JPS63275550A - Bromination of acetanilide and derivative thereof - Google Patents

Abstract

PURPOSE:To obtain a compound having brominated benzene ring in high yield, suppressing the bromination of side chain, by treating acetanilide or its derivative with a benzyl tri(lower alkyl)ammonium tribromide. CONSTITUTION:Acetanilide or its derivative is treated with a benzyl tri(lower alkyl)ammonium tribromide of formula in a mixed solvent (e.g. methylene chloride-methanol) preferably in the presence of a base (e.g. calcium carbonate). There is no particular restriction in the solvent, however, it is preferable to use a mixture of a halogenated alkyl solvent and an alcohol at a ratio of (1-5):1. The amount of the base is equivalent to the bromination agent. The brominated compound of acetanilide and its derivative is useful as a production raw material for various pharmaceuticals, herbicides, fungicides, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION [Object of the Invention] (Industrial Field of Application) The present invention relates to a method for brominating the benzene ring of acetanilide and its derivatives.

(Prior art and its problems) Brominated forms of acetanilide and its derivatives are useful as raw materials for the production of various medicines, herbicides, fungicides, etc.
For example, European Patent Publication No. 127.99Q)
.

Generally, bromination of an aromatic compound into a nucleus is carried out by the action of bromine in the presence of a catalyst such as a metal halide or iodine.

When acetanilide and its derivatives are brominated using these methods, unlike phenols, these compounds have reduced activity for bromination of the benzene ring, so it is not possible to efficiently obtain the desired product. ,
In some cases, by-products may be produced in which the acetyl group or nitrogen atom in the side chain is brominated.

Therefore, the present inventors conducted intensive research to improve the conventional bromination method of acetanilide, and as a result, by using benzyl tri-lower alkyl ammonium tripromide as a bromination agent, the present inventors achieved a method of brominating the side chain without brominating the side chain. The present invention was completed by discovering that the target compound in which the benzene ring was brominated could be obtained in good yield.

[Structure of the Invention] (Means for Solving the Problems) The present invention relates to a method for brominating acetanilide and its derivatives, which comprises treating acetanilide or its derivatives with benzyl tri-lower alkyl ammonium tribromide. .

The acetanilide derivative used in the present invention is not particularly limited as long as at least one position on the benzene ring is unsubstituted.Substituents for such derivatives include, for example, methyl group, ethyl group, propyl group, isopropyl group. group, butyl group, isobutyl group, 5ec-butyl group, te
Examples include alkyl groups such as rt-butyl, pentyl, and hexyl; cycloalkyl groups such as cyclohexyl; alkoxy groups such as methoxy and ethoxy; halogen atoms such as fluorine, chlorine, and bromine.

The benzyl tri-lower alkylammonium tripromide used in the present invention is represented by the following formula (1): % formula % (in the formula, R, , R2 and R3 represent the same or different lower alkyl groups) It is a compound.

In the definition of the above formula (I), the lower alkyl group is an alkyl group having 1 to 6 carbon atoms, such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, pentyl group, hexyl group, etc. Can be mentioned.

The solvent used in the present invention is not particularly limited, and has the formula (I)
Any solvent may be used as long as it dissolves the brominating agent represented by .In particular, halogenated alkyl solvents such as methylene chloride, chloroform, trichlorethylene, dichloroethylene, etc. have very high solubility and are suitable as reaction solvents. It is. Furthermore, when a lower alcohol such as methanol, ethanol, propyl alcohol, isopropyl alcohol, etc. is mixed into this solvent, the reactivity of the brominating agent increases significantly. In particular, methanol has a remarkable effect.The mixing ratio of halogenated alkyl solvent and alcohol is not particularly limited, but is usually 1:5 to 10:1, preferably 1:1 to 5.
:l.

Further, the stoichiometric amount of the brominating agent is sufficient for the substrate, and there is no need to add it in excess.

In order to further increase the reactivity, the reaction may be carried out in the presence of a base, but the base used is used for the purpose of trapping hydrogen bromide produced as a by-product after bromination. Therefore, only a slight solubility is required, and in this sense, carbonates or hydrogen carbonates of alkali metals or alkaline earth metals such as calcium carbonate, calcium hydrogen carbonate, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, etc. It is valid. It is sufficient that the amount of the base used is equivalent to that of the brominating agent CI), but even if the amount is large, the reaction will not be affected.

(Examples of the Invention) Hereinafter, the present invention will be explained in more detail with reference to Synthesis Examples and Examples, but these Examples are not intended to limit the scope of the present invention in any way.

Synthesis Example 1 Benzyltrimethylammonium tripromide (BTMABrs) (7) Synthesis of benzyltrimethylammonium chloride 1 1 , 1 g (6
0mmol) and NaBrO34.5g (30■mo
l) in 100 - of water and 18 - of hydrobromic acid (47%).
When 0 wJ was added at room temperature, crystals were immediately precipitated.

Extracted four times with 50 methylene chloride. After drying the organic layer with magnesium sulfate, the solvent was distilled off. The obtained crude crystals were recrystallized from a mixed solvent of methylene chloride/ether (10:1).

Yield Jl: 18.2g (yield 78%) m, p, 100-101"0 Synthesis Example 2 Benzyltriethylammonium tripromide (BTEABrs) + 7) Synthesis Benzyltriethylammonium chloride 13 in place of benzyl 1-trimethylammonium chloride, The same procedure as in Synthesis Example 1 was carried out using 7 g (60 mmol).

Yield: 21.3 g (yield 82%) m, p, 102-103°C Synthesis Example 3 Benzyltributylammonium tripromide (BTBABrs) (7) Synthesis Benzyltributylammonium chloride 18.7 g instead of benzyltrimethylammonium chloride (60 mmol)
The same procedure as in Synthesis Example 1 was carried out using .

Yield: 19.2g (yield 62%) m, p, 91-92°C Example 1 Synthesis of 4-bromo-2,5-xylidide 11r 2,5-xylidide o, a2g (51peng o1) and B
Put 1.95 g (5 mmol) of TMABr3 into a 504 eggplant flask, add 20 mmol of methylene chloride and 10 mmol of methanol.
- was added to the mixed solvent. After stirring at room temperature for about 1.5 hours, the solvent was distilled off. An appropriate amount of water was added to the residue, thoroughly stirred, and the liquid was removed by filtration. After washing three times with water, vacuum drying yields 1.15 g (yield 95%) of the desired title compound.
I got it. m, p, 187°C Example 2 The same procedure as in Example 1 was carried out using the raw materials shown below in place of 2,5-xylidide as the raw material for bromination of various acetanilide derivatives. The results are shown in the table.

[Effects of the Invention] According to the present invention, a nuclear brominated acetanilide derivative can be provided in good yield.

Claims (1)

[Claims] 1. A method for brominating acetanilide and its derivatives, which comprises treating acetanilide or its derivatives with benzyl tri-lower alkyl ammonium tripromide.