CN1733726A

CN1733726A - N-methylphthalimide preparation process

Info

Publication number: CN1733726A
Application number: CN 200410053743
Authority: CN
Inventors: 瞿渊义
Original assignee: Individual
Current assignee: Individual
Priority date: 2004-08-13
Filing date: 2004-08-13
Publication date: 2006-02-15
Anticipated expiration: 2024-08-13
Also published as: CN1285577C

Abstract

The invention relates to a process for preparing N-methyl-o-phthalimide, which comprises, using benzoic anhydride as raw material, purging methylamine gas for reaction at the presence of inert gas without solvent, dripping water-soluble solvent after the reaction finishes, depositing N-methyl-o-phthalimide crystal, drying and filtering to obtain the end product.

Description

The preparation technology of N-methyl phthalimide

One, technical field

The present invention relates to N-methyl phthalimide preparation method.

Two, background technology:

N-methyl phthalimide English name N-Methyl-o-phthalimide; be called for short NMP, NMP is a kind of important chemical material, because that it contains H on (N-methyl) is very active and contain the aromatic hydrocarbons structure; can be used as synthetic drugs, the intermediate of dye well sterilant.In recent years, NMP is applied to synthetic chemistry luminescence immunoassay reagent, and the potential application prospect will be arranged, and therefore, the Study of synthesis method of this compound seems and becomes more and more important.

Synthetic about NMP, the domestic and foreign literature report, synthetic method mainly contains A, B and big class.Category-A is to make sylvite with phthalic imidine at dehydrated alcohol and potassium hydroxide reaction, and sylvite and methyl-sulfate carry out the alkylated reaction preparation in acetone or acetonitrile solvent.

(1), reaction formula is as follows:

(2), its preparation process is: with the raw material phthalic imidine, potassium hydroxide, dehydrated alcohol adds in the reactor, cooling in stirring reaction 2-3 hour refluxes, put into the suction filtration bucket, take out and contain water-ethanol, take out repeatedly with acetone then and wash the intact raw material of unreacted, imines sylvite joins in the methylation reaction still, add solvent acetone and the methyl-sulfate methylation reaction that refluxes again, fractionate out the intact methyl-sulfate of acetone and unreacted then, the crystallizer tank crystallization is put in cooling, crystal dries through whizzer, uses the small amount of acetone rinsing, the thick NMP that obtains will be in acetone solvent recrystallization.

This NMP synthesis technique long flow path, the solvent recuperation workload is big, and the methyl-sulfate raw material is a severe toxicity, the operational facilities sealing, product purity is low, and recovery rate is low.

Category-B is to use phthalic anhydride under toluene solvant, adds 40% aqueous methylamine solution reaction backflow band water,

(1) reaction formula is as follows:

(2), its preparation process is: raw material phthalic anhydride, 40% aqueous methylamine solution, toluene solvant are added in the reactor, carry out the reaction of refluxing toluene band water, toluene is removed in fractionation again when being with moisture to heat up in a steamer to terminal repeatedly, put into crystallizer tank and separate out crystal, crystal is drained solvent and is removed toluene with the acetone rinsing, and crystal is put into the recrystallization still and carried out recrystallization with acetone then.

This NMP synthesis technique has side reaction, generates byproduct, phthalic acid, and N-methyl o-benzoyl amine formic acid is through the progressively ring-closure reaction of band water, long reaction time.Toluene is poisonous raw material, operation, and machine maintenance, environmental pollution is big.And the difficult cleaning of toluene in the xln, wastewater treatment is arranged, so product purity is not high, recovery rate 85%.

Three, summary of the invention

The purpose of this invention is to provide a kind of preparation technology of new N-methyl phthalimide, the technical issues that need to address are: simplify preparation technology's flow process, improve speed of response, improve recovery rate and product purity, eliminate environmental pollution.Technical scheme of the present invention is: with phthalic anhydride is raw material, under the solvent-free condition that rare gas element arranged, feeds the methylamine gas reaction, and reaction is added dropwise to water-soluble solvent after finishing, and separates out N-methyl phthalimide crystal, dries to filter to get product.

(1), reaction formula is:

(2), in the reaction: the proportioning of phthalic anhydride, methylamine is: 99% phthalic anhydride: 99.9% methylamine=1: 1.05-1: 1.3, water-soluble solvent can be a kind of in water, methyl alcohol, ethanol, propyl alcohol, acetone, methyl ethyl ketone, dioxane, the dimethyl formamide, rare gas element can be nitrogen, helium etc., and the NMP product in water-soluble solvent solubleness is: 3%-50%.

(3), concrete preparation method is: drop into phthalic anhydride in reaction vessel, controlled temperature stirs and feeds methylamine gas at 130 degree-300 degree under protection of inert gas; reaction 1-4 hour joins reaction mixture in the water-soluble solvent, separates out white crystal; filter the dry finished product that gets.

The invention has the beneficial effects as follows: the present invention adopts the direct one-step synthesis of aliphatic amide, and having got rid of with hypertoxic methyl-sulfate is the synthesis technique of raw material, has reduced production cost, shortened preparation technology's flow process, improved environmental quality, waste water obtains good treatment, has improved product purity.The positive effect of implementing after this technology is that starting material react completely, and speed of response is fast, no side reaction and non-environmental-pollution, NMP purity is up to 99.5%, and recovery rate is up to 96%, productive labor rate height, cost is low, and reaction system of the present invention and the contrast of old technology technology are as follows:

Reaction system of the present invention and old technology technology contrast table

Method	The reaction system raw material	Solvent		Operational condition			Solvent washing	Recovery rate %	Product purity %
		Solvent		Operational condition						Charging capacity	Loss %	Flow process	Time h	Environment
		A class technology	Imines ethanol potassium hydroxide acetone methyl-sulfate	Many	70	Long				Charging capacity	Loss %	Flow process	Time h	Environment	6	Harmful	The flush away methyl-sulfate	77	92
B class technology	Phthalic anhydride toluene acetone aqueous methylamine solution	A class technology	Imines ethanol potassium hydroxide acetone methyl-sulfate	Many	70	Long	Greatly	50	In	8	Poisonous	Flush away toluene	85	96	6	Harmful	The flush away methyl-sulfate	77	92
B class technology		Technology of the present invention	Phthalic anhydride methylamine gas water-soluble solvent rare gas element	Little	16	Short	Greatly	50	In	8	Poisonous	Flush away toluene	85	96	4	Do not have	Do not wash	95	99.5

Four, embodiment

Embodiment 1: drop into 200 gram phthalic anhydrides in 250ml four-hole glass reaction bottle; under the helium protection, heat 140 ± 10 ℃; feed methylamine gas 46 grams; reacted 4 hours, and be added dropwise to while hot in the container of 500 gram dioxane solvents and separate out crystal, filter; dry; obtain white crystal 206.7 grams, productive rate reaches 95%, and purity reaches 99.4%.

Embodiment 2: drop into 400 gram phthalic anhydrides and heat under nitrogen protection in 500ml four-hole glass reaction bottle; 180 ± 10 ℃; stir and feed 90 gram methylamine gas reactions 2.5 hours; be added dropwise to while hot in the container of 900 gram dimethylformamide dimethyl amide solvents and separate out white crystal; filter, drying obtains white crystal 413 grams; productive rate reaches 95%, and purity reaches 99.6%.

Embodiment 3: drop into 800 gram phthalic anhydrides and heat under nitrogen protection in 1000ml four-hole glass reaction bottle; 220 ± 10 ℃; stir and feed 180 gram methylamine gas reactions 2 hours; be added dropwise to while hot 1800 the gram alcohol solvents container in separate out white crystal; filter; drying obtains white crystal 844 grams, and productive rate reaches 97%, and purity reaches 99.7%.

Embodiment 4: drop into 200 gram phthalic anhydrides in 250ml four-hole glass reaction bottle; under nitrogen protection, heat 260 ± 10 ℃; feed methylamine gas 51 grams; reacted 1.5 hours, and be added dropwise to while hot in the container of 500 gram propyl alcohol solvents and separate out crystal, filter; dry; obtain white crystal 205 grams, productive rate reaches 94.8%, and purity reaches 99.5%.

Embodiment 5: drop into 400 gram phthalic anhydride heating under the helium protection in 1000ml four-hole glass reaction bottle; 290 ± 10 ℃; stir and feed 92 gram methylamine gas reactions 1 hour; be added dropwise to while hot in the container of 950 gram methyl ethyl ketone solvents and separate out white crystal; filter; drying obtains white crystal 411 grams, and productive rate reaches 95%, and purity reaches 99.4%.

The present invention combines the product physicochemical characteristic, and the fine solvent that filters out can dissolve 50% material, has only 3% 18 ℃ of solubleness, makes the reactive crystallization yield on average reach 96%, has improved the usefulness of producing.Press Q/IAPK1-2004 through Shanghai City quality of chemical products supervision inspection center fine chemistry industry station and detect, the result is as follows:

Index name	Technical requirements	The actual measurement quality
Index name	Technical requirements	The actual measurement quality	Outward appearance	The white uniform powder	The white uniform powder
Fusing point ℃	132.5-134.5	134.2	Outward appearance	The white uniform powder	The white uniform powder
Fusing point ℃	132.5-134.5	134.2	Content % 〉=	99	99.7
N-R base phthalic imidine %≤	0.3	0.3	Content % 〉=	99	99.7
N-R base phthalic imidine %≤	0.3	0.3	Ash %≤	0.3	0.1

Claims

1, the preparation technology of N-methyl phthalimide is characterized in that: with phthalic anhydride is raw material, under the solvent-free condition that rare gas element arranged, the reaction of feeding methylamine gas, reaction is added dropwise to water-soluble solvent after finishing, and separates out N-methyl phthalimide crystal, dries to filter to get product.

2, the preparation technology of N-methyl phthalimide according to claim 1 is characterized in that: the proportioning of phthalic anhydride, methylamine is: 99% phthalic anhydride: 99.9% methylamine=1: 1.05-1: 1.3.

3, the preparation technology of N-methyl phthalimide according to claim 1 is characterized in that: water-soluble solvent can be a kind of in water, methyl alcohol, ethanol, propyl alcohol, acetone, methyl ethyl ketone, dioxane, the dimethyl formamide.

4, the preparation technology of N-methyl phthalimide according to claim 1 is characterized in that: phthalic anhydride and methylamine temperature of reaction are controlled at 130 degree-300 degree, and the reaction times is 1-4 hour.