JPS62178548A - Production of 3-chloro-4-isopropylaniline - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a raw material or intermediate for various agricultural chemicals, in high yield at a low cost with one-step reaction, by using easily available 4-isopropylaniline as a raw material and chlorinating the material in sulfuric acid. CONSTITUTION:4-Isopropylaniline is used as a raw material and chlorinated is sulfuric acid to obtain the objective compound. The chlorination is carried out by directly introducing chlorine gas into reaction liquid. The amount of the chlorine gas introduced into the reaction system is 0.5-15 equivalent, preferably 1.2-5 equivalent based on the raw material. It is effective to introduce the chlorine gas under agitation or in light-shielded state or together with dried air. The yield becomes highest by terminating the chlorination reaction when the residual ratio of the raw material is 3-10% of the whole raw material. The concentration of sulfuric acid is preferably 94-97% and the amount of the acid is preferably 4-7 times equivalent of the raw material.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing 3-chloro-4-isopropylaniline.

3-Chloro-4-isopropylaniline is important as an intermediate for agricultural chemicals, and has been used as a raw material or intermediate for many patented compounds since ancient times.

(JP-A-46-2049, JP-A-46-2050, West German Patent No. 2,249,547, JP-A-52-3
Publication No. 4926, Publication No. 55-157561, Special Publication No. 6
(No. 0-21136) In response to this, the demand has increased in recent years, and its value has been highly evaluated.

The present invention relates to a method for manufacturing 3-chloro-4-isopropylaniline industrially and supplying it at low cost.

[Prior art]

There are very few reports describing the synthesis or production method of 3-chloro-4-isopropylaniline.
In recent years, only West German patents 2,249,547 and 3-
Only a method for obtaining chloro-4-isopropylnitrobenzene by reduction is described.

In this method, it is used as a raw material due to the problem of isomer by-products.

Obtaining 3-chloro-4-isopropylnitrobenzene itself is difficult. Therefore, there are almost no known techniques for producing 3-chloro-4-isopropylaniline either industrially or in the laboratory.

[Problem to be solved by the invention]

An object of the present invention is to provide an industrially simple and economical method for producing 3-chloro-4-isopropylaniline, which is important as a raw material or intermediate for various agricultural chemicals.

[Means and effects for solving the problem] As a result of intensive studies to solve the above problems, the present inventors found that 4-isopropylphenol can be industrially mass-produced by ammonolysis and is easily available. The present invention was completed based on the discovery that the object of the present invention can be achieved by using -isopropylaniline as a raw material and chlorinating it.

That is, the present invention is a method for producing 3-chloro-4-isopropylaniline, which is characterized by chlorinating 4-isopropylaniline in sulfuric acid.

Concentrated sulfuric acid is suitable as the sulfuric acid used in the method of the present invention, and generally has a concentration of 90χ to 100χ, preferably 9
Those with a diameter of 4χ to 97χ are used. The amount of sulfuric acid used varies depending on the reaction temperature, but it is sufficient as long as it is sufficient to dissolve the raw material 4-isopropylaniline.
If the amount is too large, the volumetric efficiency will deteriorate and furthermore, a large amount of base will be required for neutralization after the reaction.
The amount of sulfuric acid used is 1 to 12 times equivalent, more preferably 4 to 7 times equivalent.

In the method of the present invention, it is of course possible to reduce the amount of sulfuric acid used by increasing the reaction temperature, but it is necessary to carry out the reaction at a temperature below which sulfonation does not proceed. Generally, the reaction temperature is -32
The temperature is preferably between 10°C and 100°C, preferably between 0°C and 70°C, and more preferably between 10°C and 50°C.

In the method of the present invention, chlorination is carried out by directly introducing chlorine gas into the reaction solution. In this case, the amount of chlorine gas introduced varies depending on the reaction temperature and reaction time, but is generally 0.5 equivalent to 15 equivalents, preferably 1.1 equivalent to 8 equivalents, and more than 1. Preferably it is 1.2 equivalents to 5 equivalents. Furthermore, by recycling chlorine gas, it is possible to bring the amount of chlorine used closer to the chemical equivalent. Furthermore, it will be more efficient if stirring is performed simultaneously when introducing chlorine gas. Furthermore, more desirable results can be achieved by blocking light or introducing dry air at the same time.

In the method of the present invention, it is possible to continue the chlorination reaction until the raw material 4-isopropylaniline completely disappears, but it is possible to continue the chlorination reaction until the raw material 4-isopropylaniline completely disappears. It is preferable in terms of yield to terminate the chlorination reaction at . The remaining amount of 4-isopropylaniline in the reaction solution was determined by thin layer chromatography (T,
It can be very easily confirmed by analytical means such as L, C), liquid chromatography (L, C), and gas chromatography (GC).

After the reaction is completed, the reaction mixture is preferably diluted with ice water or cold water in an amount of 1 to 10 times the volume of the reaction mixture. At this point, objective 3
- A part of chloro-4-isopropylaniline precipitates as sulfate, and it is possible to recover this, but generally all of the target 3-chloro-4-isopropylaniline is liberated by neutralization. can be done. In this case, as the bases used for neutralization, generally used bases can be used, preferably inorganic bases such as sodium hydroxide, potassium hydroxide, sodium hydrogen carbonate,
Sodium carbonate, potassium carbonate, or their aqueous solutions, or ammonia gas or their aqueous solutions can be used.

The liberated 3-chloro-4-isopropylaniline can be easily purified with non-aqueous solvents such as hexane, benzene, toluene, xylene, petroleum ether, chlorobenzene, ethyl ether, ethyl acetate, chloroform, dichloromethane, carbon tetrachloride, and other organic solvents. Can be extracted. Although 3-chloro-4-isopropylaniline with a purity of 90% or more can be obtained by simply distilling off the extraction solvent from the extract, it is preferable to obtain 3-chloro-4-isopropylaniline with an even higher purity by distilling it. It is possible to obtain isopropylaniline. In this case, the target product can be obtained in a high yield of 80% or more based on the raw material 4-isopropylaniline, although it depends on the distillation method.

〔Example〕

Next, the method of the present invention will be specifically explained with reference to synthesis examples, but the method is not limited thereto.

Synthesis Example 1 In a glass reactor equipped with a dropping funnel, a gas inlet tube and a stirrer, 135 g (1 mol) of 4-isopropylaniline, 96% sulfuric acid and 325 ml of sulfuric acid were added under a dry nitrogen gas atmosphere.
(6 mol) was slowly added dropwise while stirring vigorously. Further, the dropping was performed while cooling at any time so that the temperature did not exceed 50°C. After the dropwise addition was completed, stirring was continued, and when a homogeneous solution was obtained, the reactor was covered with aluminum foil to block light, and chlorine gas was introduced into the reaction solution instead of nitrogen gas. A tube for introducing chlorine gas was used that reached the bottom of the reactor, and vigorous stirring was performed to keep the reaction solution uniform at all times.

Thereafter, the temperature of the reaction solution gradually decreased and became constant at around 25°C to 28°C. After continuing to introduce chlorine gas and stirring for about 5 hours, the reaction solution was poured into ice water, neutralized with sodium hydroxide, and extracted with hexane. The extract was dried over anhydrous sodium sulfate and then concentrated to produce a blackish oil (composition ratio determined by gas chromatography (the same applies hereinafter): 3-chloro-4-isopropylaniline 93.8χ, 4-isopropylaniline 6.2χ, unknown Compound Trace H69
, 6g was obtained. In addition, by distilling this oil under reduced pressure, the first distillation (1) (65"~75℃10.6 og,
! k[l composition: 3-chloro-4-isopropylaniline 45.6χ, 4-isopropylaniline 54.2χ, unknown compound 0.2χ) 5.6g, initial distillation (II) (75
℃～82℃10. flu++ mHg, composition = 3-chloro 4-isopropylaniline 61.4χ, 4-isopropylaniline 38.3χ, unknown compound 0.3χ) 5.1
g, and main distillation (83° to 88°C 10.6 m++w) I
g, composition: 3-chloro-4-isopropylaniline 97
．． Obtained 143.2 g of 8χ, 4-isopropylaniline 2.2χ, unknown compound trace)* NMR/17o:1
．． 1? (6H, d, J'7Hz), 3.28 (IH, m
+), 3.44 (LH,s), 6.39 (LH
, dd, J=8Hz, J=211z), 6.5
4 (IL d.

J-2) 1z), 6.97 (Ill, d, J=8Hz)
, yield of main distillate 84.5χ.

Synthesis Example 2 95χ to 405g (3 mol) of 4-isopropylaniline
813 ml (15 mol) of sulfuric acid was slowly added dropwise while stirring vigorously. Further, the dropwise addition was performed while cooling at any time so that the temperature did not exceed 80'C. After the dropwise addition was completed, stirring was continued, and when the reaction solution became a homogeneous solution, a mixed gas of chlorine j and dry air (chlorine:air 20:1,
volume ratio) was introduced from the bottom of the reactor. Thereafter, the reaction solution gradually decreased and became constant at around 32°C. After continuing to stir and introduce gas for about 12 hours, the reaction solution was poured into ice water, made weakly alkaline with aqueous ammonia, and extracted with ethyl ether. The extract was dried over calcium chloride and concentrated to obtain a dark brown oil. Distill it under reduced pressure 9
By collecting the fraction of 5° to 98°C/1 ma+Hg, 415 g of a colorless and transparent oil was obtained.

NMRδcrc! ::1.1? (6H, d, J-7Hz
), 3.28(1)1. m), 3.44 (IH, s)
, 6.39 (LH, dd, J-8Hz, J-2
Hz), 6.54 (18, d, J-2Hz),
6.97 (LH, d, J=8) 1x), yield 81.6χ
.

(Effects of the Invention) The method for producing 3-chloro-4-isopropylaniline according to the present invention is characterized by chlorinating 4-isopropylaniline, which can be industrially mass-produced, in sulfuric acid. , with high yield and advantages both industrially and in the laboratory.
Moreover, it is possible to economically supply the desired 3-chloro-4-isopropylaniline.

Claims (1)

[Claims] A method for producing 3-chloro-4-isopropylaniline, which comprises chlorinating 4-isopropylaniline in sulfuric acid.