CN107266445A - The piperidines and the preparation method of the triazole tin complex of pyrido 1,2,3 acted on PVC stabilizer - Google Patents
The piperidines and the preparation method of the triazole tin complex of pyrido 1,2,3 acted on PVC stabilizer Download PDFInfo
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- WLDVFUGWZBUREX-UHFFFAOYSA-N CC(C)(C)OC(N(CC1)CC(C(Cl)=C2)=C1N(C)C2=O)=O Chemical compound CC(C)(C)OC(N(CC1)CC(C(Cl)=C2)=C1N(C)C2=O)=O WLDVFUGWZBUREX-UHFFFAOYSA-N 0.000 description 2
- TXWQWZUOYAQDRV-UHFFFAOYSA-N CCOC(c(c(O)nc(CC1)c2CN1C(OC(C)(C)C)=O)c2O)=O Chemical compound CCOC(c(c(O)nc(CC1)c2CN1C(OC(C)(C)C)=O)c2O)=O TXWQWZUOYAQDRV-UHFFFAOYSA-N 0.000 description 1
- QQPCDZDICBNUQZ-UHFFFAOYSA-N CNC(NC(CCNC1)=C1C1Cl)=C1N Chemical compound CNC(NC(CCNC1)=C1C1Cl)=C1N QQPCDZDICBNUQZ-UHFFFAOYSA-N 0.000 description 1
- XZVQGRAKQPXRSK-UHFFFAOYSA-N O=Sc1ccccc1 Chemical compound O=Sc1ccccc1 XZVQGRAKQPXRSK-UHFFFAOYSA-N 0.000 description 1
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
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Abstract
The invention discloses the preparation method of a kind of piperidines acted on PVC stabilizer and the triazole tin complex of pyrido 1,2,3, belong to technical field of organic synthesis.Technical scheme main points are：
Description
Technical field
The invention belongs to pharmaceutical chemical synthesis technical field, and in particular to a kind of piperidines acted on PVC stabilizer
And the preparation method of pyrido 1,2,3- triazoles-tin complex.
Background technology
Polyvinyl chloride (abbreviation PVC) is one of five big general-purpose plastics, with its cheap price and very prominent harmony
Can and as very good material, be also plastic applications ancient and active kind in history, its global yield is only second to gather
Ethene occupies second.China is one of big producer of polyvinyl chloride resin, and domestic PVC industry took by the development of more than 50 years
Rapid progress, the current country possesses family more than 100 of Production of PVC enterprise, and production capacity occupy first in synthetic resin at home
Position.
When general PVC is generally heated to more than 130 DEG C, just start to discharge HCl, because in manufacture PVC process
In, because Auto-oxidation reaction, chain termination reaction and the copolyreaction of micro amount of oxygen and some not yet clear and definite side reactions are generated
Unstable C-Cl keys, and then HCl is discharged by thermal decomposition, and HCl can be decomposed to PVC continuation and be played catalytic action, be made
PVC is finally converted to containing undersaturated conjugated double bond structures (polyenoid sequence), such consecutive reaction, has finally resulted in big point
Occurs long polyenoid sequence in subchain, when the double key number on macromolecular chain is more than 6, PVC will change colour.
Therefore, should possess prophylactic function and passivation as PVC heat stabilizer.Wherein prophylactic function includes two sides
Face, is on the one hand to absorb the HCl that PVC thermal degradations are discharged, and is on the other hand to eliminate the unstable chlorine atoms of PVC, so as to prevent
HCl generation；Passivation is the material of PVC performances of eliminating the effects of the act, and its method is that heat stabilizer enters with polyenoid sequence compound
Row addition reaction, makes long polyenoid sequence compound shorten and (reduce conjugated double bond number).At present, in the market action effect is best
Be organic tin heat stabilizer, be most promising heat stabilizer, especially transparent PVC preparation in application it is more wide
It is general.It mainly includes stannous methide, the soap of di-n-butyl tin and dioctyltin, maleate, mercaptides, mercapto
The types such as soap.Organic tin heat stabilizer has the advantages that good heat endurance, compatibility and the transparency, but such
Heat stabilizer is all liquid, not very convenient in terms of transport, storage.
In recent years, heterocyclic compound is because structure is changeable, active high, toxicity is low and turns into the master of medicine and agricultural chemicals innovation
Stream, plurality of new varieties just continuously put goods on the market, and study on the synthesis is more towards baroque condensed hetero ring, double miscellaneous
Ring and poly-heterocyclic compounds.Piperidine compounds are the nitrogen-containing heterocycle compounds with good biological activity, are widely used in medicine
With the study on the synthesis of agricultural chemicals.Piperidines is mainly used in synthesis medicine, agricultural chemicals and rubber chemicals, is mainly used in synthesizing rice in pesticide industry
Field herbicidal dimepiperate, is a kind of selective non-hormone-type thiocarbamic acid class herbicide, very with development prospect.
Pharmaceuticals industry is used to synthesize medicine for digestive system hydrochloric acid acetyl Roxatidine, cardiovascular disease medicine Dipyridmole etc..In rubber
Auxiliary industry is used to synthesize the super vulcanization accelerator bis-pentamethylenethiuram tetrasulfide of thiurams, dithiocar-bamate
Super accelerator pentamethylene aminodithioformic acid piperidinium salt of class etc..Other piperidines can also synthesize various new fine chemistry industry
Intermediate, many products belong to the intermediate of small tonnage newly developed, the medicine of high added value, agricultural chemicals and auxiliary agent, such as 2- first
Phenylpiperidines, 3- aminomethylpiperidines, 4- hydroxy piperidines etc..Pyridine is also a kind of important nitrogen heterocyclic ring, because it has life well
Thing activity is widely used in medical research.For example, its derivative can be adjusted as 5HT2A receptor antagonists, extracellular signal
Save kinases inhibitor, mammal P2X7 conditioning agents, and with anti-breast cancer cell MDA-MB-231 proliferation activities and
Suppress the propagation of hepatocellular carcinoma H22.1,2,3- triazole compound has the structure of many five yuan of heteroaromatics of nitrogen, and its structure is made
For a kind of important active structure unit, show a variety of important bioactivity, for example antibacterium, treating tuberculosis, it is antitumor,
Antiviral, anti-inflammatory and analgesia etc..The common concern of people is constantly subjected to for a long time, is obtained in agricultural chemicals, medicine and chemical field
It is widely applied.
We utilize piperidines and 1, and 2,3- triazoles also have nitrogen-atoms, and nitrogen-atoms is easy to the principle combined with hydrogen chloride,
The a series of piperidines with PVC stabilizer function and pyrido 1,2,3- triazoles-tin complex have been synthesized, and have carried out phase
Close detection.
The content of the invention
Present invention solves the technical problem that there is provided, a kind of synthetic method is simple, molecular structure it is novel have PVC steady
Determine the piperidines and pyrido 1,2,3- triazoles-tin complex preparation method of agent effect.
The present invention adopts the following technical scheme that a kind of new acts on PVC stabilizer to solve above-mentioned technical problem
Piperidines and pyrido 1,2,3- triazoles-tin complex molecule structure be：
The present invention adopts the following technical scheme that a kind of new acts on PVC stabilizer to solve above-mentioned technical problem
Piperidines and pyrido 1, the preparation method of 2,3- triazoles-tin complex, it is characterised in that concretely comprise the following steps：
A, N-Boc-4- piperidones and dimethyl carbonate react in the presence of potassium tert-butoxide obtains N-Boc-3- formic acid first
Ester -4- piperidones
B, N-Boc-3- methyl formate -4- piperidones are under ammonium acetate effect, and ketone carbonyl redox is changed into amino
Compound N-Boc-3- methyl formate -4- amino -3- alkene-piperidines
C, N-Boc-3- methyl formate -4- amino -3- alkene-piperidines and chloroformyl ethyl acetate take under TEA effects
Generation reaction obtains compound N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines
D, N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines occur in the presence of potassium tert-butoxide
Intramolecular cyclization obtains compoundThen the compound carries out intramolecular in acid condition
Hydrogen migration and carbonyl reduction obtain compound
E、Under strongly acidic conditions, ester group and Boc groups are sloughed in heating, obtain compound
F、Under POCl3 effect, hydroxyl is replaced by chlorine obtains compound
G、Chloro carbon-to-nitrogen double bon is changed into amido link under concentrated hydrochloric acid effect and obtain compound
H、In the basic conditions, Boc amido protectings are carried out and obtains compound
I、Under cesium carbonate effect compound is obtained with iodomethane reaction
J、The hydrogenated reduction of carbon-carbon double bond is set to obtain compound under Pd/C effects
K、Compound is obtained with azido compound reaction
L、Slough Boc groups and methyl obtains compound
M、Obtained with p-aminobenzene sulfonic acid reaction
N、With stannous chloride coordinate obtaining compound
Further limit, step A detailed process is：In reaction bulb, 1eq N-Boc-4- piperidones is added to
In the toluene of 10V volumes, 2eq dimethyl carbonate and 2eq potassium tert-butoxide are added, 70 DEG C of reaction 1h is heated to, is cooled to
Room temperature, adds water and is quenched, and it is 7 to adjust reaction solution pH with 1mol/L HCl, ethyl acetate extraction, after anhydrous sodium sulfate drying, is spin-dried for
Obtain yellow oil N-Boc-3- methyl formate -4- piperidones
Further limit, step B detailed process is：1eq N-Boc-3- methyl formate -4- piperidones is added to 10
In the methanol of times volume, 3eq ammonium acetate is added, reaction is stayed overnight, be spin-dried for methanol, add the water of 3 times of volumes, dichloromethane extraction
Anhydrous sodium sulfate drying is used after extracting reaction solution, red oily liquids N-Boc-3- methyl formate -4- amino -3- is obtained after being spin-dried for
Alkene-piperidines
Further limit, step C detailed process is：By 1eq N-Boc-3- methyl formate -4- amino -3- alkene-piperidines
In the DCM for being added to 8 times of volumes, 1.05eq TEA is added, 10 DEG C are cooled to, 1.05eq 4- chloromethane ethyl acetoacetic acid second is added dropwise
Ester, room temperature reaction is stayed overnight, and adds the DCM dilute reaction solutions of 8 times of volumes, twice, anhydrous sodium sulfate drying is spin-dried for both obtaining for washing
Red oil product N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines
Further limit, step D detailed process is：1eq N-Boc-3- methyl formate -4- carbamyl acetic acid second
Ester -3- alkene-piperidines is added in the THF of 10 times of volumes, then is added portionwise 2.0eq t-BuOK, reaction temperature control less than
25 DEG C, frozen water is added after reaction 1h and is quenched, it is 3 to adjust reaction solution pH with 2mol/L HCl, filtering, and it is white that vacuum drying obtains class
Color solid product
Further limit, step E detailed process is：In 10eq 6mol/L HCl solution, it is added portionwise 1.0eq's100 DEG C are heated to, reaction is stayed overnight, are spin-dried for reaction dissolvent, then washed with ether, is dried in vacuo
Obtain off-white powder
Further limit, step F detailed process is：To 5eq POCl3In be added portionwise 1.0eq's
100 DEG C are heated to, reaction is stayed overnight, are spin-dried for POCl3Obtain Red oil product
Further limit, step G detailed process is：It is added to the 1,4- dioxies six of 4 times of volumes
In ring, the concentrated hydrochloric acid of 4 times of volumes is added, 100 DEG C are heated to, back flow reaction 2 days is spin-dried for adding the second of 10 times of volumes after solvent
Acetoacetic ester, is washed three times, is dried and is obtained brown solid after being spin-dried for
Further limit, step H detailed process is：1eq'sIt is added to the 1,4- of 10 times of volumes
In dioxane and the water of 10 times of volumes, then 3.0eq sodium carbonate and 1.5eq (Boc) is added portionwise2O, reacts at room temperature 10h
Afterwards, filter, then wash with ethyl acetate reaction solution is extracted with ethyl acetate after filter cake, then washed with sodium chloride solution, dried, revolved
Reaction solution is obtained
Further limit, step I detailed process is：1.0eq'sIt is added to 10 times of volumes
DMF in, add 1.5eq Cs2CO3, 1.3eq KI, room temperature reaction stays overnight, and adds frozen water and reaction solution, acetic acid is quenched
Ethyl ester extractive reaction liquid, sodium chloride solution washing, dries, is spin-dried for, then is beaten with ether, filters, and it is solid that vacuum drying obtains white
Body
Further limit, step J detailed process is：In autoclave, by 1.0eq'sAdd
To the methanol of 10 times of volumes, a certain amount of Pd/C is passed through hydrogen, reacting kettle inner pressure is reached 0.2MPa, is heated to 50 DEG C, returns
Stream reaction 5h, TLC monitoring raw material reaction is complete, and filtering reacting liquid is spin-dried for after solvent obtaining brown solid
Further limit, step K detailed process is：In reaction bulb, 1.0eq'sIt is added to
In the tert-butyl alcohol of 20 times of volumes, 3.0eq potassium carbonate and 1.2eq TMSN are added3, react at room temperature after a period of time,
TLC monitoring raw material reactions are complete, obtain compound
Further limit, step L detailed process is：In reaction bulb, by 1.0eq'sPlus
Enter in the HCl/1 to the methanol of 10 times of volumes and the 12mol/L of 10 volumes, 4- dioxane, room temperature reaction is stayed overnight, and is spin-dried for, second
Ether is washed, and is obtained
Further limit, step M detailed process is：In reaction bulb,It is added in DMF,
Triethylamine and p-aminobenzene sulfonic acid are added, 70 DEG C are heated to, reaction a period of time obtains compound
Further limit, step N detailed process is：Nitrogen is passed through into the ultrasonic response container for being provided with agitating device
Gas, then add dissolved withDichloromethane solution, add after ammoniacal liquor, in 25 DEG C to super
The methanol solution dissolved with stannous chloride is added dropwise in sound wave reaction vessel, opens agitating device during dropwise addition and ultrasonic wave is filled
Put, the setpoint frequency of ultrasonic generator is 80KHz, drip rear solution for clear state, stop stirring, keep ultrasonic wave
Generating means works on, and is cooled to 0 DEG C of standing reaction solution, opens the steam vent on ultrasonic response container, keep what is be passed through
Nitrogen is discharged from steam vent, nitrogen is discharged ultrasonic response container with reaction dissolvent, there is crystallization after clear crystal precipitation, 5h
Completely, suction filtration reaction solution, filter cake is washed repeatedly with methanol to wash away unnecessary stannous chloride, and filter cake is obtained after drying at room temperature
The new piperidines acted on PVC stabilizer of the present invention and pyrido 1,2,3- triazoles-tin complex
Synthetic route be：
The present invention has synthesized a kind of piperidines and pyrido 1,2,3- triazoles-tin complex and has carried out PVC stabilizer survey
Examination, it is found that the complex has good PVC stabilizer function.
Embodiment
The above to the present invention is described in further details by the following examples, but this should not be interpreted as to this
The scope for inventing above-mentioned theme is only limitted to following embodiment, and all technologies realized based on the above of the present invention belong to this hair
Bright scope.
Embodiment 1
In reaction bulb, N-Boc-4- piperidones 20g (0.1mol) is added in toluene 200mL, carbonic acid two is added
Methyl esters 18g (0.2mol) and potassium tert-butoxide 22g (0.2mol), is heated to 70 DEG C of reaction 1h, is cooled to room temperature, the 100mL that adds water quenches
Go out, it is 7 to adjust reaction solution pH with 1mol/L HCl, ethyl acetate extraction, after anhydrous sodium sulfate drying, be spin-dried for obtaining yellow oil
Shape thing N-Boc-3- methyl formate -4- piperidones 25g；1HNMR(400MHz,CD3Cl)δ:3.81 (s, 1H), 3.71 (d, J=
8.4Hz, 1H), 3.68 (d, J=8.4Hz, 1H), 3.45 (s, 3H), 3.07-3.05 (m, 2H), 2.76-2.73 (m, 2H), 1.37
(s,9H).MS-ESI(m/z):258.3[M+H+]。
Embodiment 2
In reaction bulb, N-Boc-3- methyl formate -4- piperidones 25g (0.1mol) are added in methanol 300mL, then
Ammonium acetate 22g (0.3mol) is added, reaction is stayed overnight, TLC monitoring raw material reactions are complete, are spin-dried for methanol, water 900mL added, with two
Chloromethanes 300mL extractive reactions liquid three times, merges and anhydrous sodium sulfate drying is used after organic phase, red oily liquids is obtained after being spin-dried for
N-Boc-3- methyl formate -4- amino -3- alkene-piperidines 25g；1HNMR(400MHz,CD3Cl)δ:8.56(s,2H),3.93(s,
2H),3.77(s,3H),3.57-3.55(m,2H),2.16-2.13(m,2H),1.37(s,9H).MS-ESI(m/z):257.3[M
+H+]。
Embodiment 3
In reaction bulb, N-Boc-3- methyl formate -4- amino -3- alkene-piperidines 26g (0.1mol) is added to dichloromethane
In alkane 200mL, TEA11g (0.11mol) is added, 10 DEG C are cooled to, 4- chloroformyl ethyl acetate 16g is slowly added dropwise
(0.105mol), room temperature reaction is stayed overnight, and TLC monitoring raw material reactions are complete, add dichloromethane 200mL dilute reaction solutions, water
Wash twice, anhydrous sodium sulfate drying, be spin-dried for both obtaining Red oil product N-Boc-3- methyl formate -4- carbamyl acetic acid second
Ester -3- alkene-piperidines 25g；1HNMR(400MHz,CD3Cl)δ:4.71(s,2H),3.93(s,2H),3.79(s,3H),3.57-
3.55(m,2H),3.53(s,2H),2.16-2.13(m,2H),1.37(s,9H),1.29(s,3H).MS-ESI(m/z):371.4
[M+H+]。
Embodiment 4
In reaction bulb, N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines 37g (0.1mol)
It is added in THF400mL, then t-BuOK 23g (0.2mol) is added portionwise, reaction temperature control is reacted after 1h less than 25 DEG C
Add frozen water 300mL to be quenched, it is 3 to adjust reaction solution pH with 2mol/L HCl, and filtering, vacuum drying obtains off-white powder production
Product32g；1H NMR(400MHz,DMSO-d6)δ:11.51(s,1H),5.35(s,1H),
4.71 (s, 2H), 4.33 (d, J=4.0Hz, 2H), 3.66-3.62 (m, 2H), 3.25 (d, J=12.0Hz, 2H), 1.41-1.39
(m,9H),1.33-1.32(m,3H)。
Embodiment 5
In reaction bulb, the HCl solution 200mL in 6mol/L is added, then be added portionwise
34g (0.1mol), is heated to 100 DEG C, reaction is stayed overnight, and is spin-dried for reaction dissolvent, then is washed with ether, and vacuum drying obtains off-white color
Solid15g；1H NMR(400MHz,DMSO-d6)δ:11.47(s,1H),5.95(s,1H),5.41(s,
1H), 3.86-3.85 (m, 2H), 3.71 (d, J=12.0Hz, 2H), 3.11-3.09 (m, 2H), 1.90 (s, 1H).
Embodiment 6
In closed reaction bulb, it is added portionwise into POCl3 50g (0.5mol)16g
(0.1mol), is slowly heated to 100 DEG C, reaction is stayed overnight, and after TLC monitoring raw material reactions completely, vacuum is spin-dried for POCl3 and obtained
Red oil product16g；1H NMR(400MHz,DMSO-d6)δ:7.61(s,1H),3.81(s,2H),
3.37 (d, J=12.0Hz, 2H), 3.13-3.12 (m, 2H), 1.87 (s, 1H).
Embodiment 7
In the reaction bulb with thermometer and stirring,20g is added to 1,4- dioxane
In 100mL, concentrated hydrochloric acid 100mL is slow added into, 100 DEG C are heated to, back flow reaction 2 days, TLC is monitored after raw material reaction completely,
It is spin-dried for solvent and concentrate is added the ethyl acetate of 10 times of volumes, washes three times, separate organic phase, dry and obtain palm fibre after being spin-dried for
Color solid17g；1H NMR(400MHz,CDCl3)δ:8.17(s,1H),6.62(s,1H),3.35(s,2H),
2.96 (d, J=12.0Hz, 2H), 2.07-2.05 (m, 2H) .MS-ESI (m/z):185.6[M+H+]。
Embodiment 8
In reaction bulb,18g (0.1mol) is added to 1,4- dioxane 200mL and water 200mL
In, then sodium carbonate 30g (0.3mol) and (Boc) is added portionwise2After O 33g (0.15mol), room temperature reaction 10h, TLC monitoring is former
Material reaction is complete, filtering reacting liquid, then is washed with ethyl acetate 100mL after filter cake with ethyl acetate 200mL extractive reactions liquid three
It is secondary, then washed with sodium chloride solution, dry, rotation reaction solution is obtained20g；1H NMR(400MHz,DMSO-
d6)δ:6.61 (s, 1H), 3.93 (s, 2H), 3.54 (s, 3H), 3.57 (d, J=12.0Hz, 2H), 2.07-2.05 (m, 2H),
1.39(s,9H)。
Embodiment 9
In reaction solution,28g (0.1mol) is added in DMF 300mL, adds carbonic acid
Caesium 50g (0.15mol), iodomethane 20g (0.13mol), room temperature reaction is stayed overnight, and TLC monitoring raw material reactions are complete, add frozen water
Reaction solution is quenched in 100mL, and ethyl acetate 200mL extractive reactions liquid three times, saturated nacl aqueous solution 200mL washing reaction liquids are done
It is dry, it is spin-dried for, then be beaten with ether, filter, vacuum drying obtains white solid26g；1H NMR
(400MHz,DMSO-d6)δ:6.61 (s, 1H), 3.94 (s, 2H), 3.54 (s, 3H), 3.55 (d, J=8.0Hz, 2H), 2.07-
2.05(m,2H),1.38(s,9H).MS-ESI(m/z):299.8[M+H]+。
Embodiment 10
, will in autoclave30g (0.1mol) is added in methanol 300mL, adds Pd/
C6g, is passed through hydrogen, reacting kettle inner pressure is reached 0.2MPa, is heated to 50 DEG C, back flow reaction 5h, TLC monitoring raw material has reacted
Entirely, filtering reacting liquid, is spin-dried for after solvent obtaining solid28g；1H NMR(400MHz,DMSO-d6)δ:
4.38 (s, 1H), 3.96 (s, 2H), 3.57 (s, 2H), 3.31 (d, J=8.0Hz, 3H), 2.59-2.57 (m, 2H), 2.07-
2.05(m,2H),1.37(s,9H).MS-ESI(m/z):301.8[M+H]+。
Embodiment 11
In reaction bulb,30g (0.1mol) is added in tert-butyl alcohol 400mL, adds carbon
Sour K42 g (0.3mol) and TMSN314g (0.12mol), reacts after a period of time at room temperature, and TLC monitoring raw materials have reacted
Entirely, reaction solution is poured into water 500mL, with ethyl acetate 200mL extractive reactions liquid three times, merges organic phase, solvent is evaporated off and obtains
To compound29g；1H NMR(400MHz,DMSO-d6)δ:12.5(s,1H),5.44(s,1H),
(s, the 9H) .MS- of 3.97 (s, 2H), 3.51-3.50 (m, 2H), 3.31 (d, J=8.0Hz, 3H), 2.07-2.06 (m, 2H), 1.37
ESI(m/z):326.7[M+H]+。
Embodiment 12
, will in reaction bulb32g (0.1mol) is added to methanol 300mL's and 12mol/L
In HCl/1,4- dioxane 200mL, room temperature reaction is stayed overnight, and TLC monitoring raw material reactions are complete, are spin-dried for, ether washing concentrate,
Obtain17g；1H NMR(400MHz,DMSO-d6)δ:12.1(s,1H),5.46(s,1H),4.02(s,
2H), 3.31 (d, J=8.0Hz, 2H), 2.95-2.93 (m, 2H), 2.07-2.06 (m, 2H) .MS-ESI (m/z) 212.6 [M+H
]+。
Embodiment 13
In reaction bulb,21g (0.1mol) is added in DMF 200mL, adds triethylamine
30mL and p-aminobenzene sulfonic acid 33g (0.2mol), is heated to 70 DEG C, reaction a period of time obtains compound31g；1H NMR(400MHz,DMSO-d6)δ:12.5(s,1H),7.63-7.62(m,
2H), 7.12-7.11 (m, 2H), 6.27 (m, 2H), 5.46 (s, 1H), 4.01 (s, 1H), 3.31 (d, J=8.0Hz, 2H),
2.95-2.93(m,2H),2.07-2.06(m,2H).MS-ESI(m/z):367.8[M+H]+。
Embodiment 14
Nitrogen is passed through into the ultrasonic response container for being provided with agitating device, is then added dissolved with compound51g dichloromethane solution 500mL, is added after ammoniacal liquor 100mL, in 25 DEG C to ultrasound
The methanol solution 500mL dissolved with stannous chloride 50g is slowly added dropwise in ripple reaction vessel, agitating device is opened during dropwise addition and super
Sound wave generating device, the setpoint frequency of ultrasonic generator is 80KHz, drips rear solution for clear state, stops stirring,
Ultrasonic generator is kept to work on, slow cooling opens the exhaust on ultrasonic response container to 0 DEG C of standing reaction solution
Hole, keeps the nitrogen being passed through to be discharged from steam vent, nitrogen is discharged ultrasonic response container with a certain amount of reaction dissolvent, by
Gradually there is after clear crystal precipitation, 5h crystallization completely, suction filtration reaction solution, filter cake wash multiple to wash away unnecessary stannous with methanol
Salt, filter cake is obtained after drying at room temperature48g。
Embodiment 15
Heat stability testing
PVC material formula needed for detection, which is constituted, is：The adjacent benzene two of plasticizer of the PVC material of 100 parts by weight, 5 parts by weight
The stabilizer of formic acid dioctyl ester, the titanium dioxide of 3 parts by weight and certain part by weight, under the conditions of 180 DEG C in twin-screw extruder
Plasticate to discoloration, the length (time is longer, and explanation stabilizer effect is better) for the time undergone during observation color change is above-mentioned
It is as shown in the table per stabilizer addition used in portion PVC material.
As can be seen from the above table, obtained by the present inventionEffect
Effect has exceeded traditional lead compound stabilizer, calcium-zinc composite stabilizing agent and Methyl stannum mercaptide stabilizer stabilizer level.
Embodiment above describes general principle, principal character and the advantage of the present invention, the technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, the original for simply illustrating the present invention described in above-described embodiment and specification
Reason, under the scope for not departing from the principle of the invention, various changes and modifications of the present invention are possible, and these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (8)
1. the piperidines and pyrido 1 that are acted on PVC stabilizer, the preparation method of 2,3- triazoles-tin complex, its feature exist
In concretely comprising the following steps：
A, N-Boc-4- piperidones and dimethyl carbonate react in the presence of potassium tert-butoxide obtains N-Boc-3- methyl formates -4-
Piperidones；
B, N-Boc-3- methyl formate -4- piperidones are under ammonium acetate effect, and ketone carbonyl redox obtains compound into amino
N-Boc-3- methyl formate -4- amino -3- alkene-piperidines；
It is anti-that under TEA effects substitution occurs for C, N-Boc-3- methyl formate -4- amino -3- alkene-piperidines and chloroformyl ethyl acetate
Compound N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines should be obtained；
Molecule occurs in the presence of potassium tert-butoxide for D, N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene-piperidines
Interior cyclization obtains compoundThen the compound carries out intramolecular hydrogen turn in acid condition
Move and carbonyl reduction obtains compound
E、Under strongly acidic conditions, ester group and Boc groups are sloughed in heating, obtain compound
F、Under POCl3 effect, hydroxyl is replaced by chlorine obtains compound
G、Chloro carbon-to-nitrogen double bon is changed into amido link under concentrated hydrochloric acid effect and obtain compound
H、In the basic conditions, Boc amido protectings are carried out and obtains compound
I、Under cesium carbonate effect compound is obtained with iodomethane reaction
J、The hydrogenated reduction of carbon-carbon double bond is set to obtain compound under Pd/C effects
K、Compound is obtained with azido compound reaction
L、Slough Boc groups and methyl obtains compound
M、Obtained with p-aminobenzene sulfonic acid reaction
N、With stannous chloride coordinate obtaining compound
2. the piperidines according to claim 1 acted on PVC stabilizer and pyrido 1,2,3- triazoles-tin complex
Preparation method, it is characterised in that step A detailed process is：In reaction bulb, 1eq N-Boc-4- piperidones is added to
In the toluene of 10V volumes, 2eq dimethyl carbonate and 2eq potassium tert-butoxide are added, 70 DEG C of reaction 1h is heated to, is cooled to
Room temperature, adds water and is quenched, and it is 7 to adjust reaction solution pH with 1mol/L HCl, ethyl acetate extraction, after anhydrous sodium sulfate drying, is spin-dried for
Obtain yellow oil N-Boc-3- methyl formate -4- piperidones；Described step B detailed process is：By 1eq N-Boc-
3- methyl formate -4- piperidones is added in the methanol of 10 times of volumes, adds 3eq ammonium acetate, reaction is stayed overnight, and is spin-dried for first
Alcohol, adds and anhydrous sodium sulfate drying is used after the water of 3 times of volumes, dichloromethane extractive reaction liquid, red oily liquid is obtained after being spin-dried for
Body N-Boc-3- methyl formate -4- amino -3- alkene-piperidines；Described step C detailed process is：By 1eq N-Boc-3- first
Sour methyl esters -4- amino -3- alkene-piperidines is added in the DCM of 8 times of volumes, adds 1.05eq TEA, is cooled to 10 DEG C, dropwise addition
1.05eq 4- chloroformyl ethyl acetate, room temperature reaction is stayed overnight, and adds the DCM dilute reaction solutions of 8 times of volumes, is washed twice,
Anhydrous sodium sulfate drying, be spin-dried for both Red oil product N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene -
Piperidines；Described step D detailed process is：1eq N-Boc-3- methyl formate -4- carbamyl ethyl acetate -3- alkene -
Piperidines is added in the THF of 10 times of volumes, then 2.0eq t-BuOK is added portionwise, and reaction temperature control is reacted less than 25 DEG C
Add frozen water after 1h to be quenched, it is 3 to adjust reaction solution pH with 2mol/L HCl, and filtering, vacuum drying obtains off-white powder product
3. the piperidines according to claim 1 acted on PVC stabilizer and pyrido 1,2,3- triazoles-tin complex
Preparation method, it is characterised in that step E detailed process is：In 10eq 6mol/L HCl solution, 1.0eq is added portionwise
's100 DEG C are heated to, reaction is stayed overnight, are spin-dried for reaction dissolvent, then washed with ether, vacuum is done
It is dry to obtain off-white powderDescribed step F detailed process is：To 5eq POCl3In be added portionwise
1.0eq100 DEG C are heated to, reaction is stayed overnight, are spin-dried for POCl3Obtain Red oil productDescribed step G detailed process is：It is added to the 1,4- dioxies of 4 times of volumes
In six rings, the concentrated hydrochloric acid of 4 times of volumes is added, 100 DEG C are heated to, back flow reaction 2 days is spin-dried for 10 times of volumes of addition after solvent
Ethyl acetate, is washed three times, is dried and is obtained brown solid after being spin-dried for
4. the piperidines according to claim 1 acted on PVC stabilizer and pyrido 1,2,3- triazoles-tin complex
Preparation method, it is characterised in that step H detailed process is：1eq'sThe 1 of 10 times of volumes is added to,
In 4- dioxane and the water of 10 times of volumes, then 3.0eq sodium carbonate and 1.5eq (Boc) is added portionwise2O, room temperature reaction
After 10h, filtering, then wash with ethyl acetate reaction solution is extracted with ethyl acetate after filter cake, then washed with sodium chloride solution, it is dry
Dry, rotation reaction solution is obtainedDescribed step I detailed process is：1.0eq's
In the DMF for being added to 10 times of volumes, 1.5eq Cs is added2CO3, 1.3eq KI, room temperature reaction stays overnight, and adds frozen water
Reaction solution is quenched, ethyl acetate extractive reaction liquid, sodium chloride solution washing is dried, is spin-dried for, then is beaten with ether, is filtered, vacuum
It is dried to obtain white solid
5. the piperidines according to claim 1 acted on PVC stabilizer and pyrido 1,2,3- triazoles-tin complex
Preparation method, it is characterised in that step J detailed process is：In autoclave, by 1.0eq'sPlus
Enter the methanol to 10 times of volumes, a certain amount of Pd/C is passed through hydrogen, reacting kettle inner pressure is reached 0.2MPa, is heated to 50 DEG C,
Back flow reaction 5h, TLC monitoring raw material reaction is complete, and filtering reacting liquid is spin-dried for after solvent obtaining brown solidDescribed step K detailed process is：In reaction bulb, 1.0eq'sPlus
Enter into the tert-butyl alcohol of 20 times of volumes, add 3.0eq potassium carbonate and 1.2eq TMSN3, a period of time is reacted at room temperature
Afterwards, TLC monitors raw material reaction completely, obtains compound
6. the piperidines according to claim 1 acted on PVC stabilizer and pyrido 1,2,3- triazoles-tin complex
Preparation method, it is characterised in that step L detailed process is：In reaction bulb, by 1.0eq'sAdd
To 10 times of volumes methanol and 10 volumes 12mol/L HCl/1, in 4- dioxane, room temperature reaction is stayed overnight, and is spin-dried for, ether
Washing, is obtainedDescribed step M detailed process is：In reaction bulb,
It is added in DMF, adds triethylamine and p-aminobenzene sulfonic acid, is heated to 70 DEG C, reaction a period of time obtains compound
7. the piperidines according to claim 1 acted on PVC stabilizer and pyrido 1,2,3- triazoles-tin complex
Preparation method, it is characterised in that step N detailed process is：It is passed through into the ultrasonic response container for being provided with agitating device
Nitrogen, then add dissolved withDichloromethane solution, add ammoniacal liquor after, in 25 DEG C to
The methanol solution dissolved with stannous chloride is added dropwise in ultrasonic response container, agitating device is opened during dropwise addition and ultrasonic wave occurs
Device, the setpoint frequency of ultrasonic generator is 80KHz, drips rear solution for clear state, stops stirring, keeps ultrasound
Wave generating device works on, and is cooled to 0 DEG C of standing reaction solution, opens the steam vent on ultrasonic response container, keep being passed through
Nitrogen from steam vent discharge, make nitrogen with reaction dissolvent discharge ultrasonic response container, have after clear crystal precipitation, 5h analyse
Brilliant complete, suction filtration reaction solution, filter cake is washed with methanol repeatedly to wash away unnecessary stannous chloride, and filter cake is obtained after drying at room temperature
Arrive
8. the piperidines according to claim 1 acted on PVC stabilizer and pyrido 1,2,3- triazoles-tin complex
Preparation method, it is characterised in that the specific synthetic route in preparation process is：
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102558608A (en) * | 2010-12-27 | 2012-07-11 | 泰安市蓝天助剂有限公司 | Sebacic acid mercapto ethyl ester dimethyl tin heat stabilizing agent and preparation method thereof |
| CN105315574A (en) * | 2015-10-12 | 2016-02-10 | 浙江工业大学 | Calcium and zinc heat stabilizer for PVC and application of calcium and zinc heat stabilizer |
| CN106084294A (en) * | 2016-06-20 | 2016-11-09 | 河南师范大学 | A kind of beta diketone class organotin PVC heat stabilizer and preparation method thereof |
| CN106117263A (en) * | 2016-06-25 | 2016-11-16 | 安徽升华新奥特化工有限公司 | A kind of Methyl stannum mercaptide stabilizer of environmental protection |
-
2017
- 2017-06-05 CN CN201710411943.7A patent/CN107266445A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102558608A (en) * | 2010-12-27 | 2012-07-11 | 泰安市蓝天助剂有限公司 | Sebacic acid mercapto ethyl ester dimethyl tin heat stabilizing agent and preparation method thereof |
| CN105315574A (en) * | 2015-10-12 | 2016-02-10 | 浙江工业大学 | Calcium and zinc heat stabilizer for PVC and application of calcium and zinc heat stabilizer |
| CN106084294A (en) * | 2016-06-20 | 2016-11-09 | 河南师范大学 | A kind of beta diketone class organotin PVC heat stabilizer and preparation method thereof |
| CN106117263A (en) * | 2016-06-25 | 2016-11-16 | 安徽升华新奥特化工有限公司 | A kind of Methyl stannum mercaptide stabilizer of environmental protection |
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