CN106397243A - Preparation method of N-methyl-4-hydroxybenzamide - Google Patents
Preparation method of N-methyl-4-hydroxybenzamide Download PDFInfo
- Publication number
- CN106397243A CN106397243A CN201610846004.0A CN201610846004A CN106397243A CN 106397243 A CN106397243 A CN 106397243A CN 201610846004 A CN201610846004 A CN 201610846004A CN 106397243 A CN106397243 A CN 106397243A
- Authority
- CN
- China
- Prior art keywords
- hydroxybenzamide
- methyl
- methylamine
- preparation
- dropping
- 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
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/14—Preparation of carboxylic acid esters from carboxylic acid halides
Abstract
The invention relates to a preparation method of N-methyl-4-hydroxybenzamide, wherein the preparation method comprises the following steps: 1) adding 4-hydroxybenzoyl chloride and triethylamine into a container, heating under stirring to make the system temperature be 20-50 DEG C, then dropping absolute ethyl alcohol with the dropping time of 0.5-1 h, after the dropping is finished, carrying out a heat preservation reaction for 2-5 h at the temperature of 20-50 DEG C, then carrying out suction filtration of the reaction liquid to remove triethylamine hydrochloride, and thus obtaining a filtrate, namely ethyl 4-hydroxybenzoate; and 2) adding ethyl 4-hydroxybenzoate into the container, stirring and heating to 30-60 DEG C, dropping methylamine with the dropping time of 0.5-1 h, after the dropping is finished, carrying out a heat preservation reaction for 3-5 h at the temperature of 30-60 DEG C, cooling to room temperature, precipitating out a large number of solids, and carrying out suction filtration, to obtain a filter cake, namely N-methyl-4-hydroxybenzamide. Compared with the prior art, with adopting of the stepwise reaction, the yield of N-methyl-4-hydroxybenzamide is greatly improved.
Description
[technical field]
The present invention relates to the preparing technical field of amides compound, specifically a kind of N- methyl -4- hydroxy benzenes first
The preparation method of acid amides.
[background technology]
N- methyl -4- hydroxybenzamide is a medicine intermediate, is also a kind of centre of acetamide-group herbicides simultaneously
Body.When synthesizing N- methyl -4- hydroxybenzamide, because commercially available methylamine is mostly the second with the aqueous solution of methylamine and methylamine
Alcoholic solution is sold, so, the reaction yield being in the past similar to is very low, at this moment due to 4- hydroxybenzoyl chloride and first in building-up process
The alcoholic solution reaction of amine is that a competitive reaction, i.e. 4- hydroxybenzoyl chloride and ethanol synthesis generate ester；4- hydroxybenzoyl chloride
React with methylamine and generate acid amides, and the reaction of 4- hydroxybenzoyl chloride and ethanol generates the reaction speed of 4-HBA ethyl ester
It is greater than 4- hydroxybenzoyl chloride and methylamine reaction generates the speed of N- methyl -4- hydroxybenzamide.Therefore, this reaction is first big
Amount generates 4-HBA ethyl ester, and then, 4-HBA ethyl ester and methylamine reaction generate N- methyl -4- (2-hydroxybenzoyl)
Amine, adds that the boiling point of methylamine is relatively low, and in whole course of reaction, substantial amounts of methylamine escapes reaction system, so, with the second of methylamine
Alcoholic solution directly carries out acylation reaction, and the yield of N- methyl -4- hydroxybenzamide is extremely low.
[content of the invention]
Present invention aim to solving above-mentioned deficiency and providing a kind of preparation of N- methyl -4- hydroxybenzamide
Method, changes 4- hydroxybenzoyl chloride and directly reacts with the ethanol solution of methylamine, but adopt stepwise reaction, make N- methyl-
The yield of 4- hydroxybenzamide increases substantially.
Design a kind of preparation method of the N- methyl -4- hydroxybenzamide of structure formula (I) for achieving the above object, including
Following steps：
1) 4- hydroxybenzoyl chloride, triethylamine are added in a reservoir, the lower heating of stirring makes system temperature drip when 20-50 DEG C
Plus absolute ethyl alcohol, time for adding is 0.5-1h, after completion of dropwise addition, in 20-50 DEG C of insulation reaction 2-5h, then by reactant liquor suction filtration
Remove triethylamine hydrochloride, filtrate is 4-HBA ethyl ester；
2) add 4-HBA ethyl ester in a reservoir, be heated with stirring to 30-60 DEG C of dropping methylamine, time for adding is
0.5-1h, after completion of dropwise addition, after 30-60 DEG C of insulation reaction 3-5h, is cooled to room temperature, has a large amount of solids to separate out, obtains through suction filtration
To filter cake be N- methyl -4- hydroxybenzamide.
Further, step 2) in, filtrate that suction filtration is obtained pour into 10-20 times with the pure water of its volume in, treat solid
Fully separate out, the filter cake that suction filtration obtains is N- methyl -4- hydroxybenzamide, merge above-mentioned two parts filter cake N- methyl -4- hydroxyl
Yl-benzamide, is dried 5-8 hour with 50-70 DEG C.
Preferably, step 1) in, described 4- hydroxybenzoyl chloride, triethylamine, the molar ratio of material of ethanol are 4- hydroxyl
Chlorobenzoyl chloride：Triethylamine：Ethanol=1:1:1-1.2.
Preferably, step 2) in, described methylamine is the ethanol solution of 30% methylamine.
Preferably, step 2) in, described 4-HBA ethyl ester, the molar ratio of material of methylamine are 4-HBA
Ethyl ester：Methylamine=1:1-1.2.
Preferably, described container is the four-hole boiling flask with agitator, thermometer, condenser pipe and dropping funel.
The present invention compared with the existing technology, changes direct and methylamine the ethanol solution of 4- hydroxybenzoyl chloride and reacts, and
It is to adopt stepwise reaction, first make 4- hydroxybenzoyl chloride and absolute ethyl alcohol reaction generate 4-HBA ethyl ester, then, by first
The ethanol solution of amine drops in the 4-HBA ethyl ester of uniform temperature, so easily makes 4-HBA ethyl ester
React with the methylamine in methylethylolamine solution and generate N- methyl -4- hydroxybenzamide, substantially increase N- methyl -4- hydroxyl
The yield of yl-benzamide.
[specific embodiment]
The invention provides a kind of preparation method of the N- methyl -4- hydroxybenzamide of structure formula (I), walk including following
Suddenly：
1) 4- hydroxybenzoyl chloride, triethylamine are added in a reservoir, the lower heating of stirring makes system temperature drip when 20-50 DEG C
Plus absolute ethyl alcohol, time for adding is 0.5-1h, in 20-50 DEG C of insulation reaction 2-5h after completion of dropwise addition, then by reactant liquor suction filtration
Remove triethylamine hydrochloride, filtrate is 4-HBA ethyl ester.
2) add 4-HBA ethyl ester in a reservoir, be heated with stirring to 30-60 DEG C of dropping methylamine, time for adding is
0.5-1h, after completion of dropwise addition, after 30-60 DEG C of insulation reaction 3-5h, is cooled to room temperature, has a large amount of solids to separate out, obtains through suction filtration
To filter cake be N- methyl -4- hydroxybenzamide；Filtrate pour into 10-20 times with the pure water of its volume in, treat that solid is fully analysed
Go out, the filter cake that suction filtration obtains is N- methyl -4- hydroxybenzamide, merge above-mentioned two parts filter cake N- methyl -4- hydroxy benzenes first
Acid amides, then, is dried 5-8 hour with 50-70 DEG C.
Wherein, step 1) in, molar ratio of material 4- hydroxybenzoyl chloride：Triethylamine：Ethanol=1:1-1.2:1-1.2；Step
In rapid 2), molar ratio of material 4-HBA ethyl ester：Methylamine=1:1-1.2, methylamine used is that the ethanol of 30% methylamine is molten
Liquid；Step 1) and step 2) in, container can be selected for the four-hole boiling flask with agitator, thermometer, condenser pipe and dropping funel.
With reference to specific embodiment, the present invention is made further explained below：
Embodiment 1
25g (0.16mol) 4- hydroxybenzoyl chloride is added with agitator, thermometer, condenser pipe and dropping funel
In 250mL four-hole boiling flask, add 16g triethylamine, be heated to 40 DEG C.Drip 8.0g absolute ethyl alcohol under agitation, then, in 40 DEG C
Insulation reaction 4h.After reaction terminates, reactant liquor suction filtration is removed triethylamine hydrochloride, filtrate is 4-HBA ethyl ester, warp
Weigh as 25g.
25g (0.15mol) 4-HBA ethyl ester is added with the leakage of agitator, thermometer, condenser pipe and dropping liquid
In the 250mL four-hole boiling flask of bucket, it is heated to 50 DEG C, then, the ethanol solution of dropping 15.5g methylamine, in this thermotonus 4h, cold
But, suction filtration, washing and drying obtain 18.8gN- methyl -4- hydroxybenzamide.Total recovery is more than 85%, fusing point：115.8～116
℃.IR(KBr),v/cm-1：3218.9cm-1(H-O), 3187.5cm-1(N-H), 1674.2 (C=O), 1240.3cm-1(C-O)；1HNMR：10.3 (s, 1H ,-OH), 7.8 (2H ,-C6H4-), 6.85 (2H ,-C6H4-), 4.25 (d, 3H ,-CH3), 1.3 (s, 1H ,-
NH-).
Embodiment 2
25g (0.16mol) 4- hydroxybenzoyl chloride is added with agitator, thermometer, condenser pipe and dropping funel
In 250mL four-hole boiling flask, add 16g triethylamine, be heated to 20 DEG C.Drip 8.0g absolute ethyl alcohol under agitation, then, in 20 DEG C
Insulation reaction 4h.After reaction terminates, reactant liquor suction filtration is removed triethylamine hydrochloride, filtrate is 4-HBA ethyl ester, warp
Weigh as 16g.
16g (0.1mol) 4-HBA ethyl ester is added with agitator, thermometer, condenser pipe and dropping funel
250mL four-hole boiling flask in, be heated to 30 DEG C, then, the ethanol solution of dropping 10.5g methylamine, in this thermotonus 4h, cold
But, suction filtration, washing and drying obtain 9.6gN- methyl -4- hydroxybenzamide.Total recovery is about 43.8%.
Embodiment 3
25g (0.16mol) 4- hydroxybenzoyl chloride is added with agitator, thermometer, condenser pipe and dropping funel
In 250mL four-hole boiling flask, add 16g triethylamine, be heated to 30 DEG C.Drip 8.0g absolute ethyl alcohol under agitation, then, in 30 DEG C
Insulation reaction 4h.After reaction terminates, reactant liquor suction filtration is removed triethylamine hydrochloride, filtrate is 4-HBA ethyl ester, warp
Weigh as 18.5g.
18.5g (0.11mol) 4-HBA ethyl ester is added with agitator, thermometer, condenser pipe and dropping liquid
In the 250mL four-hole boiling flask of funnel, it is heated to 45 DEG C, then, the ethanol solution of dropping 11.5g methylamine, in this thermotonus 4h,
Cooling, suction filtration, washing and drying obtain 12.5gN- methyl -4- hydroxybenzamide.Total recovery is more than 57%.
Embodiment 4
25g (0.16mol) 4- hydroxybenzoyl chloride is added with agitator, thermometer, condenser pipe and dropping funel
In 250mL four-hole boiling flask, add 16g triethylamine, be heated to 40 DEG C.Drip 8.0g absolute ethyl alcohol under agitation, then, in 40 DEG C
Insulation reaction 4h.After reaction terminates, reactant liquor suction filtration is removed triethylamine hydrochloride, filtrate is 4-HBA ethyl ester, warp
Weigh as 25g.
25g (0.15mol) 4-HBA ethyl ester is added with the leakage of agitator, thermometer, condenser pipe and dropping liquid
In the 250mL four-hole boiling flask of bucket, it is heated to 60 DEG C, then, the ethanol solution of dropping 15.5g methylamine, in this thermotonus 4h, cold
But, suction filtration, washing and drying obtain 17.5gN- methyl -4- hydroxybenzamide, and total recovery is more than 70.8%.
Embodiment 5
25g (0.16mol) 4- hydroxybenzoyl chloride is added with agitator, thermometer, condenser pipe and dropping funel
In 250mL four-hole boiling flask, add 16g triethylamine, be heated to 20 DEG C.Drip 8.0g absolute ethyl alcohol under agitation, then, in 20 DEG C
Insulation reaction 4h.After reaction terminates, reactant liquor suction filtration is removed triethylamine hydrochloride, filtrate is 4-HBA ethyl ester, warp
Weigh as 16g.
16g (0.1mol) 4-HBA ethyl ester is added with agitator, thermometer, condenser pipe and dropping funel
250mL four-hole boiling flask in, be heated to 30 DEG C, then, the ethanol solution of dropping 10.5g methylamine, in this thermotonus 4h, cold
But, suction filtration, washing and drying obtain 9.6gN- methyl -4- hydroxybenzamide.Again by filtrate pour into 10-20 times pure with its volume
In water, treat that solid fully separates out, the filter cake that suction filtration obtains is N- methyl -4- hydroxybenzamide, merge above-mentioned two parts filter cake
N- methyl -4- hydroxybenzamide, then, is dried 5-8 hour with 50-70 DEG C.Total recovery is much larger than 43.8%.
Embodiment 6
25g (0.16mol) 4- hydroxybenzoyl chloride is added with agitator, thermometer, condenser pipe and dropping funel
In 250mL four-hole boiling flask, add 16g triethylamine, be heated to 50 DEG C.Drip 8.0g absolute ethyl alcohol under agitation, time for adding is
0.5-1h, after completion of dropwise addition, in 50 DEG C of insulation reaction 5h.After reaction terminates, reactant liquor suction filtration is removed triethylamine hydrochloride, filter
Liquid is 4-HBA ethyl ester.
Gained 4-HBA ethyl ester is added the 250mL with agitator, thermometer, condenser pipe and dropping funel
In four-hole boiling flask, it is heated to 50 DEG C, then, the ethanol solution of dropping 15.5g methylamine, time for adding is 0.5-1h, completion of dropwise addition
Afterwards, in this thermotonus 5h, cooling, suction filtration, washing and drying obtain N- methyl -4- hydroxybenzamide.Total recovery is more than to be implemented
The total recovery of example 1.
Comparative example
25g (0.16mol) 4- hydroxybenzoyl chloride is added with agitator, thermometer, condenser pipe and dropping funel
In 250mL four-hole boiling flask, add 16g triethylamine, be heated to 40 DEG C, the ethanol solution of dropping 17g methylamine, in this thermotonus
4h, cooling, suction filtration, washing and drying obtain 5.5gN- methyl -4- hydroxybenzamide, and yield is about 25%.
The present invention is not limited by above-mentioned embodiment, other any Spirit Essences without departing from the present invention and principle
Lower made change, modification, replacement, combination, simplification, all should be equivalent substitute mode, are included in the protection model of the present invention
Within enclosing.
Claims (6)
1. a kind of preparation method of N- methyl -4- hydroxybenzamide is it is characterised in that comprise the following steps：
1) 4- hydroxybenzoyl chloride, triethylamine are added in a reservoir, the lower heating of stirring makes system temperature drip when 20-50 DEG C no
Water-ethanol, time for adding is 0.5-1h, after completion of dropwise addition, in 20-50 DEG C of insulation reaction 2-5h, then removes reactant liquor suction filtration
Triethylamine hydrochloride, filtrate is 4-HBA ethyl ester；
2) add 4-HBA ethyl ester in a reservoir, be heated with stirring to 30-60 DEG C of dropping methylamine, time for adding is 0.5-
1h, after completion of dropwise addition, after 30-60 DEG C of insulation reaction 3-5h, is cooled to room temperature, has a large amount of solids to separate out, obtains through suction filtration
Filter cake is N- methyl -4- hydroxybenzamide.
2. N- methyl -4- hydroxybenzamide as claimed in claim 1 preparation method it is characterised in that：Step 2) in, will
The filtrate that suction filtration obtains pour into 10-20 times with the pure water of its volume in, treat that solid fully separates out, the filter cake that suction filtration obtains is N- first
Base -4- hydroxybenzamide, merges above-mentioned two parts filter cake N- methyl -4- hydroxybenzamide, 5-8 is dried with 50-70 DEG C little
When.
3. N- methyl -4- hydroxybenzamide as claimed in claim 1 or 2 preparation method it is characterised in that：
Step 1) in, described 4- hydroxybenzoyl chloride, triethylamine, the molar ratio of material of ethanol are 4- hydroxybenzoyl chloride：Three second
Amine：Ethanol=1:1:1-1.2.
4. N- methyl -4- hydroxybenzamide as claimed in claim 1 or 2 preparation method it is characterised in that：
Step 2) in, described methylamine is the ethanol solution of 30% methylamine.
5. N- methyl -4- hydroxybenzamide as claimed in claim 1 or 2 preparation method it is characterised in that：
Step 2) in, described 4-HBA ethyl ester, the molar ratio of material of methylamine are 4-HBA ethyl ester：Methylamine=1:
1-1.2.
6. N- methyl -4- hydroxybenzamide as claimed in claim 1 or 2 preparation method it is characterised in that：
Described container is the four-hole boiling flask with agitator, thermometer, condenser pipe and dropping funel.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610846004.0A CN106397243A (en) | 2016-09-23 | 2016-09-23 | Preparation method of N-methyl-4-hydroxybenzamide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610846004.0A CN106397243A (en) | 2016-09-23 | 2016-09-23 | Preparation method of N-methyl-4-hydroxybenzamide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106397243A true CN106397243A (en) | 2017-02-15 |
Family
ID=57997887
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610846004.0A Pending CN106397243A (en) | 2016-09-23 | 2016-09-23 | Preparation method of N-methyl-4-hydroxybenzamide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106397243A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108911982A (en) * | 2018-07-19 | 2018-11-30 | 徐州博康信息化学品有限公司 | A kind of environment protection method for the styrene compound that synthesis acyloxy replaces |
-
2016
- 2016-09-23 CN CN201610846004.0A patent/CN106397243A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| FREDERIK E. A. VAN WAES ET AL.: "Efficient and catalyst-free condensation of acid chlorides and alcohols using continuous flow", 《GREEN CHEMISTRY》 * |
| MICHAEL B. SMITH 等编著，李艳梅 译: "《March高等有机化学——反应、机理与结构》", 31 January 2010, 化学工业出版社 * |
| THOMAS HOGBERG ET AL.: "Cyanide as an efficient and mild catalyst in the aminolysis of esters", 《J. ORG. CHEM.》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108911982A (en) * | 2018-07-19 | 2018-11-30 | 徐州博康信息化学品有限公司 | A kind of environment protection method for the styrene compound that synthesis acyloxy replaces |
| CN108911982B (en) * | 2018-07-19 | 2022-08-26 | 徐州博康信息化学品有限公司 | Environment-friendly method for synthesizing acyloxy-substituted styrene compound |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104540821B (en) | The method for preparing some 2 (base of pyridine 3) thiazoles | |
| CN104086379B (en) | The synthetic method of the clean intermediate of Da Gelie | |
| CN106220591B (en) | A kind of preparation method of 3 methyl mercapto gamma lactone | |
| CN103102307A (en) | Method for synthesizing tolfenpyrad | |
| US20100249439A1 (en) | Process for controlled crystal size in 1,2-substituted 3,4-dioxo-1-cyclobutene compounds | |
| CN106946716B (en) | A kind of benzalkonium chloride monomer synthesis technology | |
| CN104817443B (en) | Benzoin dimethyl ether synthesis process | |
| CN102285963B (en) | 3-methoxy pyrazolecarboxamide compound and application thereof | |
| CN106397243A (en) | Preparation method of N-methyl-4-hydroxybenzamide | |
| CN107540648A (en) | A kind of preparation method of Dapagliflozin | |
| CN104402778B (en) | A kind of acrylamide derivative of benzyl sulfonamide substitutions | |
| CN104326992A (en) | Method for synthesizing difluoro methyl triazoline-ketone and sulfentrazone | |
| CN107759528B (en) | Synthesis method of 2-chloro-4, 6-dimethoxypyrimidine | |
| CN106810546A (en) | A kind of umeclidinium compound | |
| CN106916068B (en) | A kind of simple and convenient benzalkonium chloride production method | |
| CN106278914B (en) | A kind of synthesis technique of increase production of amines | |
| CN101391969B (en) | Method for preparing N-methyl-2-(2,4-dichlorophenoxy) acetamide | |
| CN103613615B (en) | A kind of preparation method of PMIDA | |
| CN104557902B (en) | A kind of method for preparing thiabendazole | |
| CN107325063A (en) | A kind of production method of MTI-446 | |
| CN108203392A (en) | A kind of process for cleanly preparing of glycine in coproduction with ammonium chloride | |
| CN107235973A (en) | The preparation method of the adjoining fluorobenzene calcium composition of piperidones chain with pharmaceutical activity | |
| CN106565560A (en) | Synthesis process of mesotrione | |
| CN109134473A (en) | A kind of preparation method of the sweet guanidine of dinitro | |
| CN111875486A (en) | Synthesis method of 2, 6-dimethyl-1-indanone |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170215 |
|
| RJ01 | Rejection of invention patent application after publication |