CN106431916A - Preparation method of compound - Google Patents
Preparation method of compound Download PDFInfo
- Publication number
- CN106431916A CN106431916A CN201610723343.XA CN201610723343A CN106431916A CN 106431916 A CN106431916 A CN 106431916A CN 201610723343 A CN201610723343 A CN 201610723343A CN 106431916 A CN106431916 A CN 106431916A
- Authority
- CN
- China
- Prior art keywords
- formula
- preparation
- compound
- compound shown
- carbonate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of a compound shown in the formula (I). The method is characterized by including the following steps of firstly, mixing the compound shown in the formula (I), a compound shown in the formula (III), strong alkali and weak acid salt and a catalyst to obtain a mixed solution; secondly, conducting heating and refluxing on the mixed solution obtained in the first step, and conducting post-processing to obtain the compound shown in the formula (I), wherein X is Cl, Br or I. The method can effectively improve the yield and safety of the compound shown in the formula (I). Please see the formula in the description.
Description
Technical field
The present invention relates to plant growth regulator synthesis field is and in particular to a kind of preparation method of compound.
Background technology
Increasingly it is widely applied with plant growth regulator, the research and development of plant growth regulator, it has also become plant gives birth to
One of main development direction of long conditioning agent industry.The plant growth regulator occurring on the market is varied, wherein, ring propionyl
Amino acid (common name Cyclanilide, trade name Finish) is the important plant growth regulator containing cyclopropane moiety of a class.
With ethephon (CEPHA),2-(chloroethyl) phosphonic acid, there is synergistic function, be mainly used in the crops such as cotton.
At present, the method for synthesis ring malonamic acid is, from dichloroethanes, compound and potassium carbonate shown in formula (II),
Dimethylformamide or dimethylacetylamide as compound shown in synthesis formula (I) under solvent action, compound shown in formula (I) with
After the aminolysis reaction that ester occurs, hydrolysis obtains ring malonamic acid to 2,4- dichloroanilines, compound shown in intermediate product formula (I)
Building-up process, synthetic yield not high thus affecting the yield of ring malonamic acid.Meanwhile, the dimethylformamide as solvent and two
Methylacetamide belongs to medium low noxious material, can invade internal through respiratory tract, skin and alimentary canal, big to harm.
Content of the invention
The technical problem to be solved in the present invention is, provides the preparation method of compound shown in a kind of formula (I), methods described
The yield of compound and security shown in preparation formula (I) can be improved.
In order to solve above technical problem, the invention provides the preparation method of compound shown in a kind of formula (I), its feature
It is, comprise the following steps：
1) compound shown in formula (II), compound, strong base-weak acid salt shown in formula (III) are mixed with catalyst, mixed
Close solution；
2) by described step 1) the described mixed solution that obtains is heated to reflux, post-treated compound shown in formula (I)；
Described X is Cl, Br or I.
Preferably, described step 1) in by compound shown in described formula (II), compound shown in described formula (III), described
Strong base-weak acid salt and described catalyst molar ratio are 1:(2.2～3.5)：(1～2)：(0.005～0.02).
Preferably, described mol ratio is 1:(2.2～3.5)：(1～2)：(0.005～0.01).
Preferably, described mol ratio is 1:(2.2～3.5)：(1～2)：0.01.
Preferably, described step 1) described in strong base-weak acid salt be carbonate or bicarbonate.
Preferably, described step 1) described in strong base-weak acid salt be carbonate.Preferably, described carbonate be sodium carbonate,
One or more in potassium carbonate, magnesium carbonate or calcium carbonate；Described bicarbonate be sodium acid carbonate, saleratus, magnesium bicarbonate or
One or more in calcium carbonate.
Preferably, described carbonate is sodium carbonate or potassium carbonate.
Preferably, described bicarbonate is sodium acid carbonate, saleratus.
Preferably, described step 1) described in catalyst be TBAB.
Preferably, described step 2) described in be heated to reflux equipment therefor and include reaction bulb, titration funnel and condenser pipe；Institute
State titration funnel lower end to be connected with described reaction bulb, described titration funnel upper end is connected with described condenser pipe.
Preferably, described step 2) described in post-process for fractionation.
Preferably, described step 2) described in post-process for distillation, extraction, washing, be dried, filter.
Preferably, described step 2) described in post-process for vacuum distillation, ether extraction, washing, anhydrous slufuric acid ammonium be dried,
Filter, concentrate.
Preferably, described step 2) described in heating-up temperature be 100～150 DEG C.
Preferably, described step 2) described in heating-up temperature be 110～140 DEG C.
Preferably, described step 2) described in heating-up temperature be 120 DEG C.
Compared with prior art, its detailed description is as follows for the present invention：
The described preparation method that the present invention provides adopts compound shown in described formula (II), chemical combination shown in described formula (III)
Thing, described strong base-weak acid salt and described catalyst are with mol ratio 1:(2.2～3.5)：(1～2)：(0.005～0.02) is mixed into
Row reaction, reasonable mixture ratio, reaction yield is high.The process that reaction obtains the described compound of described formula (I) can produce accessory substance, described
Accessory substance is water, and the described described compound of formula (III) and described water byproduct enter cold in described condenser pipe in the form of a vapor
Coagulate for liquid, be back in described constant voltage titration funnel, and the described compound of formula (III) density is big compared with water, and formula (III)
Described compound is immiscible with water, and therefore described constant voltage titration funnel lower floor is the described compound of described formula (III), and upper strata is institute
State water byproduct, the described compound of described formula (III) titrates funnel by described constant voltage and returns in described reaction bulb, described pair
Product water is stayed in constant voltage titration funnel, is conducive to improving the described compound yield of described formula (I).Meanwhile, the present invention selects four
Butylammonium bromide makees catalyst, is not required to be reacted using toxic solvent, improves reaction safety.
Brief description
In order to be illustrated more clearly that the embodiment of the present invention or technical scheme of the prior art, below will be to institute in embodiment
Need use accompanying drawing be briefly described it should be apparent that, drawings in the following description be only the present invention some enforcement
Example, for those of ordinary skill in the art, on the premise of not paying creative work, can also obtain according to these accompanying drawings
Obtain other accompanying drawings.
Fig. 1 is heated to reflux equipment therefor schematic diagram for of the present invention.
Specific embodiment
In order that those skilled in the art more fully understands technical scheme, with reference to specific embodiment pair
The present invention is described in further detail.
The technical problem to be solved in the present invention is, provides the preparation method of compound shown in a kind of formula (I), methods described
The yield of compound and security shown in preparation formula (I) can be improved.
In order to solve above technical problem, the present invention provides the invention provides the preparation of compound shown in a kind of formula (I)
Method is it is characterised in that comprise the following steps：
1) compound shown in formula (II), compound, strong base-weak acid salt shown in formula (III) are mixed with catalyst, mixed
Close solution；
2) by described step 1) the described mixed solution that obtains is heated to reflux, post-treated compound shown in formula (I)；
Described X is Cl, Br or I.
Step 1 of the present invention) in by compound shown in described formula (II), compound shown in described formula (III), described strong
Alkali salt of weak acid and described catalyst molar ratio are 1:(2.2～3.5)：(1～2)：(0.005～0.02)；Preferably 1:(2.2
～2.5)：(1.4～1.8)：(0.005～0.2)；More preferably 1:(2.2～2.5)：(1.4～1.8)：0.01.Described step
Strong base-weak acid salt described in rapid 1) is preferably carbonate or bicarbonate；Be more highly preferred to for described bicarbonate；Described carbon
Hydrochlorate is sodium carbonate, potassium carbonate, one or more in magnesium carbonate or calcium carbonate；Described bicarbonate is sodium acid carbonate, bicarbonate
One or more in potassium, magnesium bicarbonate or calcium carbonate.Described catalyst is preferably TBAB.
Step 2 of the present invention) described in be heated to reflux equipment therefor and include reaction bulb, titration funnel and condenser pipe；Institute
State titration funnel lower end to be connected with described reaction bulb, described titration funnel upper end is connected with described condenser pipe.Described titration funnel
It is preferably constant voltage titration funnel.Described step 2) described in post-process for fractionation；Preferably, described post-process for distillation, extraction,
Washing, dry, filtration；Be more highly preferred to is dried, filters, concentrates for vacuum distillation, ether extraction, washing, anhydrous slufuric acid ammonium.Institute
State preferably 100～150 DEG C of heating-up temperature；Be more highly preferred to for 110～140 DEG C；Highly preferred is 120 DEG C
Embodiment 1～25
Weigh compound shown in described formula (II), compound, potassium carbonate shown in described formula (III) as table 1, with tetrabutyl bromine
Change ammonium 0.1mol, described X is Cl, mixing；Add to being heated to reflux shown in Fig. 1 in device, reaction bulb is connected with constant voltage titration leakage
Bucket, constant voltage titration funnel upper end is connected with condenser pipe, stirring, and is heated to flowing back, and 120 DEG C of isothermal reactions 2.5～6 hours make
After the liquid that reaction is obtained filters, after being washed with frozen water in separatory funnel, stratification, the organic phase of lower floor is put into cone
Vacuum distillation in shape bottle；The distillation of acquisition is poured in frozen water, with ether extraction, washs ether layer；Anhydrous slufuric acid ammonium is dried,
Filter, concentrate, obtain compound shown in formula (I) and calculate yield, the results are shown in Table 1.
Table 1
Embodiment 31
Weigh compound 1mol shown in described formula (II), compound 3.5mol and tetrabutyl phosphonium bromide shown in described formula (III)
Ammonium 0.1mol, described X are Cl, and weigh potassium carbonate by table 4, mixing；Add to being heated to reflux shown in Fig. 1 in device, reaction bulb
It is connected with constant voltage titration funnel, constant voltage titration funnel upper end is connected with condenser pipe, stirring, and is heated to flowing back, and 120 DEG C of constant temperature are anti-
Answer 6 hours, after the liquid that reaction is obtained filters, after being washed with frozen water in separatory funnel, stratification, lower floor is organic
Mutually put into vacuum distillation in conical flask；The distillation of acquisition is poured in frozen water, with ether extraction, washs ether layer；Anhydrous sulphur
Sour ammonium drying, filters, concentrates, obtain compound shown in formula (I), records shown in described formula (II) that remain after reacting and hydrolysis
Compound quality, calculates compound production shown in formula (I), the results are shown in Table 2.
Table 2
| Test number | Experimental group 1 | Experimental group 2 | Experimental group 3 | Experimental group 4 | Experimental group 5 |
| Test the mole (mol) of the middle potassium carbonate that feeds intake | 1 | 1.2 | 1.4 | 1.6 | 1.8 |
| The compound quality (g) shown in formula (II) of residual | 7.53 | 5.94 | 4.07 | 3.18 | 0 |
| The compound quality (g) shown in formula (II) being hydrolyzed | 8.58 | 7.93 | 6.81 | 6.44 | 6.31 |
| Compound yield (%) shown in formula (I) | 46.30 | 53.76 | 63.76 | 74.59 | 82.50 |
Obtained by above-mentioned, the compound shown in middle formula (II) that feeds intake, the mol ratio of compound shown in formula (III) are 1:3.5, with
The increase of carbonic acid potassium application rate, its mole rises to 1.8 moles from 1 mole, feed intake what compound shown in middle formula (II) was hydrolyzed
Amount occurs gradually decreasing trend, the compound shown in middle formula (II) that makes to feed intake be converted into compound shown in formula (I) amount more so that
The yield of compound shown in formula (I) increases.
Embodiment 32～embodiment 35
Weigh compound 1mol shown in described formula (II), compound 2.5mol and potassium carbonate shown in described formula (III)
1.8mol, weighs TBAB by table 3, and described X is Cl, mixing；Add to being heated to reflux shown in Fig. 1 in device, react
Bottle is connected with constant voltage titration funnel, and constant voltage titration funnel upper end is connected with condenser pipe, stirring, and is heated to flowing back, 120 DEG C of constant temperature
Reaction 3 hours, after the liquid that reaction is obtained filters, after being washed with frozen water in separatory funnel, stratification, having lower floor
Machine phase puts into vacuum distillation in conical flask；The distillation of acquisition is poured in frozen water, with ether extraction, washs ether layer；Anhydrous
Ammonium sulfate is dried, and filters, and concentrates, obtains compound shown in formula (I) and calculate compound production shown in formula (I), the results are shown in Table 3.
Table 3
Can be obtained by table 1～5, strong base-weak acid salt described in compound shown in compound, described formula (II) shown in described formula (I) with
Described catalyst molar ratio is 1:(2.2～3.5)：(1～2)：(0.005～1), reaction yield is higher, yield be 45.32%～
83.47%, preferably 1:(2.2～2.5)：(1.4～1.8)：(0.005～0.1) yield is 53.93%～83.47%.
Embodiment 36～embodiment 45
Weigh compound 30g shown in formula (II), TBAB 0.6g, and weigh compound shown in formula (III) as table 3
With described strong base-weak acid salt, compound shown in described formula (I), compound, described strong base-weak acid salt and four shown in described formula (II)
Butylammonium bromide that ratio is 1：2.5：1.8, mixing, add to being heated to reflux shown in Fig. 1 in device, reaction bulb is connected with constant voltage and drips
Determine funnel, constant voltage titration funnel upper end is connected with condenser pipe, stirring, and is heated to flowing back, isothermal reaction, the liquid that reaction is obtained
After body filters, after being washed with frozen water in separatory funnel, stratification, the organic phase of lower floor is put into decompression in conical flask and steams
Evaporate；The distillation of acquisition is poured in frozen water, with ether extraction, washs ether layer；Anhydrous slufuric acid ammonium is dried, and filters, and concentrates, obtains
To compound shown in formula (I) and calculate yield, reaction temperature, time and yield are shown in Table 4.
Table 4
Embodiment 46～embodiment 58
Weigh compound 30g shown in formula (II), compound 80.94g, sodium carbonate 35.74g and the tetrabutyl shown in formula (III)
Ammonium bromide 0.6g, described X are Br, and mixing adds to being heated to reflux shown in Fig. 1 in device, and reaction bulb is connected with constant voltage titration leakage
Bucket, constant voltage titration funnel upper end is connected with condenser pipe, stirring, and is heated to flowing back, isothermal reaction, the liquid mistake that reaction is obtained
After filter, after being washed with frozen water in separatory funnel, stratification, the organic phase of lower floor is put into vacuum distillation in conical flask；Will
The distillation obtaining is poured in frozen water, with ether extraction, washs ether layer；Anhydrous slufuric acid ammonium is dried, and filters, and concentrates, obtains formula
(I) compound shown in simultaneously calculates yield, and reaction temperature, time and yield are shown in Table 5.
Table 5
Obtained by above-mentioned, when temperature of the present invention is preferably 100～150 DEG C, reaction yield is higher, more preferably 110～140
DEG C, optimum is 120 DEG C, and the simultaneous reactions time is preferably 3～6h.
The above is only the preferred embodiment of the present invention it is noted that above-mentioned preferred embodiment be not construed as right
The restriction of the present invention, protection scope of the present invention should be defined by claim limited range.For the art
For those of ordinary skill, without departing from the spirit and scope of the present invention, some improvements and modifications can also be made, these change
Enter and retouch also to should be regarded as protection scope of the present invention.
Claims (10)
1. the preparation method of compound shown in a kind of formula (I) is it is characterised in that comprise the following steps：
1) compound shown in formula (II), compound, strong base-weak acid salt shown in formula (III) are mixed with catalyst, obtain mixing molten
Liquid；
2) by described step 1) the described mixed solution that obtains is heated to reflux, post-treated compound shown in formula (I)；
Described X is Cl, Br or I.
2. preparation method according to claim 1 is it is characterised in that described step 1) in by chemical combination shown in described formula (II)
Thing, compound shown in described formula (III), described strong base-weak acid salt and described catalyst molar ratio are 1:(2.2～3.5)：(1～
2)：(0.005～0.02).
3. preparation method according to claim 2 is it is characterised in that described step 1) in by chemical combination shown in described formula (II)
Thing, compound shown in described formula (III), described strong base-weak acid salt and described catalyst molar ratio are 1:(2.2～2.5)：(1～
2)：(0.005～0.01).
4. preparation method according to claim 1 is it is characterised in that described step 1) described in strong base-weak acid salt be carbonic acid
Salt or bicarbonate.
5. preparation method according to claim 4 it is characterised in that described carbonate be sodium carbonate, potassium carbonate, magnesium carbonate
Or one or more in calcium carbonate；Described bicarbonate is sodium acid carbonate, saleratus, in magnesium bicarbonate or calcium carbonate a kind of or
Multiple.
6. preparation method according to claim 1 is it is characterised in that described step 1) described in catalyst be tetrabutyl bromine
Change ammonium.
7. preparation method according to claim 1 is it is characterised in that described step 2) described in be heated to reflux equipment therefor
Including reaction bulb, titration funnel and condenser pipe；Described titration funnel lower end is connected with described reaction bulb, described titration funnel upper end
It is connected with described condenser pipe.
8. preparation method according to claim 1 is it is characterised in that described step 2) described in post-process as distillation, extraction
Take, wash, be dried, filter.
9. preparation method according to claim 1 is it is characterised in that described step 2) described in heating-up temperature be 100～
150℃.
10. preparation method according to claim 9 is it is characterised in that described step 2) described in heating-up temperature be 110～
140℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610723343.XA CN106431916A (en) | 2016-08-25 | 2016-08-25 | Preparation method of compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610723343.XA CN106431916A (en) | 2016-08-25 | 2016-08-25 | Preparation method of compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106431916A true CN106431916A (en) | 2017-02-22 |
Family
ID=58181923
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610723343.XA Pending CN106431916A (en) | 2016-08-25 | 2016-08-25 | Preparation method of compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106431916A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109232246A (en) * | 2018-10-30 | 2019-01-18 | 上海应用技术大学 | A kind of synthesis technology of 3- methyl-cyclobutyl -1,1- diethyl dicarboxylate |
| CN114988999A (en) * | 2021-11-17 | 2022-09-02 | 郑州尼采生物科技有限公司 | 1-formamido-1-cyclopropane carboxylic acid compound and synthesis method and application of derivative thereof |
-
2016
- 2016-08-25 CN CN201610723343.XA patent/CN106431916A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| XIAO-WEI CHANG ET AL: "1-Aminoxymethylcyclopropanecarboxylic acid as building block of β N-O turn and helix: synthesis and conformational analysis in solution and in the solid state", 《TETRAHEDRON》 * |
| 任旭康等: "5-溴乙基海因", 《农药》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109232246A (en) * | 2018-10-30 | 2019-01-18 | 上海应用技术大学 | A kind of synthesis technology of 3- methyl-cyclobutyl -1,1- diethyl dicarboxylate |
| CN114988999A (en) * | 2021-11-17 | 2022-09-02 | 郑州尼采生物科技有限公司 | 1-formamido-1-cyclopropane carboxylic acid compound and synthesis method and application of derivative thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105921161B (en) | A kind of catalyst and preparation method thereof preparing 2,5- chlorophenesic acids for paracide hydroxylating | |
| CN104151152B (en) | A kind of three circulating methods preparing phenoxy acetic acid without waste water | |
| CN106431916A (en) | Preparation method of compound | |
| CN107118069A (en) | A kind of method that utilization isobutyl dehydration of alcohols prepares isobutene | |
| CN108129393A (en) | A kind of method of by-product and solvent recycled in metronidazole production | |
| CN109608361A (en) | A kind of synthetic method of two chloroacetonitriles | |
| CN103483165B (en) | Prepare the green cleaning procedure of ortho-formiate | |
| CN106278964A (en) | The preparation method of florfenicol | |
| CN109438409A (en) | A kind of method of synthesizing annular carbonate | |
| CN203853071U (en) | Reaction kettle for synthesizing carbamates compound by urea method | |
| CN104829509A (en) | Preparation method of rubber vulcanization accelerator | |
| CN104478747B (en) | A kind of method utilizing organic solvent to produce glycine | |
| CN109096206A (en) | A kind of method of acidity photocatalytic method synthesis carbendazim | |
| CN101531831B (en) | Production method of direct blended brown D-RS dye | |
| CN202705267U (en) | Glycol dimethyl ether component recovery device in synthetic product waste salt | |
| CN102491910B (en) | Method for synthesizing 2,6-dibromo-4-(trifluoromethoxy) aniline by water-phase method | |
| CN106431833B (en) | A kind of technique for preparing the terephthalyl alcohol of 2,3,5,6 tetrafluoro 1,4 | |
| CN105218474A (en) | The synthetic method of (4R, 5R)-2-dichloromethyl-4,5-dihydro-5-(4-methylsulfonyl phenyl)-4-oxazole methyl alcohol | |
| CN110527098A (en) | The post-processing approach and polysiloxanes of polysiloxanes synthesis | |
| CN206494875U (en) | One kind 4,4 ' di-2-ethylhexylphosphine oxides of production（The chloroaniline of 2,6 diethyl 3）Equipment | |
| CN107245043B (en) | A kind of preparation method preparing 3 methylthiol propyl alcohol from 3- methylthiopropionaldehydes | |
| CN210595858U (en) | Production device for reducing dioxin in tetrachlorobenzoquinone preparation | |
| CN108499592A (en) | One kind being used for CO2Catalyst of cycloaddition reaction and preparation method thereof | |
| CN204170712U (en) | A kind of for the epoxidised tubular reaction device of unsaturated fatty acid ester | |
| CN109836364A (en) | The method of pipeline continuous production aryl disulfide compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170222 |
|
| RJ01 | Rejection of invention patent application after publication |