5',5'',5'''-(1,4,7,10-,5',5'',5'''-(1,4,7,10- tetraazacyclododecanetetraazacyclododecane -1,4,7,10-tetrayl)tetranicotinic acid (화학식 2g)의 제조Preparation of -1,4,7,10-tetrayl)tetranicotinic acid (Formula 2g)
Figure PCTKR2018016802-appb-I000037
Figure PCTKR2018016802-appb-I000037
Cyclen 10.0g, ethyl 5-bromonicotinate 58.7g, t-BuONa 27.9g과 xylene 400ml를 투입 교반한다. 35℃로 승온하여 50% (t-Bu)3P toluene solution 2.4g을 투입하고 30분간 교반하고 50℃로 승온한 후 Pd(dba)2 1.7g을 투입하고 승온하여 환류교반하여 반응을 종결한다. 상온으로 냉각하여 정제수 1000ml를 투입하고 30분간 교반 정치하여 층분리하여 수층은 폐기한다. 유기층은 MgSO4 처리하여 진공 농축 후 MC-MeOH 컬럼 정제하여 tetraethyl 5,5',5'',5'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetranicotinate 17.9g을 수득 하였다. (수율: 40.1%)Cyclen 10.0g, ethyl 5-bromonicotinate 58.7g, t-BuONa 27.9g and xylene 400ml were added and stirred. After heating to 35℃, 2.4g of 50% (t-Bu) 3 P toluene solution was added, stirred for 30 minutes, heated to 50℃, and 1.7g of Pd(dba)2 was added and heated to reflux stirring to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer. The organic layer was treated with MgSO 4, concentrated in vacuo, and purified by MC-MeOH column to tetraethyl 5,5',5'',5'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl )tetranicotinate 17.9g was obtained. (Yield 40.1%)
1H NMR (CDCl3): 8.95(d, 4H), 8.46(d, 4H), 7.83(d, 4H), 4,21(q, 8H), 3.38(s, 16H), 1,24(t, 12H) 1 H NMR (CDCl 3 ): 8.95(d, 4H), 8.46(d, 4H), 7.83(d, 4H), 4,21(q, 8H), 3.38(s, 16H), 1,24(t , 12H)
*tetraethyl 5,5',5'',5'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetranicotinate 17.9g과 NaOH 4.3g, MeOH 150ml, 정제수 110ml를 투입하고 55~60℃로 승온하여 12시간 교반하여 반응을 종결한다. 40℃로 냉각하고 진공 농축하여 용매를 제거하고 10% HCl 수용액으로 pH를 5~6로 맞추고 30분간 교반한다. MC 160ml를 투입하여 추출한다. 추출한 유기층은 MgSO4 처리하여 표제 화합물 11.6g을 수득하였다. (수율: 75.6%)*tetraethyl 5,5',5'',5'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetranicotinate 17.9g and NaOH 4.3g, MeOH 150ml, purified water 110ml Was added, the temperature was raised to 55-60° C., and the reaction was terminated by stirring for 12 hours. After cooling to 40°C and concentrating in vacuo to remove the solvent, adjust the pH to 5-6 with 10% aqueous HCl and stir for 30 minutes. MC 160ml is added to extract. The extracted organic layer was treated with MgSO 4 to obtain 11.6 g of the title compound. (Yield 75.6%)
1H NMR (DMSO): 8.96(d, 4H), 8.44(d, 4H), 7.84(d, 4H), 3.36(s, 16H) 1 H NMR (DMSO): 8.96 (d, 4H), 8.44 (d, 4H), 7.84 (d, 4H), 3.36 (s, 16H)
실시예Example 8: 58: 5 ,5',5'',5'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrakis(furan-2-carboxylic acid) (화학식 2h)의 제조Preparation of ,5',5'',5'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrakis(furan-2-carboxylic acid) (Formula 2h)
Figure PCTKR2018016802-appb-I000038
Figure PCTKR2018016802-appb-I000038
Cyclen 10.0g, ethyl 5-bromofuran-2-carboxylate 56.0g, t-BuONa 27.9g과 toluene 400ml를 투입 교반한다. 35℃로 승온하여 50% (t-Bu)3P toluene solution 2.4g을 투입하고 30분간 교반하고 50℃로 승온한 후 Pd(dba)2 1.7g을 투입하고 승온하여 환류교반하여 반응을 종결한다. 상온으로 냉각하여 정제수 1000ml를 투입하고 30분간 교반 정치하여 층분리하여 수층은 폐기한다. 유기층은 MgSO4 처리하여 진공 농축 후 MC-MeOH 컬럼 정제하여 tetraethyl 5,5',5'',5'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrakis(furan-2-carboxylate) 12.6g을 수득 하였다. (수율: 30.0%)Cyclen 10.0g, ethyl 5-bromofuran-2-carboxylate 56.0g, t-BuONa 27.9g and toluene 400ml were added and stirred. After heating to 35℃, 2.4g of 50% (t-Bu) 3 P toluene solution was added, stirred for 30 minutes, heated to 50℃, and 1.7g of Pd(dba)2 was added and heated to reflux stirring to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer. The organic layer was treated with MgSO 4, concentrated in vacuo, and purified by MC-MeOH column to tetraethyl 5,5',5'',5'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl )tetrakis (furan-2-carboxylate) 12.6g was obtained. (Yield: 30.0%)
1H NMR (CDCl3): 7.39(d, 8H), 4,35(q, 8H), 3.28(s, 16H), 1,35(t, 12H) 1 H NMR (CDCl 3 ): 7.39 (d, 8H), 4,35 (q, 8H), 3.28 (s, 16H), 1,35 (t, 12H)
tetraethyl 5,5',5'',5'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrakis(furan-2-carboxylate) 12.6g과 NaOH 3.2g, MeOH 100ml, 정제수 75ml를 투입하고 55~60℃로 승온하여 12시간 교반하여 반응을 종결한다. 40℃로 냉각하고 진공 농축하여 용매를 제거하고 10% HCl 수용액으로 pH를 5~6로 맞추고 30분간 교반한다. MC 100ml를 투입하여 추출한다. 추출한 유기층은 MgSO4 처리하여 표제 화합물 7.9g을 수득하였다. (수율: 73.9%)tetraethyl 5,5',5'',5'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrakis (furan-2-carboxylate) 12.6g and NaOH 3.2g , 100 ml of MeOH and 75 ml of purified water were added, and the mixture was heated to 55-60° C. and stirred for 12 hours to terminate the reaction. After cooling to 40°C and concentrating in vacuo to remove the solvent, adjust the pH to 5-6 with 10% aqueous HCl and stir for 30 minutes. MC 100ml is added to extract. The extracted organic layer was treated with MgSO 4 to obtain 7.9 g of the title compound. (Yield 73.9%)
1H NMR (DMSO): 7.40(d, 8H), 3.29(s, 16H) 1 H NMR (DMSO): 7.40 (d, 8H), 3.29 (s, 16H)
<사이클람 유도체의 합성><Synthesis of cyclam derivatives>
실시예Example 9: 29: 2 ,2',2'',2'''-(1,4,8,11-,2',2'',2'''-(1,4,8,11- tetraazacyclotetradecanetetraazacyclotetradecane -1,4,8,11-tetrayl)tetraacetic acid (화학식 3e)의 제조Preparation of -1,4,8,11-tetrayl)tetraacetic acid (Formula 3e)
Figure PCTKR2018016802-appb-I000039
Figure PCTKR2018016802-appb-I000039
Cyclam 10.0g과 acetonitrile 400.0ml를 투입 교반하고 K2CO3 34.5g과 Ethyl bromoacetate 36.7g을 투입하고 승온하여 40시간 환류교반하여 반응을 종결한다. 상온으로 냉각하여 여과하여 고체는 폐기하고 여액은 진공 농축한다. 농축액에 MC 200ml, 정제수 300ml 투입후 30분간 교반후 정치하여 층분리한다. 유기층은 MgSO4 처리하여 진공 농축 후 MC-MeOH로 컬럼정제하여 tetraethyl 2,2',2'',2'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetraacetate 15.4g을 수득하였다. (수율: 56.8%)10.0 g of Cyclam and 400.0 ml of acetonitrile were added and stirred, 34.5 g of K 2 CO 3 and 36.7 g of Ethyl bromoacetate were added, heated to reflux and stirred for 40 hours to terminate the reaction. Cool to room temperature, filter, discard the solid, and concentrate the filtrate in vacuo. After adding 200 ml of MC and 300 ml of purified water to the concentrate, the mixture was stirred for 30 minutes and left to separate. The organic layer was treated with MgSO 4, concentrated in vacuo, and purified by column with MC-MeOH to tetraethyl 2,2',2'',2'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11- Tetrayl)tetraacetate 15.4g was obtained. (Yield 56.8%)
1H NMR (CDCl3): 4.12(q, 8H), 3.36(s, 8H), 2,69~2.73(m, 16H), 1,60(m, 4H), 1.26(t, 12H) 1 H NMR (CDCl 3 ): 4.12(q, 8H), 3.36(s, 8H), 2,69~2.73(m, 16H), 1,60(m, 4H), 1.26(t, 12H)
*tetraethyl 2,2',2'',2'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetraacetate 15.4g과 NaOH 5.2g, MeOH 90ml, 정제수 60ml를 투입하고 55~60℃로 승온하여 12시간 교반하여 반응을 종결한다. 40℃로 냉각하고 진공 농축하여 용매를 제거하고 10% HCl 수용액으로 pH를 5~6로 맞추고 30분간 교반한다. MC 200ml를 투입하여 추출한다. 추출한 유기층은 MgSO4 처리하여 표제 화합물 9.3g을 수득하였다. (수율: 75.9%)*tetraethyl 2,2',2'',2'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetraacetate 15.4g and NaOH 5.2g, MeOH 90ml, purified water 60ml Was added, the temperature was raised to 55-60° C., and the reaction was terminated by stirring for 12 hours. After cooling to 40°C and concentrating in vacuo to remove the solvent, adjust the pH to 5-6 with 10% aqueous HCl and stir for 30 minutes. MC 200ml is added to extract. The extracted organic layer was treated with MgSO 4 to obtain 9.3 g of the title compound. (Yield: 75.9%)
1H NMR (D2O): 3.51(s, 8H), 3.14(s, 8H), 3.07(t, 8H), 1.85(q, 4H) 1 H NMR (D 2 O): 3.51 (s, 8H), 3.14 (s, 8H), 3.07 (t, 8H), 1.85 (q, 4H)
실시예Example 10: 410: 4 ,4',4'',4'''-(1,4,8,11-,4',4'',4'''-(1,4,8,11- tetraazacyclotetradecanetetraazacyclotetradecane -1,4,8,11-tetrayl)tetrabenzoic acid (화학식 3f)의 제조Preparation of -1,4,8,11-tetrayl)tetrabenzoic acid (Formula 3f)
Figure PCTKR2018016802-appb-I000040
Figure PCTKR2018016802-appb-I000040
Cyclam 10.0g, ethyl 4-bromobenzoate 50.3g, t-BuONa 24.0g과 toluene 400ml를 투입 교반한다. 35℃로 승온하여 50% (t-Bu)3P toluene solution 2.0g을 투입하고 30분간 교반하고 50℃로 승온한 후 Pd(dba)2 1.5g을 투입하고 승온하여 환류교반하여 반응을 종결한다. 상온으로 냉각하여 정제수 1000ml를 투입하고 30분간 교반 정치하여 층분리하여 수층은 폐기한다. 유기층은 MgSO4 처리하여 진공 농축 후 MC-MeOH 컬럼 정제하여 tetraethyl 4,4',4'',4'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetrabenzoate 12.3g을 수득 하였다. (수율: 31.0%)Cyclam 10.0g, ethyl 4-bromobenzoate 50.3g, t-BuONa 24.0g and toluene 400ml were added and stirred. After heating to 35°C, 2.0g of 50% (t-Bu) 3 P toluene solution was added, stirred for 30 minutes, heated to 50°C, and then 1.5g of Pd(dba)2 was added and heated to reflux stirring to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer. The organic layer is MgSO 4 After treatment, concentrated in vacuo and purified by MC-MeOH column, tetraethyl 4,4',4'',4'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetrabenzoate 12.3g Was obtained. (Yield 31.0%)
1H NMR (CDCl3): 7.80(d, 8H), 6.94(d, 8H),4.13(q, 8H), 2,65~2.71(m, 16H), 1,65(m, 4H), 1.26(t, 12H) 1 H NMR (CDCl 3 ): 7.80(d, 8H), 6.94(d, 8H),4.13(q, 8H), 2,65~2.71(m, 16H), 1,65(m, 4H), 1.26 (t, 12H)
tetraethyl 4,4',4'',4'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetrabenzoate 12.3g과 NaOH 2.6g, MeOH 100ml, 정제수 70ml를 투입하고 55~60℃로 승온하여 12시간 교반하여 반응을 종결한다. 40℃로 냉각하고 진공 농축하여 용매를 제거하고 10% HCl 수용액으로 pH를 5~6로 맞추고 30분간 교반한다. MC 100ml를 투입하여 추출한다. 추출한 유기층은 MgSO4 처리하여 표제 화합물 8.6g을 수득하였다. (수율: 81.2%)tetraethyl 4,4',4'',4'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetrabenzoate 12.3g, NaOH 2.6g, MeOH 100ml, purified water 70ml The mixture was heated to 55-60° C. and stirred for 12 hours to terminate the reaction. After cooling to 40°C and concentrating in vacuo to remove the solvent, adjust the pH to 5-6 with 10% aqueous HCl and stir for 30 minutes. MC 100ml is added to extract. The extracted organic layer was treated with MgSO 4 to obtain 8.6 g of the title compound. (Yield 81.2%)
1H NMR (DMSO): 7.83(d, 8H), 6.95(d, 8H), 2,63~2.73(m, 16H), 1,62(m, 4H) 1 H NMR (DMSO): 7.83 (d, 8H), 6.95 (d, 8H), 2,63-2.73 (m, 16H), 1,62 (m, 4H)
실시예Example 11: 511: 5 ,5',5'',5'''-(1,4,8,11-,5',5'',5'''-(1,4,8,11- tetraazacyclotetradecanetetraazacyclotetradecane -1,4,8,11-tetrayl)tetranicotinic acid (화학식 3g)의 제조Preparation of -1,4,8,11-tetrayl)tetranicotinic acid (Formula 3g)
Figure PCTKR2018016802-appb-I000041
Figure PCTKR2018016802-appb-I000041
Cyclam 10.0g, ethyl 5-bromonicotinate 50.3g, t-BuONa 24.0g과 xylene 400ml를 투입 교반한다. 35℃로 승온하여 50% (t-Bu)3P toluene solution 2.0g을 투입하고 30분간 교반하고 50℃로 승온한 후 Pd(dba)2 1.5g을 투입하고 승온하여 환류교반하여 반응을 종결한다. 상온으로 냉각하여 정제수 1000ml를 투입하고 30분간 교반 정치하여 층분리하여 수층은 폐기한다. 유기층은 MgSO4 처리하여 진공 농축 후 MC-MeOH 컬럼 정제하여 tetraethyl 5,5',5'',5'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetranicotinate 11.1g을 수득 하였다. (수율: 27.8%)Cyclam 10.0g, ethyl 5-bromonicotinate 50.3g, t-BuONa 24.0g and xylene 400ml were added and stirred. After heating up to 35°C, add 2.0g of 50% (t-Bu) 3 P toluene solution, stir for 30 minutes, heat up to 50°C, add 1.5g of Pd(dba)2, heat up, and stir to reflux to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer. The organic layer was treated with MgSO 4, concentrated in vacuo, and purified by MC-MeOH column to tetraethyl 5,5',5'',5'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl )tetranicotinate 11.1g was obtained. (Yield 27.8%)
1H NMR (CDCl3): 8.91(d, 4H), 8.37(d, 4H), 7.85(d, 4H), 4.15(q, 8H), 2,67~2.64(m, 16H), 1,71(m, 4H), 1.24(t, 12H) 1 H NMR (CDCl 3 ): 8.91(d, 4H), 8.37(d, 4H), 7.85(d, 4H), 4.15(q, 8H), 2,67~2.64(m, 16H), 1,71 (m, 4H), 1.24 (t, 12H)
tetraethyl 5,5',5'',5'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetranicotinate 11.1g과 NaOH 2.6g, MeOH 90ml, 정제수 70ml를 투입하고 55~60℃로 승온하여 12시간 교반하여 반응을 종결한다. 40℃로 냉각하고 진공 농축하여 용매를 제거하고 10% HCl 수용액으로 pH를 5~6로 맞추고 30분간 교반한다. MC 120ml를 투입하여 추출한다. 추출한 유기층은 MgSO4 처리하여 표제 화합물 7.4g을 수득하였다. (수율: 77.6%)tetraethyl 5,5',5'',5'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetranicotinate 11.1g, NaOH 2.6g, MeOH 90ml, purified water 70ml The mixture was heated to 55-60° C. and stirred for 12 hours to terminate the reaction. After cooling to 40°C and concentrating in vacuo to remove the solvent, adjust the pH to 5-6 with 10% aqueous HCl and stir for 30 minutes. MC 120ml is added to extract. The extracted organic layer was treated with MgSO 4 to obtain 7.4 g of the title compound. (Yield 77.6%)
1H NMR (DMSO): 8.93(d, 4H), 8.38(d, 4H), 7.85(d, 4H), 2,67~2.66(m, 16H), 1,72(m, 4H) 1 H NMR (DMSO): 8.93 (d, 4H), 8.38 (d, 4H), 7.85 (d, 4H), 2,67-2.66 (m, 16H), 1,72 (m, 4H)
실시예Example 12: 512: 5 ,5',5'',5'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetrakis(furan-2-carboxylic acid) (화학식 3h)의 제조Preparation of ,5',5'',5'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetrakis (furan-2-carboxylic acid) (Formula 3h)
Figure PCTKR2018016802-appb-I000042
Figure PCTKR2018016802-appb-I000042
Cyclam 10.0g, ethyl 5-bromofuran-2-carboxylate 48.1g, t-BuONa 24.0g과 toluene 400ml를 투입 교반한다. 35℃로 승온하여 50% (t-Bu)3P toluene solution 2.0g을 투입하고 30분간 교반하고 50℃로 승온한 후 Pd(dba)2 1.5g을 투입하고 승온하여 환류교반하여 반응을 종결한다. 상온으로 냉각하여 정제수 1000ml를 투입하고 30분간 교반 정치하여 층분리하여 수층은 폐기한다. 유기층은 MgSO4 처리하여 진공 농축 후 MC-MeOH 컬럼 정제하여 tetraethyl 5,5',5'',5'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetrakis(furan-2-carboxylate) 14.1g을 수득 하였다. (수율: 37.5%)Cyclam 10.0g, ethyl 5-bromofuran-2-carboxylate 48.1g, t-BuONa 24.0g and toluene 400ml were added and stirred. After heating to 35°C, 2.0g of 50% (t-Bu) 3 P toluene solution was added, stirred for 30 minutes, heated to 50°C, and then 1.5g of Pd(dba)2 was added and heated to reflux stirring to terminate the reaction. . After cooling to room temperature, 1000 ml of purified water was added and the mixture was left to stir for 30 minutes to separate the layers and discard the aqueous layer. The organic layer was treated with MgSO 4 and concentrated in vacuo, followed by purification of an MC-MeOH column to tetraethyl 5,5',5'',5'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl )tetrakis (furan-2-carboxylate) 14.1g was obtained. (Yield 37.5%)
1H NMR (CDCl3): 7.40(d, 8H), 4.23(q, 8H), 2,65~2.71(m, 16H), 1,66(m, 4H), 1.29(t, 12H) 1 H NMR (CDCl 3 ): 7.40(d, 8H), 4.23(q, 8H), 2,65~2.71(m, 16H), 1,66(m, 4H), 1.29(t, 12H)
tetraethyl 5,5',5'',5'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetrakis(furan-2-carboxylate) 14.1g과 NaOH 3.5g, MeOH 110ml, 정제수 85ml를 투입하고 55~60℃로 승온하여 12시간 교반하여 반응을 종결한다. 40℃로 냉각하고 진공 농축하여 용매를 제거하고 10% HCl 수용액으로 pH를 5~6로 맞추고 30분간 교반한다. MC 120ml를 투입하여 추출한다. 추출한 유기층은 MgSO4 처리하여 표제 화합물 9.4g을 수득하였다.(수율: 78.1%)tetraethyl 5,5',5'',5'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetrakis (furan-2-carboxylate) 14.1g and NaOH 3.5g , 110 ml of MeOH and 85 ml of purified water were added and the mixture was heated to 55-60° C. and stirred for 12 hours to terminate the reaction. After cooling to 40°C and concentrating in vacuo to remove the solvent, the pH is adjusted to 5-6 with 10% aqueous HCl and stirred for 30 minutes. MC 120ml is added to extract. The extracted organic layer was treated with MgSO 4 to obtain 9.4 g of the title compound. (Yield: 78.1%)
1H NMR (DMSO): 7.41(d, 8H), 2,69~2.72(m, 16H), 1,68(m, 4H) 1 H NMR (DMSO): 7.41 (d, 8H), 2,69-2.72 (m, 16H), 1,68 (m, 4H)
실시예 13 내지 27: 공기 필터의 제조Examples 13 to 27: Preparation of air filter
트리엔틴, 사이클렌, 사이클람 및 상기 실시예 1 내지 12에서 제조된 트리엔틴 유도체, 사이클렌 유도체, 사이클람 유도체를 1% 수용액으로 제조한 다음, 시중에서 판매되는 공기 필터용 5T 부직포(PET 소재)를 구입하여 10 cm * 10 cm 로 절단한 후, 상기 수용액에 30초간 스프레이 분사시켜 충분히 적신 다음, 3시간 건조시켜 본 발명에 따른 유효성분이 함유된 필터를 제조하였다.Trientine, cyclene, cyclam, and the trientine derivatives, cyclene derivatives, and cyclam derivatives prepared in Examples 1 to 12 were prepared as a 1% aqueous solution, and then commercially available 5T nonwoven fabric for air filters ( PET material) was purchased, cut into 10 cm * 10 cm, sprayed with the aqueous solution for 30 seconds, sufficiently wetted, and then dried for 3 hours to prepare a filter containing the active ingredient according to the present invention.
공기 필터의 각 유효 성분들을 하기 표 1에 나타내었다.Each active component of the air filter is shown in Table 1 below.
공기 필터Air filter 유효성분Active ingredient
실시예 13Example 13 트리엔틴Trientine
실시예 14Example 14 실시예 1Example 1
실시예 15Example 15 실시예 2Example 2
실시예 16Example 16 실시예 3Example 3
실시예 17Example 17 실시예 4Example 4
실시예 18Example 18 사이클렌Cyclen
실시예 19Example 19 실시예 5Example 5
실시예 20Example 20 실시예 6Example 6
실시예 21Example 21 실시예 7Example 7
실시예 22Example 22 실시예 8Example 8
실시예 23Example 23 사이클람Cyclam
실시예 24Example 24 실시예 9Example 9
실시예 25Example 25 실시예 10Example 10
실시예 26Example 26 실시예 11Example 11
실시예 27Example 27 실시예 12Example 12
비교예 1Comparative Example 1 --
실험예 1: 공기 필터의 중금속 제거능 시험Experimental Example 1: Heavy metal removal ability test of air filter
상기 제조된 필터들은 폐쇄된 공간에 나란히 세워두고 외부에서 포집된 다량의 미세먼지를 투입한 후, 필터들에 미세먼지가 부착되도록 내부에 설치된 팬들을 1일 동안 가동시킨 다음, 오염된 필터들을 증류수(1L)에 넣어 혼합한 후, 총중금속 검사 키트(WAK-MeTM, 일본 Kyoritsu Chemical-Check Lab.)를 이용하여 미세먼지 수용액의 총중금속량(Cu, Zn, Mn, Ni,Cd)을 측정하였다.The manufactured filters are placed side by side in a closed space, and a large amount of fine dust collected from the outside is put in, and then the fans installed therein are operated for 1 day to attach the fine dust to the filters, and then the contaminated filters are distilled. After mixing in (1 L), the total heavy metal amount (Cu, Zn, Mn, Ni, Cd) of the fine dust aqueous solution was measured using a total heavy metal test kit (WAK-Me TM , Kyoritsu Chemical-Check Lab., Japan). Did.
총중금속량의 측정은 수용액의 발색을 표준 색상과 비교하여 그 결과를 표 2에 도시하였다.The measurement of the total heavy metal amount is shown in Table 2 by comparing the color development of the aqueous solution with the standard color.
(황색) 0 ppm 0.2 ppm 0.5 ppm 1.0 ppm 2.0 ppm ≤5 ppm (적색)(Yellow) 0 ppm 0.2 ppm 0.5 ppm 1.0 ppm 2.0 ppm ≤5 ppm (Red)
필터filter 유효성분Active ingredient 총중금속량(Cu, Zn, Mn, Ni, Cd) (ppm)Total Heavy Metals (Cu, Zn, Mn, Ni, Cd) (ppm)
실시예 13Example 13 트리엔틴Trientine ≤5 (적색)≤5 (red)
실시예 14Example 14 실시예 1Example 1 ≤5≤5
실시예 15Example 15 실시예 2Example 2 ≤5≤5
실시예 16Example 16 실시예 3Example 3 ≤5≤5
실시예 17Example 17 실시예 4Example 4 ≤5≤5
실시예 18Example 18 사이클렌Cyclen ≤5≤5
실시예 19Example 19 실시예 5Example 5 ≤5≤5
실시예 20Example 20 실시예 6Example 6 ≤5≤5
실시예 21Example 21 실시예 7Example 7 ≤5≤5
실시예 22Example 22 실시예 8Example 8 ≤5≤5
실시예 23Example 23 사이클람Cyclam ≤5≤5
실시예 24Example 24 실시예 9Example 9 ≤5≤5
실시예 25Example 25 실시예 10Example 10 ≤5≤5
실시예 26Example 26 실시예 11Example 11 ≤5≤5
실시예 27Example 27 실시예 12Example 12 ≤5≤5
비교예 1Comparative Example 1 -- 2.02.0
상기 표 2에 보이는 바와 같이 본 발명의 유효성분을 함유하지 않은 비교예 1의 필터에는 총중금속량은 2.0 ppm 이었으나, 본 발명에 따른 필터에 함유된 총중금속량은 모두 5 ppm 이상(≤5)으로 본 발명에 따른 필터들의 유해 중금속 흡착능이 현저한 것을 확인할 수 있다.As shown in Table 2, in the filter of Comparative Example 1, which did not contain the active ingredient of the present invention, the total heavy metal content was 2.0 ppm, but the total heavy metal content in the filter according to the present invention was all 5 ppm or more (≤5) It can be seen that the harmful heavy metal adsorption capacity of the filters according to the present invention is remarkable.
실험예 2: 유효성분의 피부 자극도 시험Experimental Example 2: Skin irritation test of active ingredient
20-30대 남녀 각각 10명, 총 20명을 대상으로 CTFA(The Cosmetic, Toiletry & Fragrance Association. Inc. Washington, D.C., 20036, 1991) 가이드라인에 따라 첩포의 방법으로 인체피부 1차 자극시험을 실시하였다.The first stimulation test for human skin was conducted by the method of patching according to the guidelines of CTFA (The Cosmetic, Toiletry & Fragrance Association.Inc. It was carried out.
먼저 8mm 직경, 10 패널 핀 챔버(Finn Chamber)에 쳄버용 필터페이퍼 디스크를 안치시키고 상기 실험예 1에 따른 외피용 조성물을 각각 20㎕씩 적하시키고, 10분간 자연 건조시킨 후, 등 부위에 Scanpor tape로 고정시켰다.First, place the filter paper disk for the chamber in an 8 mm diameter, 10 panel pin chamber, and drop 20 μl each of the composition for the outer sheath according to Experimental Example 1 above, naturally dry for 10 minutes, and then scanpor tape on the back area. Was fixed with.
24시간 경과 후 핀 챔버를 제거하고 육안으로 피부 변화를 관찰하여 하기 수학식 2에 따라 피부 자극도 및 판정 등급을 계산하여 하기 표 3에 그 결과를 나타내었다.After 24 hours, the pin chamber was removed and skin changes were visually observed to calculate skin irritation and determination grade according to Equation 2 below, and the results are shown in Table 3 below.
[수학식 1][Equation 1]
Figure PCTKR2018016802-appb-I000043
Figure PCTKR2018016802-appb-I000043
[피부 자극 판정 기준][Criteria for skin irritation determination]
(-): 홍반이나 특히 현상 없음; (±주위보다 약간 붉어짐; (+): 주위보다 현저히 붉어짐; (++): 주위보다 심하게 붉어지고 부풀어 오름. (-): No erythema or especially symptoms; (±Red slightly around the periphery; (+): Significantly reddened than the surroundings; (++): Reddened and swollen more severely than the surroundings.
[피부 자극 판정 등급][Skin irritation judgment grade]
자극도 0~0.1: 등급 Ⅰ(무자극 범위); 0.11~0.3: 등급 Ⅱ(경자극 범위); 0.31~0.5: 등급 Ⅲ(중자극 범위); 0.51이상: 등급 Ⅳ(강자극 범위)Stimulus 0~0.1: Grade I (no irritation range); 0.11 to 0.3: grade II (light stimulation range); 0.31 to 0.5: grade III (medium stimulation range); 0.51 or higher: Class IV (strong stimulation range)
시료sample 판정 결과(인원)Judgment result (person) 자극도Irritation 등급Rating
유효성분Active ingredient 함량(중량%)Content (% by weight) (-)(-) (±(± (+)(+) (++)(++)
트리엔틴Trientine 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 1919 1One 00 00 0.050.05 II
1.0%1.0% 1717 33 00 00 0.150.15 IIII
실시예 1Example 1 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 1919 1One 00 00 0.050.05 II
1.0%1.0% 1616 44 00 00 0.200.20 IIII
실시예 2Example 2 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 2020 00 00 00 00 II
1.0%1.0% 1919 1One 00 00 0.050.05 II
실시예 3Example 3 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 2020 00 00 00 00 II
1.0%1.0% 1919 1One 00 00 0.050.05 II
실시예 4Example 4 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 2020 00 00 00 00 II
1.0%1.0% 1919 1One 00 00 0.050.05 II
사이클렌Cyclen 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 2020 00 00 00 00 II
1.0%1.0% 1818 1One 1One 00 0.150.15 IIII
실시예 5Example 5 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 2020 00 00 00 00 II
1.0%1.0% 1919 1One 00 00 0.050.05 II
실시예 6Example 6 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 2020 00 00 00 00 II
1.0%1.0% 1919 1One 00 00 0.050.05 II
실시예 7Example 7 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 2020 00 00 00 00 II
1.0%1.0% 2020 00 00 00 00 II
실시예 8Example 8 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 2020 00 00 00 00 II
1.0%1.0% 1818 22 00 00 0.100.10 II
사이클람Cyclam 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 1919 1One 00 00 0.050.05 II
1.0%1.0% 1717 33 00 00 0.150.15 IIII
실시예 9Example 9 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 2020 00 00 00 00 II
1.0%1.0% 1818 22 00 00 0.100.10 II
실시예 10Example 10 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 2020 00 00 00 00 II
1.0%1.0% 1919 1One 00 00 0.050.05 II
실시예 11Example 11 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 2020 00 00 00 00 II
1.0%1.0% 1818 22 00 00 0.100.10 II
실시예 12Example 12 0.1%0.1% 2020 00 00 00 00 II
0.5%0.5% 2020 00 00 00 00 II
1.0%1.0% 1919 1One 00 00 0.050.05 II
비교예 1(EDTA)Comparative Example 1 (EDTA) 0.1%0.1% 2020 22 00 00 0.100.10 II
0.5%0.5% 1717 22 1One 00 0.200.20 IIII
1.0%1.0% 1515 33 22 00 0.350.35 IIIIII
상기 표 3에 나타나는 바와 같이, 본 발명의 실시예에 따른 중금속 킬레이트제 화합물은 인체 피부 자극 실험에서 0.5 중량% 농도 범위까지는 모두 무자극 범위인 등급 Ⅰ을 보였으며, 1.0 중량% 농도 범위에서는 트리엔틴, 사이클렌, 사이클람은 등급 Ⅱ(경자극 범위)를 보인 반면, 이들의 방향족, 복소환 유도체에서는 모두 등급 I을 보여 피부 자극 감소가 향상됨을 알 수 있다. 반면, 비교예 1의 EDTA는 1.0 중량% 농도에서 등급 Ⅲ(중자극 범위)으로 판정되어 본 발명의 화합물에 비해 피부 자극도가 높은 것을 알 수 있다. 따라서 본 발명에 따른 필터는 인체에 무해하여 담배 필터나 공기 마스크 등에 이용될 수 있음을 알 수 있다.As shown in Table 3, the heavy metal chelating agent compound according to the embodiment of the present invention showed a class I in the irritation range up to 0.5 wt% concentration range in the human skin irritation experiment, and triene in the 1.0 wt% concentration range While tin, cyclin, and cyclam showed grade II (light stimulation range), their aromatic and heterocyclic derivatives all showed grade I, suggesting that skin irritation reduction is improved. On the other hand, EDTA of Comparative Example 1 was determined to be grade III (medium irritation range) at a concentration of 1.0% by weight, indicating that the skin irritation was higher than that of the compound of the present invention. Therefore, it can be seen that the filter according to the present invention is harmless to the human body and can be used for a cigarette filter or an air mask.
실시예 28 내지 42: 담배 필터의 제조Examples 28-42: Preparation of cigarette filter
트리엔틴, 사이클렌, 사이클람 및 상기 실시예 1 내지 12에서 제조된 트리엔틴 유도체, 사이클렌 유도체, 사이클람 유도체를 각각 0.5%, 1.0%, 2.0% 수용액으로 제조한 후, 시중에서 판매되는 담배를 구입하여 담배 필터의 아랫 1/4부분을 상기 수용액에 4초간 함침시켜 본 발명의 유효성분이 필터에 적절히 스며들게 한 다음, 1시간 건조시켜 본 발명의 유효성분을 함유하는 담배 필터를 제조하였다.Trientine, cyclene, cyclam, and trientine derivatives, cycline derivatives, and cyclam derivatives prepared in Examples 1 to 12 were prepared as 0.5%, 1.0%, and 2.0% aqueous solutions, respectively, and sold commercially. A tobacco filter containing the active ingredient of the present invention was prepared by purchasing the tobacco to be impregnated with the aqueous solution in the lower quarter of the tobacco filter for 4 seconds, and then drying the active ingredient of the present invention for 1 hour. .
담배 필터의 유효성분을 하기 표 4에 나타내었다.Table 4 shows the active ingredients of the cigarette filter.
필터filter 유효성분Active ingredient
실시예 28Example 28 트리엔틴Trientine
실시예 29Example 29 실시예 1Example 1
실시예 30Example 30 실시예 2Example 2
실시예 31Example 31 실시예 3Example 3
실시예 32Example 32 실시예 4Example 4
실시예 33Example 33 사이클렌Cyclen
실시예 34Example 34 실시예 5Example 5
실시예 35Example 35 실시예 6Example 6
실시예 36Example 36 실시예 7Example 7
실시예 37Example 37 실시예 8Example 8
실시예 38Example 38 사이클람Cyclam
실시예 39Example 39 실시예 9Example 9
실시예 40Example 40 실시예 10Example 10
실시예 41Example 41 실시예 11Example 11
실시예 42Example 42 실시예 12Example 12
비교예 2Comparative Example 2 --
실험예 3: 담배 필터의 중금속 제거능Experimental Example 3: Heavy metal removal ability of cigarette filter
상기 실시예 2에서 제조된 유효성분을 함유하는 필터 담배들을 동일 유효성분 별 4개피을 1개조 샘플로 준비하고, 실제 흡연과 유사한 조건으로 설정된 흡입장치에 위치 고정한 후 불을 붙인후 흡입장치를 작동시켜 흡연을 실시하였다.Filter cigarettes containing the active ingredient prepared in Example 2 were prepared as a sample of 4 samples per active ingredient, placed in an inhalation device set to conditions similar to actual smoking, lighted, and then activated the inhalation device. Smoking was conducted.
상기 흡연된 담배 필터들을 수거하여 각 샘플(4개피 1개조) 각각 메탄올 100 ml에 넣어 60분간 초음파 진탕하여 추출하고, 상온에서 식힌 다음 메탄올을 넣어 100 ml로 한 다음, 필터를 빼낸 시료들을 30 ml 정도로 농축하여 검액을 준비하였다.The smoked cigarette filters were collected, and each sample (one set of 4 skins) was put into 100 ml of methanol, extracted by ultrasonic shaking for 60 minutes, cooled to room temperature, and then put into methanol to make 100 ml, and then 30 ml of samples with the filter removed It concentrated to the extent to prepare a test solution.
상기 준비된 검액을 유도결합플라즈마 질량분석기(ICP-MS, Inductively Coupled Plasma Mass Spectrometer)(XseriesTM 2, Thermo Fisher Scientific사, UK)를 이용하여 해당 중금속 성분을 분석하였다.The prepared sample was analyzed for the heavy metal component using an inductively coupled plasma mass spectrometer (ICP-MS, Inductively Coupled Plasma Mass Spectrometer) (Xseries TM 2, Thermo Fisher Scientific, UK).
ICP-MS에서 비소(As)의 측정질량(m/z)는 75, 카드뮴(Cd)은 114, 니켈(Ni) 60 위치의 수치를 측정하고, 하기 수학식 2와 같이 대조구 대비 중금속 흡착율을 계산하여 표 1에 나타내었다.In ICP-MS, the measured mass (m/z) of arsenic (As) is 75, cadmium (Cd) is 114, and the value of nickel (Ni) 60 is measured. It was shown in Table 1.
[수학식 2][Equation 2]
중금속 흡착율(%)=(실시예의 중금속 흡착량/대조구의 중금속 흡착량)×100Heavy metal adsorption rate (%) = (Example of heavy metal adsorption/control metal heavy adsorption) × 100
시료sample 비소(As)Arsenic (As) 카드뮴(Cd)Cadmium (Cd) 니켈(Ni)Nickel (Ni)
유효성분Active ingredient 함량content 흡착량(ppm)Adsorption (ppm) 흡착율(%)Adsorption rate (%) 흡착량(ppm)Adsorption (ppm) 흡착율(%)Adsorption rate (%) 흡착량(ppm)Adsorption (ppm) 흡착율(%)Adsorption rate (%)
트리엔틴Trientine 0.5%0.5% 4646 200%200% 7979 176%176% 102102 155%155%
1.0%1.0% 5353 230%230% 8484 187%187% 125125 189%189%
2.0%2.0% 6262 270%270% 9696 213%213% 131131 198%198%
실시예 1Example 1 0.5%0.5% 4343 187%187% 7777 171%171% 8989 135%135%
1.0%1.0% 4848 209%209% 7979 176%176% 101101 153%153%
2.0%2.0% 6363 274%274% 8484 187%187% 122122 185%185%
실시예 2Example 2 0.5%0.5% 4444 191%191% 7575 167%167% 9494 142%142%
1.0%1.0% 4848 209%209% 8484 187%187% 9898 148%148%
2.0%2.0% 5858 252%252% 9393 207%207% 103103 156%156%
실시예 3Example 3 0.5%0.5% 4848 209%209% 7575 167%167% 8989 135%135%
.0%.0% 5353 230%230% 8181 180%180% 102102 155%155%
.0%.0% 6363 274%274% 8686 191%191% 126126 191%191%
실시예 4Example 4 0.5%0.5% 4747 204%204% 6767 149%149% 9191 138%138%
1.0%1.0% 5656 243%243% 7575 167%167% 9898 148%148%
2.0%2.0% 6161 265%265% 8080 178%178% 104104 158%158%
사이클렌Cyclen 0.5%0.5% 3939 170%170% 6565 144%144% 8989 135%135%
1.0%1.0% 4343 187%187% 7878 173%173% 9393 141%141%
2.0%2.0% 5656 243%243% 8282 182%182% 9898 148%148%
실시예 5Example 5 0.5%0.5% 4141 178%178% 5959 131%131% 8383 126%126%
1.0%1.0% 4646 200%200% 6666 147%147% 8888 133%133%
2.0%2.0% 5151 222%222% 7070 156%156% 8989 135%135%
실시예 6Example 6 0.5%0.5% 4040 174%174% 6161 136%136% 7979 120%120%
1.0%1.0% 4141 178%178% 6868 151%151% 8383 126%126%
2.0%2.0% 4646 200%200% 7373 162%162% 8787 132%132%
실시예 7Example 7 0.5%0.5% 3939 170%170% 6464 142%142% 9292 139%139%
1.0%1.0% 4646 200%200% 7171 158%158% 9797 147%147%
2.0%2.0% 5555 239%239% 7878 173%173% 102102 155%155%
실시예 8Example 8 0.5%0.5% 3737 161%161% 5858 129%129% 8686 130%130%
1.0%1.0% 4848 209%209% 6161 136%136% 9191 138%138%
2.0%2.0% 4949 213%213% 7070 156%156% 9999 150%150%
사이클람Cyclam 0.5%0.5% 3737 161%161% 6060 133%133% 7979 120%120%
1.0%1.0% 4141 178%178% 7171 158%158% 8686 130%130%
2.0%2.0% 5656 243%243% 7878 173%173% 8989 135%135%
실시예 9Example 9 0.5%0.5% 4141 178%178% 6161 136%136% 7676 115%115%
1.0%1.0% 4646 200%200% 6363 140%140% 8585 129%129%
2.0%2.0% 4545 196%196% 7070 156%156% 9696 145%145%
실시예 10Example 10 0.5%0.5% 3636 157%157% 5858 129%129% 8181 123%123%
1.0%1.0% 3939 170%170% 6363 140%140% 8989 135%135%
2.0%2.0% 5151 222%222% 7171 158%158% 9494 142%142%
실시예 11Example 11 0.5%0.5% 3737 161%161% 5959 131%131% 7979 120%120%
1.0%1.0% 4545 196%196% 6363 140%140% 9090 136%136%
2.0%2.0% 5151 222%222% 7070 156%156% 8989 135%135%
실시예 12Example 12 0.5%0.5% 3434 148%148% 5858 129%129% 7777 117%117%
1.0%1.0% 3939 170%170% 6767 149%149% 8585 129%129%
2.0%2.0% 4343 187%187% 7272 160%160% 8989 135%135%
대조구 1Control 1 -- 2323 4545 6666
상기 표 5에 도시된 바와 같이 본 발명의 실시예에 따른 중금속 킬레이트제 화합물을 함유하는 담배 필터의 비소(Pb) 흡착율은 대조구와 대비할 때, 약 148~274%, 카드뮴(Cd) 흡착율은 129~213%, 니켈(Ni) 흡착율은 117~191%로, 유효성분의 함량이 증가할 수록 중금속 흡착율이 유의적으로 증가하는 것을 확인할 수 있다.이는 본 발명에 따른 유효성분을 함유하는 담배 필터가 유효성분 비함유 담배 필터에 비해 현저히 우수한 중금속 제거능을 가짐을 의미한다.As shown in Table 5, the adsorption rate of arsenic (Pb) of the cigarette filter containing the heavy metal chelating agent compound according to the embodiment of the present invention is about 148 to 274%, and the cadmium (Cd) adsorption rate is 129 to The adsorption rate of 213% and nickel (Ni) is 117 to 191%, and it can be seen that the heavy metal adsorption rate increases significantly as the content of the active ingredient increases. This is effective for the cigarette filter containing the active ingredient according to the present invention. It means that it has a remarkably superior ability to remove heavy metals compared to a non-component tobacco filter.
실험예 4: 포름알데히드 제거능 시험Experimental Example 4: Formaldehyde removal ability test
35.0% 포름알데히드 용액에 정제수를 넣고 2.0% 포름알데히드 희석액을 제조하였다. 상기 희석액에 3 mol 당량에 해당하는 본 발명의 트리엔틴, 사이클렌, 사이클람과 이들의 유도체 화합물을 각각 투입하고 상온에서 교반하면서 포름알데히드 변화량을 가스 크로마토그래피(GC) 분석을 실시하여 관찰하였다.Purified water was added to a 35.0% formaldehyde solution to prepare a 2.0% formaldehyde dilution. Trientine, cyclene, cyclam and their derivatives of the present invention corresponding to 3 mol equivalents were added to the diluent, respectively, and the amount of change in formaldehyde was observed by performing gas chromatography (GC) analysis while stirring at room temperature. .
포름알데히드의 함량은 하기 분석조건에서 실시되었으며, 초기, 30분, 180분 경과 후 포름알데히드의 함량을 표 6에 도시하였다.The content of formaldehyde was performed under the following analytical conditions, and the content of formaldehyde after initial, 30 minutes, and 180 minutes is shown in Table 6.
<GC 분석조건><GC analysis conditions>
- 검출기: 불꽃이온화검출기 -Detector: Flame ionization detector
- 칼럼: ZB-1 (0.32 mm × 30 m, 3.00 μm) 또는 이와 유사한 칼럼. Column: ZB-1 (0.32 mm×30 m, 3.00 μm) or similar column.
- 헤드스페이스조건: 평형온도 60 ℃, 평형시간 10 분, 이송라인온도 : 65℃ -Head space condition: Equilibrium temperature 60℃, Equilibration time 10 minutes, Transfer line temperature: 65℃
- 칼럼온도: 처음 5 분간 50 ℃로 유지하고, 그 다음 매 분 30 ℃씩 200 ℃까지 온도를 올리고 200 ℃에서 10 분간 유지. -Column temperature: maintained at 50 °C for the first 5 minutes, then raised to 200 °C by 30 °C every minute and held at 200 °C for 10 minutes.
- 검체도입부온도: 140 ℃ 부근의 일정 온도. -Sample introduction temperature: Constant temperature around 140 ℃.
- 검출기온도: 250 ℃ 부근의 일정 온도. -Detector temperature: Constant temperature around 250 ℃.
- 운반기체: 질소 -Carrier gas: Nitrogen
- 분할 비: 약 1:20 -Split ratio: about 1:20
- 유 량: 2.5 mL/분 -Flow rate: 2.5 mL/min
- 주입량: 검액 5uL를 마이크로 실린지로 바이알에 주입 밀전후 헤드스페이스조건에 따라 유지하고 증기상 1 mL를 칼럼에 주입. -Injection volume: 5uL of the sample solution is injected into a vial with a micro syringe, and kept in accordance with the headspace conditions before and after the flow, and 1 mL of the vapor phase is injected into the column.
- 분석시간 : 20 분 -Analysis time: 20 minutes
유효성분Active ingredient 면적(mAU*min)Area (mAU*min)
InitialInitial 30분30 minutes 180분180 minutes
트리엔틴Trientine 0.3050.305 0.1680.168 00
실시예 1Example 1 0.3050.305 0.1700.170 00
실시예 2Example 2 0.3050.305 0.1680.168 00
실시예 3Example 3 0.3050.305 0.1710.171 00
실시예 4Example 4 0.3050.305 0.1730.173 00
사이클렌Cyclen 0.3050.305 0.1810.181 00
실시예 5Example 5 0.3050.305 0.1790.179 00
실시예 6Example 6 0.3050.305 0.1830.183 00
실시예 7Example 7 0.3050.305 0.1810.181 00
실시예 8Example 8 0.3050.305 0.1680.168 00
사이클람Cyclam 0.3050.305 0.1720.172 00
실시예 9Example 9 0.3050.305 0.1820.182 00
실시예 10Example 10 0.3050.305 0.1710.171 00
실시예 11Example 11 0.3050.305 0.1740.174 00
실시예 12Example 12 0.3050.305 0.1700.170 00
상기 표 6에 보이는 바와 같이 GC 분석 결과, 본 발명의 화합물 투입 30분 만에 포름알데히드는 초기 대비 40~45% 정도 줄었으며, 180분 후에는 검출되지 않아 완전 사라짐을 확인하였다. 이는 본 발명의 유효성분이 포름알데히드와 효과적으로 흡착함을 의미하는 것으로, 본 발명에 따른 가구 세정용 조성물은 새집증후군의 원인 물질인 포름알데히드 제거에 유용하게 이용될 수 있음을 알 수 있다.As shown in Table 6, as a result of GC analysis, it was confirmed that formaldehyde was reduced by 40 to 45% compared to the initial 30 minutes after the compound was added to the present invention, and was completely undetected after 180 minutes. This means that the active ingredient of the present invention effectively adsorbs to formaldehyde, and it can be seen that the composition for cleaning furniture according to the present invention can be usefully used to remove formaldehyde, a causative agent of sick house syndrome.
본 발명은 중금속과 포름알데히드를 효과적으로 제거하기 위한 필터에 관한 것으로, 보다 상세히는 가정용·자동차용 공기청정기, 에어컨 등의 다양한 공조시스템에 이용될 수 있는 공기 필터, 담배 필터, 공기마스크에 관한 것이다.The present invention relates to a filter for effectively removing heavy metals and formaldehyde, and more particularly, to an air filter, a cigarette filter, and an air mask that can be used in various air conditioning systems such as household and automobile air purifiers and air conditioners.

Claims (13)

  1. 하기 화학식 1로 표시되는 트리엔틴 또는 트리엔틴 유도체, 하기 화학식 2로 표시되는 사이클렌 또는 사이클렌 유도체, 하기 화학식 3으로 표시되는 사이클람 또는 사이클람 유도체 중에서 선택된 1종 이상을 유효성분으로 하는, 중금속 및 포름알데히드 제거능을 가지는 필터.Trientine or a trientine derivative represented by the following Chemical Formula 1, a cyclne or cycline derivative represented by the following Chemical Formula 2, or at least one selected from a cyclam or a cyclam derivative represented by the following Chemical Formula 3 as an active ingredient , Heavy metal and formaldehyde filter.
    [화학식 1][Formula 1]
    Figure PCTKR2018016802-appb-I000044
    Figure PCTKR2018016802-appb-I000044
    [화학식 2][Formula 2]
    Figure PCTKR2018016802-appb-I000045
    Figure PCTKR2018016802-appb-I000045
    [화학식 3][Formula 3]
    Figure PCTKR2018016802-appb-I000046
    Figure PCTKR2018016802-appb-I000046
    (상기 식들에서, R1, R2, R3, R4, R5 및 R6은 각각 독립적으로 수소, -R7-COOH 또는 이들의 염이고, R7은 C1~C5의 지방족, 치환되거나 치환되지 않은 방향족 고리, 또는 복소환 6원자 또는 5원자 고리이다.)(In the above formula, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen, -R 7 -COOH or a salt thereof, R 7 is C 1 ~C 5 aliphatic, A substituted or unsubstituted aromatic ring, or a heterocyclic 6-membered or 5-membered ring.)
  2. 제1항에 있어서,According to claim 1,
    상기 유효성분은 하기 화학식 1a의 트리엔틴, 화학식 2a의 사이클렌, 화학식 3a의 사이클람 또는 이들의 염 중에서 선택되는 것인, 중금속 및 포름알데히드 제거능을 가지는 필터.The active ingredient is a filter having a heavy metal and formaldehyde removal ability, which is selected from trientine of Formula 1a, cyclene of Formula 2a, cyclam of Formula 3a or salts thereof.
    [화학식 1a][Formula 1a]
    Figure PCTKR2018016802-appb-I000047
    Figure PCTKR2018016802-appb-I000047
    [화학식 2a][Formula 2a]
    Figure PCTKR2018016802-appb-I000048
    Figure PCTKR2018016802-appb-I000048
    [화학식 3a][Formula 3a]
    Figure PCTKR2018016802-appb-I000049
    Figure PCTKR2018016802-appb-I000049
  3. 제1항에 있어서,According to claim 1,
    상기 트리엔틴 유도체는 하기 화학식 1b 내지 1d로 표시되는 화합물 또는 이들의 염 중에서 선택되는 것인, 중금속 및 포름알데히드 제거능을 가지는 필터.The trientine derivative is a filter having the ability to remove heavy metals and formaldehyde, which is selected from compounds represented by the following Chemical Formulas 1b to 1d or salts thereof.
    [화학식 1b][Formula 1b]
    Figure PCTKR2018016802-appb-I000050
    Figure PCTKR2018016802-appb-I000050
    [화학식 1c][Formula 1c]
    Figure PCTKR2018016802-appb-I000051
    Figure PCTKR2018016802-appb-I000051
    [화학식 1d][Formula 1d]
    Figure PCTKR2018016802-appb-I000052
    Figure PCTKR2018016802-appb-I000052
    (상기 식들에서, R8, R9는 각각 독립적으로 수소 또는 C1~C4의 알킬기이고, X는 산소(O), 황(S) 또는 질소(N)이다.)(In the above formulas, R 8 and R 9 are each independently hydrogen or an alkyl group of C 1 to C 4 , and X is oxygen (O), sulfur (S) or nitrogen (N).)
  4. 제1항에 있어서,According to claim 1,
    상기 사이클렌 유도체는 하기 화학식 2b 내지 2d로 표시되는 화합물 또는 이들의 염 중에서 선택되는 것인, 중금속 및 포름알데히드 제거능을 가지는 필터.The cyclic derivative is a filter having a heavy metal and formaldehyde removal ability, which is selected from compounds represented by the following formulas 2b to 2d or salts thereof.
    [화학식 2b][Formula 2b]
    Figure PCTKR2018016802-appb-I000053
    Figure PCTKR2018016802-appb-I000053
    [화학식 2c][Formula 2c]
    Figure PCTKR2018016802-appb-I000054
    Figure PCTKR2018016802-appb-I000054
    [화학식 2d][Formula 2d]
    Figure PCTKR2018016802-appb-I000055
    Figure PCTKR2018016802-appb-I000055
    (상기 식들에서, R8, R9는 각각 독립적으로 수소 또는 C1~C4의 알킬기이고, X는 산소(O), 황(S) 또는 질소(N)이다.)(In the above formulas, R 8 and R 9 are each independently hydrogen or an alkyl group of C 1 to C 4 , and X is oxygen (O), sulfur (S) or nitrogen (N).)
  5. 제1항에 있어서,According to claim 1,
    상기 사이클람 유도체는 하기 화학식 3b 내지 3d로 표시되는 화합물 또는 이들의 염 중에서 선택되는 것인, 중금속 및 포름알데히드 제거능을 가지는 필터.The cyclam derivative is a filter having a heavy metal and formaldehyde removal ability, which is selected from compounds represented by the following formulas 3b to 3d or salts thereof.
    [화학식 3b][Formula 3b]
    Figure PCTKR2018016802-appb-I000056
    Figure PCTKR2018016802-appb-I000056
    [화학식 3c][Formula 3c]
    Figure PCTKR2018016802-appb-I000057
    Figure PCTKR2018016802-appb-I000057
    [화학식 3d][Formula 3d]
    Figure PCTKR2018016802-appb-I000058
    Figure PCTKR2018016802-appb-I000058
    (상기 식들에서, R8, R9는 각각 독립적으로 수소 또는 C1~C4의 알킬기이고, X는 산소(O), 황(S) 또는 질소(N)이다.)(In the above formulas, R 8 and R 9 are each independently hydrogen or an alkyl group of C 1 to C 4 , and X is oxygen (O), sulfur (S) or nitrogen (N).)
  6. 제1항에 있어서,According to claim 1,
    상기 트리엔틴 유도체는 하기 화학식 1e 내지 화학식 1h로 표시되는 화합물 또는 이들의 염 중에서 선택되는 것인, 중금속 및 포름알데히드 제거능을 가지는 필터.The trientine derivative is a filter having a heavy metal and formaldehyde removal ability, which is selected from compounds represented by the following Chemical Formulas 1e to 1h or salts thereof.
    [화학식 1e][Formula 1e]
    Figure PCTKR2018016802-appb-I000059
    Figure PCTKR2018016802-appb-I000059
    [화학식 1f][Formula 1f]
    Figure PCTKR2018016802-appb-I000060
    Figure PCTKR2018016802-appb-I000060
    [화학식 1g][Formula 1g]
    Figure PCTKR2018016802-appb-I000061
    Figure PCTKR2018016802-appb-I000061
    [화학식 1h][Formula 1h]
    Figure PCTKR2018016802-appb-I000062
    Figure PCTKR2018016802-appb-I000062
  7. 제1항에 있어서,According to claim 1,
    상기 사이클렌 유도체는 하기 화학식 2e 내지 화학식 2h로 표시되는 화합물 또는 이들의 염 중에서 선택되는 것인, 중금속 및 포름알데히드 제거능을 가지는 필터.The cyclic derivative is a filter having a heavy metal and formaldehyde removal ability, which is selected from the compounds represented by the following formulas 2e to 2h or salts thereof.
    [화학식 2e][Formula 2e]
    Figure PCTKR2018016802-appb-I000063
    Figure PCTKR2018016802-appb-I000063
    [화학식 2f][Formula 2f]
    Figure PCTKR2018016802-appb-I000064
    Figure PCTKR2018016802-appb-I000064
    [화학식 2g][Formula 2g]
    Figure PCTKR2018016802-appb-I000065
    Figure PCTKR2018016802-appb-I000065
    [화학식 2h][Formula 2h]
    Figure PCTKR2018016802-appb-I000066
    Figure PCTKR2018016802-appb-I000066
  8. 제1항에 있어서,According to claim 1,
    상기 사이클람 유도체는 하기 화학식 3e 내지 화학식 3h로 표시되는 화합물 또는 이들의 염 중에서 선택되는 것인, 중금속 및 포름알데히드 제거능을 가지는 필터.The cyclam derivative is a filter having a heavy metal and formaldehyde removal ability, which is selected from compounds represented by the following formulas 3e to 3h or salts thereof.
    [화학식 3e][Formula 3e]
    Figure PCTKR2018016802-appb-I000067
    Figure PCTKR2018016802-appb-I000067
    [화학식 3f][Formula 3f]
    Figure PCTKR2018016802-appb-I000068
    Figure PCTKR2018016802-appb-I000068
    [화학식 3g][Formula 3g]
    Figure PCTKR2018016802-appb-I000069
    Figure PCTKR2018016802-appb-I000069
    [화학식 3h][Formula 3h]
    Figure PCTKR2018016802-appb-I000070
    Figure PCTKR2018016802-appb-I000070
  9. 제1항 내지 제8항 중 어느 한 항에 있어서,The method according to any one of claims 1 to 8,
    상기 트리엔틴 또는 트리엔틴 유도체, 사이클렌 또는 사이클렌 유도체, 사이클람 또는 사이클람 유도체 성분은 필터 전체 중량에 대하여 0.001 ~ 5.0 중량%로 함유되는 것을 특징으로 하는, 중금속 및 포름알데히드 제거능을 가지는 필터.The trientine or trientine derivative, cyclene or cycline derivative, cyclam or cyclam derivative component is characterized in that contained in 0.001 to 5.0% by weight relative to the total weight of the filter, having a heavy metal and formaldehyde removal ability filter.
  10. 제1항에 있어서,According to claim 1,
    상기 필터는 공기청정용 필터, 에어컨 필터로 이용되는 것인, 중금속 및 포름알데히드 제거능을 가지는 필터.The filter is used as a filter for air cleaning, air conditioning filter, a filter having a heavy metal and formaldehyde removal ability.
  11. 제1항에 있어서,According to claim 1,
    상기 필터는 담배 필터로 이용되는 것인, 중금속 및 포름알데히드 제거능을 가지는 필터.The filter is used as a cigarette filter, a filter having a heavy metal and formaldehyde removal ability.
  12. 제10항의 담배 필터를 포함하는 필터 담배.A filter cigarette comprising the cigarette filter of claim 10.
  13. 제1항에 따른 필터를 포함하는 마스크.A mask comprising the filter according to claim 1.
PCT/KR2018/016802 2018-12-27 2018-12-27 Filter having heavy metal and formaldehyde removal capability WO2020138551A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992017403A1 (en) * 1991-04-05 1992-10-15 Brigham Young University Support bonded polyalkylene-polyamine-poly(carboxylic acid) and extraction of metal ions therewith
CN101890263A (en) * 2010-06-17 2010-11-24 佛山市顺德区阿波罗环保器材有限公司 Filter material for removing aldehydes
CN103357277A (en) * 2013-07-24 2013-10-23 浙江师范大学 Ultrafiltration membrane with heavy metal ion adsorption function, and preparation method thereof
CN104445469A (en) * 2014-12-18 2015-03-25 石泰山 Method for treating phosphorus/phosphine-containing electroplating wastewater by utilizing electroplating sludge
CN105753223A (en) * 2016-05-12 2016-07-13 东莞市联洲知识产权运营管理有限公司 Treatment method of electroplating effluent containing heavy metal ions

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992017403A1 (en) * 1991-04-05 1992-10-15 Brigham Young University Support bonded polyalkylene-polyamine-poly(carboxylic acid) and extraction of metal ions therewith
CN101890263A (en) * 2010-06-17 2010-11-24 佛山市顺德区阿波罗环保器材有限公司 Filter material for removing aldehydes
CN103357277A (en) * 2013-07-24 2013-10-23 浙江师范大学 Ultrafiltration membrane with heavy metal ion adsorption function, and preparation method thereof
CN104445469A (en) * 2014-12-18 2015-03-25 石泰山 Method for treating phosphorus/phosphine-containing electroplating wastewater by utilizing electroplating sludge
CN105753223A (en) * 2016-05-12 2016-07-13 东莞市联洲知识产权运营管理有限公司 Treatment method of electroplating effluent containing heavy metal ions

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