JPS6056147B2 - 3-Production method of bromphthalide - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION 3-bromphthalide is described in the literature [''Or'g, Synthesis, Vol. 23 (194
3rd year), Org, Synth, Coll, Volume
5 (1973)], both can be prepared starting from phthalide.

In the first method, phthalide is reacted with bromine, in which case hydrogen bromide and 3-bromphthalide are obtained in a yield of 8%. In the second method, phthalide is reacted with N-bromsuccinimide. 3-bromphthalide is obtained with a yield of 75-81%.

Both processes have the disadvantage that only half of the bromine used is utilized, since the other half is converted to HBr or bromide (in the case of the production of N-bromsuccinimide). The problem is to produce 3-bromphthalide in high yield and purity with relatively good utilization of bromine.

The exchange of a chloride atom for a bromide atom in organic compounds is well known in principle, and in the literature [Houben Weyl, Vol. 4/5, p. 35.4 ff], halogen exchange (Umhalogenierun)
g).

Halogen exchange is carried out by reaction of chloride with alkali metal bromides and alkaline earth metal bromides, but this reaction is often incomplete and work-up is difficult. A1Br as bromide. can also be used. Using hydrogen bromide, it is possible to exchange chloride with bromide in alkyl chlorides in the gas phase. However, the method is limited to easily volatile compounds because it requires high temperatures. Isomerization easily appears in this reaction. In acid chlorides, acid-catalyzed halogen exchange with hydrogen bromide is possible, but Staudinger
): Vol. 46, p. 1431, 1913), in this case, in order to obtain a yield of 80-85%, the amount of hydrogen bromide required by the reaction formula should be 3 to 4 times the amount used. .

Furthermore, acid-catalyzed halogenation according to the state of the art is limited to cyclic retropones, cyclic retropones and α,β-monounsaturated cyclic chloroketones. Surprisingly, it has been found that 3-chloro6.phthalide reacts with hydrogen bromide without significant decomposition or side reactions to form 3-bromphthalide.

The object of the present invention is a method for producing 3-bromphthalide from 3-chlorophthalide, which is characterized by reacting molten 3-chlorophthalide with a stoichiometric amount of 8r at 85°C or higher. The reaction is carried out at a temperature above the melting point of 3-bromphthalide (85°C), in particular from 100 to 150°C.

The released chlorine dissipates from the reaction mixture as hydrogen chloride,
It is absorbed in water in known manner, for example in a water tower. The actual quantitative utilization of the hydrogen bromide used is achieved by connecting several reactors one after the other. In the absorption stage, hydrochloric acid is obtained which is exclusively uncontaminated by aqueous hydrogen bromide. It is not absolutely necessary to use hydrogen bromide in excess. In contrast to known halogen exchanges using hydrogen bromide, according to the invention an almost quantitative exchange rate is obtained using a stoichiometric amount of HBr.
You can get it at After the reaction has ended, the reaction mixture contains almost no hydrogen bromide and 3-chlorophthalide, making work-up extremely easy. Work-up is carried out in particular by distillation.

However, it is also possible to purify 3-bromphthalide by crystallization (for example from petroleum ether or carbon tetrachloride) after the reaction has ended. According to the present invention, 3-bromphthalide can be produced in high yields of 90-96% of theory, while the previously described. According to the known state of the art, 75~
Only a yield of 81 or 83% is obtained.

Halogen exchange can be carried out without or with a catalyst.

Group ■a of the periodic table, group ■b1 ■b1■B, . Vbl
■b1■b and ■b group! Elemental halides act as catalysts to promote the reaction. Preference is given to halides or oxides of the elements b■ and especially A1 or the metals themselves. Suitable addition amounts are in the range from 0.1 to 10% by weight, in particular from 0.1 to 2% by weight, based on chlorphthalide. 3-bromphthalide can be used, for example, as a reagent for introducing a phthalidyl group into organic compounds, such as antibiotics (as described in West German Patent Publication No. 2).
No. 228255) is used.

The starting material 3-chlorphthalide is α, α, α, α, α-
Preparation of aromatic acid chlorides from aromatic acids using α,α,α,α,α-pentachloro-oxylol, which is readily available by hydrolysis of pentachloro-oxylol (see German Patent Application No. 2 622 764). It is produced as a by-product in the case of Example 1 In 84.3 parts by weight of melted 3-chlorophthalide, 10
At least 22. Dry hydrogen bromide is introduced until a weight increase to the weighing section occurs.

Vigorous stirring is advisable during this reaction, and the gas is introduced in good distribution through a glass frit to ensure complete reaction of the hydrogen bromide. After treatment by distillation, 3-bromphthalide 102 with a melting point of 69°C to
．． 4% by weight (96.1% of theory) was obtained. After recrystallization from petroleum ether, 100 parts by weight (93.9% of theory) of 3-bromphthalide with a melting point of ~85 DEG C. were obtained. Example 2 Hydrogen bromide was introduced at 100 DEG C. into three successively connected stirred vessels, each containing 843y of 3-chlorophthalide, until the calculated weight gain was reached in the first vessel.

The exhaust gas of the device was conducted through a water tower and absorbed. Work-up was carried out by distillation. 3-bromphthalide 1006
Parts by weight (94.5% of theory) were obtained.

The hydrochloric acid in the water tower had an HCl concentration of 29.8% and no bromide was detectable. Example 3 The experimental setup was the same as in Example 1.

A catalyst was added to 3-bromphthalide and the time taken to reach the theoretical weight gain was measured.

Claims (1)

[Claims] 1. A stoichiometric amount of HB in melted 3-chlorophthalide.
A method for producing 3-bromphthalide from 3-chlorophthalide, which comprises reacting r at 85°C or higher. 2 Groups IIIa, IIb, IIIb, IVb, and V of the periodic table
2. The process according to claim 1, wherein halides of elements of groups b, VIb, VIIb and VIIIb are used as catalysts.