CN101591263B - Method for preparing N-ethyl-2-isopropyl-5-methycyclohexane - Google Patents
Method for preparing N-ethyl-2-isopropyl-5-methycyclohexane Download PDFInfo
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- CN101591263B CN101591263B CN200910144058A CN200910144058A CN101591263B CN 101591263 B CN101591263 B CN 101591263B CN 200910144058 A CN200910144058 A CN 200910144058A CN 200910144058 A CN200910144058 A CN 200910144058A CN 101591263 B CN101591263 B CN 101591263B
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Abstract
The invention discloses a method for preparing N-ethyl-2-isopropyl-5-methycyclohexane, and belongs to the technical field of amide preparation. The method comprises the following steps: using mint alkyl chloride as a raw material and ethyl bromide as an initiator to firstly prepare chlorinated mint alkyl magnesium; then using trichloromethyl carbonate to prepare mint acyl chloride; and finally obtaining the N-ethyl-2-isopropyl-5-methycyclohexane through the aminolysis reaction of the mint acyl chloride and mono ethyl amine. The method has the advantages of simplicity, simple and convenient operation, mild reaction condition and low production cost; the yield of a product can reach about 80 percent; and the purity of the product reaches more than 99.2 percent. The product prepared by the method has intense cooling flavor effect and long taste retention time, and can be widely applied in the industries of food, medicine, cosmetics, tobacco, and the like.
Description
Technical field
The invention belongs to the acid amides preparing technical field, the preparation method of particularly a kind of N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide.
Technical background
Research shows: it is strong that amide of mint has cool flavor effect, and cooling effect is lasting, is not with bitterness; The skin temperature-sensitive with, stingless excitation, the sensation of no calcination; The flavouring effect is obvious, with advantages such as any cool taste substance can both be used well, can be used for industries such as food, medicine, daily use chemicals, tobacco; But because it costs an arm and a leg, limited its use range, therefore amide of mint is carried out study on the synthesis has important economy, social value.
A kind of method of existing preparation N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide is from the peppermint alkyl chloride, makes product through steps such as grignard reaction, acidifying, chloride, amidations." efficient freshener---the preparation method of amidation Natural menthol " patent like publication number CN1613845; Disclose from Therapeutic Mineral Ice, through prepared amidation Natural menthols such as chloro, grignard reaction, acidifying, chloride, amidation, recrystallizations; The weak point of this method is that reaction conditions is strict in the acidification step, and yield is lower.Another kind method is earlier the peppermint alkyl chloride to be converted into prussiate, and reaction obtains product through Ritter then.Like " coolant agent N-ethyl-L-menthyl methane amide is synthetic " literary composition of fine chemistry industry in November, 2008 o. 11th, introduced Therapeutic Mineral Ice process chloro, cyanic acidization, reaction obtains product through Ritter then; The weak point of this method is in the cyanic acid process, and it is extremely low that menthyl chlorine generates peppermint cyanogen reaction yield as midbody and sodium cyanide reaction, and sodium cyanide is highly toxic substance, increased the difficulty of production operation.
Summary of the invention
The objective of the invention is deficiency, provide a kind of yield and purity higher to existing acid amides preparation method, and the preparation method of the N-that synthetic route is simple, reaction conditions is gentle, production cost is low ethyl-2-sec.-propyl-5-methylcyclohexane methane amide.
Technical scheme of the present invention is: the preparation method of a kind of N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide is characterized in that its method steps:
(1) preparation of chlorination peppermint alkyl magnesium
According to the peppermint alkyl chloride: the mol ratio of magnesium 1: 1～4, the peppermint alkyl chloride is put in the THF of its 1～5 times of mole number, make peppermint alkyl chloride mixed solution; According to magnesium: the mol ratio of THF 1: 1～5, magnesium and THF are put in the container successively, press magnesium again: monobromethane 10～100: 1 mol ratio drops into monobromethane; Under agitation condition, drip above-mentioned peppermint alkyl chloride mixed solution, after dropwising, through insulation reaction, be cooled to room temperature, chlorination peppermint alkyl magnesium;
(2) preparation of peppermint acyl chlorides
In being provided with the container of device for absorbing tail gas, drop into above-mentioned chlorination peppermint alkyl magnesium, under nitrogen protection; According to chlorination peppermint alkyl magnesium: the mol ratio of trichloromethyl carbonate 1: 1～4 under the agitation condition, adds trichloromethyl carbonate; After heating up, reacting, room temperature condensation, crystallization go out excessive solid phosgene; Filter, get the peppermint acyl chlorides;
(3) preparation of N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide
According to the peppermint acyl chlorides: the mol ratio of sodium hydroxide 1: 2～6, the preparation massfraction is 5～20% sodium hydroxide solution, sodium hydroxide solution is joined in the container, by the peppermint acyl chlorides: the mol ratio of monoethylamine 1: 2～8; Under agitation condition, add monoethylamine, insulation drips above-mentioned peppermint acyl chlorides; Control reaction temperature dropwises, after continuing to react, and static layering; Separatory collection organic phase, the organic phase washing is reclaimed THF to neutral, gets N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide bullion; Behind this bullion recrystallization, filter, get N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide.
Its technique effect is: the present invention is a raw material with the peppermint alkyl chloride, and THF is made solvent, and monobromethane is made initiator, makes chlorination peppermint alkyl magnesium earlier; Utilize solid phosgene and chlorination peppermint alkyl reactive magnesium to prepare the peppermint acyl chlorides again; Make N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide product through peppermint acyl chlorides and monoethylamine generation aminolysis reaction at last, its product yield can reach about 80.6%, and purity is up to more than 99.2%.Compared with prior art, omitted acidification step, made that operation is more simple, reaction conditions is gentle, and production cost reduces, and environmental pollution reduces.
Embodiment
Below in conjunction with embodiment, further specify the present invention.
Embodiment 1.
(1) preparation of chlorination peppermint alkyl magnesium
According to the peppermint alkyl chloride: 1: 2 mol ratio of magnesium, the peppermint alkyl chloride is put in the THF of its 3 times of mole numbers, make peppermint alkyl chloride mixed solution; According to magnesium: THF 1: 2 mol ratio, magnesium and THF are put in the dry there-necked flask that tap funnel, TM and reflux condensing tube are housed successively, press magnesium again: 15: 1 mol ratio of monobromethane drops into monobromethane; Under agitation condition, the above-mentioned peppermint alkyl chloride mixed solution of speed dropping with 5mL/min after dropwising, at 80 ℃ of following insulation reaction 2h, is cooled to room temperature, gets chlorination peppermint alkyl magnesium.
(2) preparation of peppermint acyl chlorides
In being provided with the flask of device for absorbing tail gas, drop into above-mentioned chlorination peppermint alkyl magnesium, under nitrogen protection, according to chlorination peppermint alkyl magnesium: 1: 2 mol ratio of trichloromethyl carbonate (popular name solid phosgene); Under the agitation condition, add trichloromethyl carbonate, be warming up to 70 ℃, reaction 2h; Room temperature condensation, crystallization go out excessive solid phosgene, filter; Reclaim filter residue, collect filtrating, get the peppermint acyl chlorides.
(3) preparation of N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide
According to the peppermint acyl chlorides: 1: 3 mol ratio of sodium hydroxide, the preparation massfraction is 7% sodium hydroxide solution, sodium hydroxide solution is joined in the there-necked flask that TM, tap funnel and device for absorbing tail gas are housed, by the peppermint acyl chlorides: 1: 3 mol ratio of monoethylamine; Under agitation condition, add monoethylamine, keep the interior liquid temperature of flask at 15 ℃, the speed with 5mL/min drips above-mentioned peppermint acyl chlorides again; Control reaction temperature dropwises at 5 ℃, continues reaction 0.6h, static layering; Separatory is collected organic phase, and the organic phase washing is reclaimed THF to neutral; N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide bullion, with this bullion recrystallization 2 times, filter; Abandon filtrating, collect filter residue, get white crystal, scentless N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide.Its yield is 79.1%, and purity is 99.2%.
Embodiment 2.
According to the peppermint alkyl chloride: 1: 1 mol ratio of magnesium, the peppermint alkyl chloride is put in the THF of its 1 times of mole number, make peppermint alkyl chloride mixed solution; According to magnesium: THF 1: 1 mol ratio, magnesium and THF are put in the flask successively, press magnesium again: 10: 1 mol ratio of monobromethane drops into monobromethane; Under agitation condition, the above-mentioned peppermint alkyl chloride mixed solution of speed dropping with 4mL/min after dropwising, at 50 ℃ of following insulation reaction 1h, is cooled to room temperature, gets chlorination peppermint alkyl magnesium.
In being provided with the flask of device for absorbing tail gas, drop into above-mentioned chlorination peppermint alkyl magnesium, under nitrogen protection, according to chlorination peppermint alkyl magnesium: 1: 1 mol ratio of trichloromethyl carbonate; Under the agitation condition, add trichloromethyl carbonate, be warming up to 60 ℃, reaction 1h; Room temperature condensation, crystallization go out excessive solid phosgene, filter; Reclaim filter residue, collect filtrating, get the peppermint acyl chlorides.
According to the peppermint acyl chlorides: 1: 2 mol ratio of sodium hydroxide, the preparation massfraction is 5% sodium hydroxide solution, sodium hydroxide solution is added in the flask, by the peppermint acyl chlorides: 1: 2 mol ratio of monoethylamine; Under agitation condition, add monoethylamine, keep the interior liquid temperature of flask at 0 ℃, the speed with 4mL/min drips above-mentioned peppermint acyl chlorides again; Control reaction temperature dropwises at-10 ℃, continues reaction 0.5h, static layering; Separatory is collected organic phase, and the organic phase washing is reclaimed THF to neutral; N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide bullion, with this bullion recrystallization 1 time, filter; Abandon filtrating, collect filter residue, get white crystal, scentless N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide.Its yield is 78.8%, and purity is 99.6%.
Embodiment 3.
According to the peppermint alkyl chloride: 1: 4 mol ratio of magnesium, the peppermint alkyl chloride is put in the THF of its 5 times of mole numbers, make peppermint alkyl chloride mixed solution; According to magnesium: THF 1: 5 mol ratio, magnesium and THF are put in the flask successively, press magnesium again: 100: 1 mol ratio of monobromethane drops into monobromethane; Under agitation condition, the above-mentioned peppermint alkyl chloride mixed solution of speed dropping with 12mL/min after dropwising, at 100 ℃ of following insulation reaction 6h, is cooled to room temperature, gets chlorination peppermint alkyl magnesium.
In being provided with the flask of device for absorbing tail gas, drop into above-mentioned chlorination peppermint alkyl magnesium, under nitrogen protection, according to chlorination peppermint alkyl magnesium: 1: 4 mol ratio of trichloromethyl carbonate; Under the agitation condition, add trichloromethyl carbonate, be warming up to 100 ℃, reaction 10h; Room temperature condensation, crystallization go out excessive solid phosgene, filter; Reclaim filter residue, collect filtrating, get the peppermint acyl chlorides.
According to the peppermint acyl chlorides: 1: 6 mol ratio of sodium hydroxide, the preparation massfraction is 20% sodium hydroxide solution, sodium hydroxide solution is added in the flask, by the peppermint acyl chlorides: 1: 8 mol ratio of monoethylamine; Under agitation condition, add monoethylamine, keep the interior liquid temperature of flask at 20 ℃, the speed with 12mL/min drips above-mentioned peppermint acyl chlorides again; Control reaction temperature dropwises at 15 ℃, continues reaction 3h, static layering; Separatory is collected organic phase, and the organic phase washing is reclaimed THF to neutral; N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide bullion, with this bullion recrystallization 3 times, filter; Abandon filtrating, collect filter residue, get white crystal, scentless N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide.Its yield is 80.6%, and purity is 99.8%.
Claims (1)
1. the preparation method of N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide is characterized in that its method steps:
(1) preparation of chlorination peppermint alkyl magnesium
According to the peppermint alkyl chloride: the mol ratio of magnesium 1: 1～4, the peppermint alkyl chloride is put in the THF of its 1～5 times of mole number, make peppermint alkyl chloride mixed solution; According to magnesium: the mol ratio of THF 1: 1～5, magnesium and THF are put in the container successively, press magnesium again: monobromethane 10～100: 1 mol ratio drops into monobromethane; Under agitation condition, drip above-mentioned peppermint alkyl chloride mixed solution, after dropwising, through insulation reaction, be cooled to room temperature, chlorination peppermint alkyl magnesium;
(2) preparation of peppermint acyl chlorides
In being provided with the container of device for absorbing tail gas, drop into above-mentioned chlorination peppermint alkyl magnesium, under nitrogen protection; According to chlorination peppermint alkyl magnesium: the mol ratio of trichloromethyl carbonate 1: 1～4 under the agitation condition, adds trichloromethyl carbonate; After heating up, reacting, room temperature condensation, crystallization go out excessive solid phosgene; Filter, get the peppermint acyl chlorides;
(3) preparation of N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide
According to the peppermint acyl chlorides: the mol ratio of sodium hydroxide 1: 2～6, the preparation massfraction is 5～20% sodium hydroxide solution, sodium hydroxide solution is joined in the container, by the peppermint acyl chlorides: the mol ratio of monoethylamine 1: 2～8; Under agitation condition, add monoethylamine, insulation drips above-mentioned peppermint acyl chlorides; Control reaction temperature dropwises, after continuing to react, and static layering; Separatory collection organic phase, the organic phase washing is reclaimed THF to neutral, gets N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide bullion; Behind this bullion recrystallization, filter, get N-ethyl-2-sec.-propyl-5-methylcyclohexane methane amide.
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| CN200910144058A CN101591263B (en) | 2009-07-07 | 2009-07-07 | Method for preparing N-ethyl-2-isopropyl-5-methycyclohexane |
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Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102964268A (en) * | 2012-10-27 | 2013-03-13 | 安徽丰乐香料有限责任公司 | Synthesis method of menthyl amide cooling agent |
| CN103665038B (en) * | 2013-12-26 | 2015-11-25 | 聊城大学 | A kind of carbon phosphorus chirality dialkyl phosphine oxide and synthetic method thereof |
| CN104496836B (en) * | 2014-11-27 | 2016-06-29 | 安徽丰乐香料有限责任公司 | A kind of industrial method removing N, 2,3-trimethyl-2-butanamide mother liquor impurity |
| CN106946729B (en) * | 2017-03-27 | 2018-10-16 | 万华化学集团股份有限公司 | A kind of preparation method of L- N-Ethyl-p-menthane-3-carboxamide class compound |
| TWI845505B (en) * | 2018-04-11 | 2024-06-21 | 日商三菱瓦斯化學股份有限公司 | Method for producing 1,4-cyclohexanedicarboxylic acid derivative, 1,4-dicyanocyclohexane, and 1,4-bis(aminomethyl)cyclohexane |
| CN109851522B (en) * | 2018-12-10 | 2022-03-11 | 万华化学集团股份有限公司 | Method for preparing N-ethyl-L-menthyl formamide by inversion of N-ethyl-neo-menthyl formamide configuration |
| CN112939801A (en) * | 2021-02-03 | 2021-06-11 | 安徽中草香料股份有限公司 | Process for synthesizing cooling agent |
| CN115160184A (en) * | 2022-08-08 | 2022-10-11 | 安徽丰乐香料有限责任公司 | Preparation method of N-p-phenylacetonitrile menthane alkyl formamide |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4350832A (en) * | 1981-04-27 | 1982-09-21 | Philip Morris, Incorporated | Synthesis of N-t-butyl-p-menthane-3-carboxamide |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4350832A (en) * | 1981-04-27 | 1982-09-21 | Philip Morris, Incorporated | Synthesis of N-t-butyl-p-menthane-3-carboxamide |
Non-Patent Citations (2)
| Title |
|---|
| 田红玉等.凉味剂N-乙基-L-薄荷基甲酰胺的合成.《精细化工》.2008,第25卷(第11期),1097-1110下转1113页. * |
| 莫卫民等.固体光气在酰氯制备中的应用.《浙江化工》.2004,第35卷(第3期),14-15. * |
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