JPS5967232A - Novel method for preparing o-difluorobenzene - Google Patents

Abstract

PURPOSE:To prepare the titled compound useful as a synthetic intermediate for antimicrobial agents in high yield, by adding a small amount of a silicone oil to 2-fluoro-1-benzenediazonium tetrafluoroborate in the thermal decomposition thereof. CONSTITUTION:o-Fluoroaniline is diazotized and then reacted with a fluoronating agent, e.g. borofluoric acid to give 2-fluoro-1-benzenediazonium tetrafluoroborate. A small amount, preferably about 4-5wt% based on the above-mentioned raw material, of a silicone oil is added to the 2-fluoro-1-benzenediazonium tetrafluoroborate and decomposed thermally under heating at 100- 180 deg.C, preferably 130-160 deg.C, for about 1-5hr to afford the aimed o-difluorobenzene. EFFECT:The reaction proceeds very mildly, and a reaction vessel of relatively small volume is enough.

Description

[Detailed description of the invention] The invention relates to a new method for producing O-difluorobenzene.

O-difluorobenzene is a known compound and is useful as a synthetic intermediate for known antibacterial agents (for example, see JP-A-53-141286).

The method for producing O-difluorobenzene is as follows: 2-fluoroaniline obtained by diazotization
- C. Schiemann, who has a known method for thermally decomposing benzenediazonium tetofuroborate
& Pillars, Ber, 52.3Q35(1
929), u and Bergmann, Engel &
5andor.

Z, Physik, Chem,, l0t3.106 (
1930)]. However, this known method has an extremely poor yield, especially in the thermal decomposition process, which yields only 30%
% yield was not listed.

While the inventors were conducting their own research to find an improved method for obtaining this compound in high yield, they unexpectedly discovered that by adding a small amount of silicon to the thermal decomposition of the diazonium salt, It became clear that the target 0-difluorobenzene could be obtained in an extremely high yield, and the soundproofing for non-explosion was completed.

That is, the present invention provides an improved method for producing 0-difluorobenzene 14 in high yield by thermal decomposition in the presence of 2-70 oro-1-benzenediazonium tetrafluoroboretra silicone oil. This is what we provide.

According to the uninvented method, the desired O-difluoro-lobenzene is prepared according to the following reaction scheme, including the preparation of its starting materials.

(1) (2)
[3+As shown in the above reaction formula, 0-fluoroaniline (1) is treated in an inert aqueous solvent in the presence of a mineral acid such as hydrochloric acid, sulfuric acid, or hydrobromic acid, or in the presence of a mineral acid such as sodium nitrite. Diazotization 2 is carried out by the action of nitrate.This diazotization is usually carried out at a low temperature, for example, -30 to 20°C, preferably -15 to -5°C, for several tens of minutes to several hours. In general, nitrite is used in an amount equal to or more than the mole of compound (1), usually about 1 to 15 times the mole.After this diazotization, a fluorinating agent such as fluoroboric acid ([]BF4) is applied. Then the substitution reaction k (T becomes 2-fluoro-1-benzenediazonium tetrafluorobole 1~
(2).This fluorinating agent is added in an amount equal to or more than 7/L, usually 1 to 1.5 times.

The degree is 7'L. The 2-fluoro-]-benzenediazonium tetophfluoroborate thus obtained (2+ may be subjected to the next thermal decomposition reaction without being isolated, but it is preferable to use it after isolation. △ Yes.

2-Flu70-]-benzenediazonium tetrafluoroporate (2) is thermally decomposed into 9 violet silicone oil?
This is done by adding and heating 7]1. The silicone oil used is a well-known silicone oil, and the amount of silicone oil used is limited to 1. If the amount is too large, a small portion of the target product will be distilled out after decomposition. About 4 to 5% by weight is preferred. This non-decomposition reaction is usually carried out without a solvent at a temperature of 100 to 180°C.
x Preferably at 130-160°C for about 1-5 hours 7Jli
This is achieved by honoring oneself.

According to the uninvented method, the non-decomposition reaction proceeds very gently, the reaction vessel is relatively small and the yield rate of the target product is over 80%, which is an extremely delicious special advantage. .

Next, the non-inventive method will be explained in more detail with reference to Examples.

Example (c) No. Production of 2-fluoro-1-penzene diazonium tetrafluoroborate: Concentrated hydrochloric acid IIV (23.3 mol) was placed in a 51-volume three-day flask equipped with a thermometer, stirrer 2, and dropping funnel. ]2 and;
O-fluoroaniline 1. OK! i' (9,0 mol) ki lower. After dripping,
Stir for 30 minutes, then cool to -15°C in a circular vortex with dry ice-acetone, and add 660y of sodium nitrite (
A solution containing 9.5 mol) of 7F, l/ml was added dropwise. After the dropwise addition, the mixture was stirred for 30 minutes, and then 42% boron fluoride 7 and thread acid (f-I B F 4) 1920, /:(
The resulting precipitated crystals were washed with ice water, methanol and diethyl ether, and dried to give 1480 f/2-fluoro-1-benzenediazonium tetrafluoroporate. 78%).

(B) Manufacture of O-cyfluenthylbenzene: 2 thermometers and distillation tube (100m/valley flask attached as distillation tube,
In addition, dry Ainua seven ton traps and Na0l
-1) Place the 2-fluoro-1-benzenediazonium tetrafluorobo V-t-300F (1,4
3 mol) silicone oil 12 - Add grapes and heat on an oil bath.

Decomposition begins at 140°C, and the product is distilled out into the flask of the distillation tube. After heating at 140-150°C for 2 hours, the decomposition is completed by heating 7111+ at 160°C for 30 minutes. Collect the single product in the flask and 1-lap, wash well, and distill at normal pressure to obtain 132 g (yield 81%) of 0-difluorobenzene. Boiling point 88°C/760°C. Tomo 1zo.

Patent applicant Otsuka Pharmaceutical Co., Ltd. Representatives: Patent attorney Aohaku Ao and 1 other person

Claims (1)

[Claims] (1) 2-Fluoro-1-benzenediazonium tetoffluorene 1-? A method for producing 0-difluorobenzene, which is characterized by thermal decomposition in the presence of silicone oil.