CN110862310B - Synthesis method of cyclopropyl methyl ketone - Google Patents
Synthesis method of cyclopropyl methyl ketone Download PDFInfo
- Publication number
- CN110862310B CN110862310B CN201911235730.9A CN201911235730A CN110862310B CN 110862310 B CN110862310 B CN 110862310B CN 201911235730 A CN201911235730 A CN 201911235730A CN 110862310 B CN110862310 B CN 110862310B
- Authority
- CN
- China
- Prior art keywords
- methyl ketone
- cyclopropyl methyl
- reaction
- chloro
- pentanone
- 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.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
- C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
- C07C45/59—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Abstract
The invention relates to a synthesis method of cyclopropyl methyl ketone, which comprises the following steps: 1) Carrying out hydro-hydrolysis on 2-methylfuran by adopting a one-pot method in the presence of a hydrogenation catalyst, hydrogen and water to prepare acetyl-n-propanol; 2) Performing hydrochloric acid chlorination reaction on the acetyl-n-propanol prepared in the step 1) to prepare 5-chloro-2-pentanone; 3) Performing a ring closing reaction on the crude product of the 5-chloro-2-pentanone prepared in the step 2) under an alkaline condition to obtain the cyclopropyl methyl ketone. The synthesis method of the cyclopropyl methyl ketone takes 2-methylfuran as a raw material, and the cyclopropyl methyl ketone is prepared through one-pot hydrogenation hydrolysis, hydrochloric acid chlorination reaction and ring closing reaction, so that the process is simple and smooth, the reaction condition is mild, and the method is suitable for industrial amplification production; 2-methylfuran is adopted as a raw material, so that the atom economy is high, the environment is protected, and the raw material cost is low.
Description
Technical Field
The invention relates to the field of chemical synthesis, in particular to a synthetic method of cyclopropyl methyl ketone.
Background
Cyclopropyl methyl ketone is an important raw material of the bactericide cyproconazole, and the problems of complex process, high raw material cost, high difficulty in industrial amplification production and the like exist in the existing synthesis process. 5-chloro-2-pentanone or acetylbutyrolactone used as a raw material as reported in patents CN200610098154 and CN201210099170 has high raw material cost and low economic benefit; the 2-methyl furan obtained by hydrogenating 2-methyl furan reported in patent CN201611008606 is re-isomerized into cyclopropyl methyl ketone, the catalyst is expensive, the yield is too low, and the raw material cost is high; as reported in patent CN201511010127, the method for preparing cyclopropyl methyl ketone by cracking acetyl butyrolactone at high temperature has high cost of raw material, solvent and catalyst, and harsh conditions, and is not suitable for industrialization.
Therefore, the problem to be solved by the technical personnel in the field is to find a synthesis process of cyclopropyl methyl ketone, which has simple and smooth process, low cost and suitable industrialized scale-up production.
Disclosure of Invention
The invention provides a synthesis method of cyclopropyl methyl ketone, aiming at solving the problems of complex process, high raw material cost, high difficulty in industrial amplification production and the like in the existing synthesis process of cyclopropyl methyl ketone.
In order to realize the purpose, the invention adopts the following technical scheme:
the invention provides a synthesis method of cyclopropyl methyl ketone, which comprises the following steps:
(1) Carrying out hydro-hydrolysis on 2-methylfuran by adopting a one-pot method in the presence of a hydrogenation catalyst, hydrogen and water to prepare acetyl-n-propanol;
(2) Performing hydrochloric acid chlorination reaction on the acetyl-n-propanol prepared in the step (1) to prepare 5-chloro-2-pentanone;
(3) And (3) carrying out ring closing reaction on the crude product of the 5-chloro-2-pentanone prepared in the step (2) under an alkaline condition to obtain the cyclopropyl methyl ketone.
Further, in the step (1), the hydrogenation catalyst is a metal catalyst containing palladium, platinum or nickel.
Further preferably, the metal catalyst is a palladium carbon catalyst, wherein the mass percent of palladium is 1-50wt%.
Further preferably, the mass percentage of palladium in the palladium on carbon catalyst is 5 to 10wt%.
Further, in the step (1), the temperature of the hydrogenation hydrolysis is 0-50 ℃, the pressure is 0.01-0.4MPa, and the hydrogenation time is 1-5h.
Further preferably, in the step (1), the temperature of the hydrogenation hydrolysis is 20-30 ℃, the pressure is 0.1-0.3MPa, and the hydrogenation time is 2-3h.
Further, in the step (1), the mass ratio of the hydrogenation catalyst, the 2-methylfuran and the water is 1 (50-3000) to (50-3000).
Further preferably, the mass ratio of the hydrogenation catalyst, the 2-methylfuran and the water is 1 (50-1000) to (50-1000).
Further, the step (2) is specifically: and dropwise adding the obtained acetyl-n-propanol into heated hydrochloric acid, performing azeotropic distillation while dropwise adding to obtain a product 5-chloro-2-pentanone, and standing for layering to obtain a crude product 5-chloro-2-pentanone.
Further preferably, the solubility of the hydrochloric acid is 10% -30%, and the heating temperature is 80-100 ℃.
Further preferably, the solubility of the hydrochloric acid is 15% -20%, and the heating temperature is 90-95 ℃.
Further preferably, the molar ratio of acetyl-n-propanol to hydrochloric acid is 1.5-4.0.
Further preferably, the molar ratio of acetyl n-propanol to hydrochloric acid is 1.
Further, in the step (3), the alkali used in the alkaline condition is sodium hydroxide, potassium hydroxide or calcium hydroxide, and the concentration of the alkali is 5-30%.
Further preferably, the concentration of the base is 15-20%.
Further preferably, the base is sodium hydroxide.
Further, in the step (3), the temperature of the ring closing reaction is 50-100 ℃, and the reaction time is 1-5h; the molar ratio of the 5-chloro-2-pentanone to the base is 1.01-3.0.
Further preferably, the temperature of the ring closing reaction is 70-80 ℃, and the reaction time is 2h; the molar ratio of the 5-chloro-2-pentanone to the base is 1.5-2.0.
By adopting the technical scheme, compared with the prior art, the invention has the following technical effects:
the synthesis method of the cyclopropyl methyl ketone takes 2-methylfuran as a raw material, and the cyclopropyl methyl ketone is prepared through one-pot hydrogenation hydrolysis, hydrochloric acid chlorination reaction and ring closing reaction, so that the process is simple and smooth, the reaction condition is mild, and the method is suitable for industrial amplification production; 2-methylfuran is adopted as a raw material, so that the atom economy is high, the environment is protected, and the raw material cost is low.
Drawings
FIG. 1 is a scheme showing the synthesis of cyclopropyl methyl ketone according to the present invention.
Detailed Description
The present invention will now be described in detail and specifically by the following examples to provide a better understanding of the present invention, but the following examples are not intended to limit the scope of the present invention.
Example 1
Synthesis of cyclopropyl methyl ketone: adding 400g of 2-methylfuran, 100g of water and 2g of 5% palladium-carbon catalyst into a 1000ml hydrogenation kettle, replacing with hydrogen after nitrogen replacement, stirring to control the reaction temperature to be 28 ℃, continuously hydrogenating with a hydrogen balloon, finishing after 3 hours of reaction, filtering reaction liquid after nitrogen replacement, mechanically using the catalyst for the next batch, standing and layering the reaction liquid, and mechanically using a water layer for the next batch; the organic phase, i.e., n-propanol, was 448g, 95.3% pure.
340g of 20% hydrochloric acid was added to a 1000ml three-necked flask, and heated to 90 ℃ to add 100g of the above acetyl-n-propanol dropwise while collecting 5-chloro-2-pentanone and dilute acid water as an azeotrope by distillation. After the dropwise addition is finished, continuously distilling until no organic phase is evaporated, and standing and layering to obtain 130g of crude 5-chloro-2-pentanone with the purity of 96.1% as an organic phase; the aqueous layer can be used for the next batch of chlorination reaction.
Adding 100g of the 5-chloro-2-pentanone and 318g of 20% sodium hydroxide into a 1000ml three-necked bottle, stirring and heating to 75 ℃, reacting for 2 hours, standing and layering to obtain 65g of cyclopropyl methyl ketone as an organic phase, 1 HNMR(400MHz,CDCl 3 ) δ 2.08 (s, 3H), 1.98 (m, 1H), 0.81-0.56 (m, 4H), purity 97.5%.
Example 2
Synthesis of cyclopropyl methyl ketone: adding 400g of 2-methylfuran, 100g of water and 2g of 10% palladium-carbon catalyst into a 1000ml hydrogenation kettle, replacing with nitrogen, replacing with hydrogen, stirring to control the reaction temperature to be 30 ℃, continuously hydrogenating with a hydrogen balloon, finishing the reaction after 2.5 hours, filtering the reaction solution after replacing with nitrogen, mechanically applying the catalyst to the next batch, standing and layering the reaction solution, and mechanically applying the water layer to the next batch; the organic phase, i.e., n-propanol, 448g had a purity of 95.5%.
In a 1000ml three-necked flask, 340g of 15% hydrochloric acid was added, heated to 92 ℃ and 100g of the above acetyl-n-propanol was added dropwise while collecting 5-chloro-2-pentanone and dilute acid water as azeotropes by distillation. After the dropwise addition is finished, continuously distilling until no organic phase is evaporated, standing and layering to obtain 130g of 5-chloro-2-pentanone with the purity of 96.2% from the organic phase; the aqueous layer can be used for the next batch of chlorination reaction.
And (2) adding 100g of 5-chloro-2-pentanone and 318g of 20% sodium hydroxide into a 1000ml three-neck bottle, stirring and heating to 70 ℃, reacting for 2 hours, standing and layering to obtain 65g of cyclopropyl methyl ketone with the purity of 97.4% as an organic phase.
Example 3
Synthesis of cyclopropyl methyl ketone: adding 400g of 2-methylfuran, 100g of water and 2g of 10% palladium-carbon catalyst into a 1000ml hydrogenation kettle, replacing with hydrogen after nitrogen replacement, stirring to control the reaction temperature to be 25 ℃, continuously hydrogenating with a hydrogen balloon, finishing after 2 hours of reaction, filtering reaction liquid after nitrogen replacement, mechanically applying the catalyst to the next batch, standing and layering the reaction liquid, and mechanically applying the water layer to the next batch; the organic phase, i.e., n-propanol, 448g had a purity of 95.2%.
340g of 20% hydrochloric acid was added to a 1000ml three-necked flask, heated to 95 ℃ and 100g of the above acetyl-n-propanol was added dropwise while collecting 5-chloro-2-pentanone and dilute acid water as an azeotrope by distillation. After the dropwise adding is finished, continuously distilling until no organic phase is distilled out, standing and layering to obtain 130g of 5-chloro-2-pentanone with the purity of 96%; the aqueous layer was used for the next batch of chlorination.
And (3) adding 100g of the 5-chloro-2-pentanone and 318g of 20% sodium hydroxide into a 1000ml three-necked bottle, stirring and heating to 80 ℃, reacting for 2 hours, and standing for layering to obtain 65g of cyclopropyl methyl ketone with the purity of 97.1% as an organic phase.
The embodiments of the present invention have been described in detail, but the embodiments are merely examples, and the present invention is not limited to the embodiments described above. Any equivalent modifications and substitutions to those skilled in the art are also within the scope of the present invention. Accordingly, equivalent changes and modifications made without departing from the spirit and scope of the present invention should be covered by the present invention.
Claims (11)
1. A synthesis method of cyclopropyl methyl ketone is characterized by comprising the following steps:
(1) Carrying out hydro-hydrolysis on 2-methylfuran by adopting a one-pot method in the presence of a hydrogenation catalyst, hydrogen and water to prepare acetyl-n-propanol;
(2) Performing hydrochloric acid chlorination reaction on the acetyl-n-propanol prepared in the step (1) to prepare 5-chloro-2-pentanone;
(3) Performing a ring closing reaction on the crude product of the 5-chloro-2-pentanone prepared in the step (2) under an alkaline condition to obtain cyclopropyl methyl ketone;
in the step (1), adding 2-methylfuran, water and a hydrogenation catalyst into a hydrogenation kettle, replacing with hydrogen after nitrogen replacement, stirring to control the reaction temperature, continuously performing hydrogenation reaction by using a hydrogen balloon, filtering reaction liquid after nitrogen replacement, standing and layering the reaction liquid, wherein an organic phase is acetyl-n-propanol; wherein the hydrogenation catalyst is a palladium carbon catalyst, and the mass percent of palladium in the palladium carbon catalyst is 5-10wt%; the temperature of the hydrogenation hydrolysis is 20-30 ℃, the pressure is 0.1-0.3MPa, and the hydrogenation time is 2-3h; the mass ratio of the hydrogenation catalyst, the 2-methylfuran and the water is 1 (50-1000) to 50-1000.
2. The synthesis method of cyclopropyl methyl ketone according to claim 1, wherein the step (2) is specifically: and dropwise adding the obtained acetyl-n-propanol into heated hydrochloric acid, performing azeotropic distillation while dropwise adding to obtain a product 5-chloro-2-pentanone, and standing for layering to obtain a crude product 5-chloro-2-pentanone.
3. The synthesis method of cyclopropyl methyl ketone according to claim 2, wherein the mass concentration of the hydrochloric acid is 10% -30%, and the heating temperature is 80-100 ℃.
4. The synthesis method of cyclopropyl methyl ketone according to claim 3, wherein the mass concentration of the hydrochloric acid is 15% -20%, and the heating temperature is 90-95 ℃.
5. The method for synthesizing cyclopropyl methyl ketone according to claim 2, wherein the molar ratio of acetyl n-propanol to hydrochloric acid is 1.5 to 4.0.
6. The method for synthesizing cyclopropyl methyl ketone according to claim 5, wherein the molar ratio of acetyl n-propanol to hydrochloric acid is 1.
7. The method for synthesizing cyclopropyl methyl ketone according to claim 1, wherein in step (3), the alkali used in the alkaline condition is sodium hydroxide, potassium hydroxide or calcium hydroxide, and the concentration thereof is 5-30%.
8. The method of claim 7, wherein the concentration of the base is 15-20%.
9. The method for synthesizing cyclopropyl methyl ketone according to claim 7, wherein the base is sodium hydroxide.
10. The synthesis method of cyclopropyl methyl ketone according to claim 1, wherein in step (3), the temperature of the ring closure reaction is 50-100 ℃, and the reaction time is 1-5h; the molar ratio of the 5-chloro-2-pentanone to the base is 1.01-3.0.
11. The synthesis method of cyclopropyl methyl ketone according to claim 10, wherein the temperature of the ring closing reaction is 70-80 ℃, and the reaction time is 2h; the molar ratio of the 5-chloro-2-pentanone to the base is 1.5-2.0.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911235730.9A CN110862310B (en) | 2019-12-05 | 2019-12-05 | Synthesis method of cyclopropyl methyl ketone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911235730.9A CN110862310B (en) | 2019-12-05 | 2019-12-05 | Synthesis method of cyclopropyl methyl ketone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110862310A CN110862310A (en) | 2020-03-06 |
| CN110862310B true CN110862310B (en) | 2022-12-27 |
Family
ID=69657780
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911235730.9A Active CN110862310B (en) | 2019-12-05 | 2019-12-05 | Synthesis method of cyclopropyl methyl ketone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110862310B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112717988B (en) * | 2021-02-07 | 2022-06-24 | 郑州大学 | Efficient pollution-free catalyst for preparing acetyl-n-propanol and preparation method and use method thereof |
| CN113072434B (en) * | 2021-04-01 | 2023-09-12 | 上海创诺医药集团有限公司 | Method for preparing cyclopropyl methyl ketone by one-step method |
| CN113582824B (en) * | 2021-08-26 | 2024-01-30 | 江苏清泉化学股份有限公司 | Preparation method of high-purity cyclopropyl methyl ketone |
| CN113816841A (en) * | 2021-10-12 | 2021-12-21 | 瑞孚信江苏药业股份有限公司 | Preparation method of cyclopropyl methyl ketone |
| CN115850039B (en) * | 2022-12-01 | 2024-01-02 | 江苏中旗科技股份有限公司 | Method for synthesizing cyclopropylmethyl ketone through imine intermediate |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106966879A (en) * | 2017-02-20 | 2017-07-21 | 山东诺生物质材料有限公司 | A kind of autoclave continuously hydrogen adding produces the equipment and technique of acetyl normal propyl alcohol |
| CN110052049A (en) * | 2019-05-24 | 2019-07-26 | 山东一诺生物质材料有限公司 | The device and method of 2- methylfuran continuously hydrogen adding production acetyl normal propyl alcohol |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100494146C (en) * | 2006-12-05 | 2009-06-03 | 安徽绩溪县徽煌化工有限公司 | Process for preparing cyclopropyl methyl ketone |
| CN102140058B (en) * | 2011-02-26 | 2013-08-21 | 安徽绩溪县徽煌化工有限公司 | Method for preparing gamma-acetyl propanol |
| CN102643179A (en) * | 2012-04-07 | 2012-08-22 | 安徽绩溪县徽煌化工有限公司 | Preparation method of cyclopropyl methyl ketone |
| CN103694094B (en) * | 2013-11-11 | 2016-08-17 | 江苏清泉化学股份有限公司 | A kind of preparation method of the chloro-2 pentanone of 5- |
| CN106554263B (en) * | 2016-11-16 | 2019-11-08 | 江苏清泉化学股份有限公司 | A kind of preparation method of cyclopropyl methyl ketone |
| CN109748783A (en) * | 2019-01-31 | 2019-05-14 | 河北诚信集团有限公司 | A kind of preparation method of the chloro- 1- of 2- (1- chlorine cyclopropyl) ethyl ketone |
-
2019
- 2019-12-05 CN CN201911235730.9A patent/CN110862310B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106966879A (en) * | 2017-02-20 | 2017-07-21 | 山东诺生物质材料有限公司 | A kind of autoclave continuously hydrogen adding produces the equipment and technique of acetyl normal propyl alcohol |
| CN110052049A (en) * | 2019-05-24 | 2019-07-26 | 山东一诺生物质材料有限公司 | The device and method of 2- methylfuran continuously hydrogen adding production acetyl normal propyl alcohol |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110862310A (en) | 2020-03-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110862310B (en) | Synthesis method of cyclopropyl methyl ketone | |
| CN109232537B (en) | Preparation method of Vonoprazan | |
| CN108558679B (en) | Synthetic method of Parylene A precursor | |
| CN102020543B (en) | Method for producing 9-fluorenone | |
| CN112979498A (en) | Preparation method of 3-fluoro-4-trifluoromethyl benzonitrile | |
| CN108530301B (en) | Synthetic method of 2,4, 6-trifluorobenzylamine | |
| CN108752217B (en) | Synthesis method of dolutegravir key intermediate 2, 4-difluorobenzylamine | |
| CN115504870B (en) | Preparation method and application of 4-methoxy-2-naphthol | |
| CN110818591A (en) | Preparation method of methyl 3,4,5, 6-tetrachloro-2-cyanobenzoate | |
| CN112552184A (en) | Synthetic method of cyclopropyl-containing chiral amine hydrochloride | |
| CN114702402B (en) | Synthetic method of fluoro-phenyl amino acid hydrochloride | |
| CN117550981B (en) | Preparation method of 2-amino-5-fluoro acetophenone | |
| CN111170932A (en) | Preparation method of 2-aminomethyl-5-trifluoromethyl pyridine salt | |
| AU750745B2 (en) | A method of producing aminocyanoacetamide | |
| CN109053462A (en) | A kind of preparation method of para-fluoroaniline | |
| CN113480415B (en) | Process for synthesizing glyoxal by hydroformylation of acrolein | |
| CN114426516B (en) | Preparation method of 2-amino-3-bromopyridine | |
| CN107445850B (en) | Preparation method of 12-aminododecanoic acid | |
| CN109384641B (en) | Synthesis method of 1, 2-vicinal diol compound | |
| CN110437113B (en) | Synthesis method of 4-benzenesulfonylbenzoic acid | |
| CN115636740A (en) | Synthesis process of cyclopropyl formaldehyde | |
| CN117623901A (en) | Preparation method of p-phenylbutoxy benzoic acid | |
| CN115521238A (en) | Preparation method of N-methyl-2- (2-chloroethyl) pyrrolidine | |
| CN117247347A (en) | Preparation method of N-Boc-4-aminopiperidine | |
| CN116947610A (en) | New synthetic route for cyclobutanone |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |