JPH04308538A - Halogenation - Google Patents

Abstract

PURPOSE:To efficiently halogenate a primary alcohol by a mild condition such as at almost neutral pH and to selectively halogenate only the primary alcohol even in the existence of an impurity such as a secondary alcohol contained in the raw material. CONSTITUTION:In halogenation of a primary alcohol, a haloiminium salt represented by the formula (R<1> and R<2> are lower alkyl; X is halogen; (n) is 2 or 3), preferably 1,3-dimethyl-2-chloro-imidazolium chloride is used as a halogenation agent to advantageously halogenate the primary alcohol in a high yield.

Description

[Detailed description of the invention]

0001

[Industrial Field of Application] The present invention relates to a halogenation method,
More specifically, the present invention relates to a method for halogenating primary alcohols using a novel halogenating agent.

0002

BACKGROUND OF THE INVENTION Among halogen compounds, there are many compounds that are useful for introducing functional groups into molecules or as synthetic intermediates when converting one compound into another. As a method for producing this halogen compound, a method by halogenating alcohols is known, and many halogenating agents used for such halogenation have been reported, including hydrogen halides, phosphorus halides, and sulfonyl halogenides. There is.

0003

[Problems to be Solved by the Invention] However, halogenation methods using these halogenating agents generate highly corrosive hydrogen halides, so a special reaction vessel is required when implementing them on an industrial scale. Therefore, equipment such as an alkali cleaning tower had to be installed. Furthermore, since the reaction system becomes strongly acidic, it is not applicable to the halogenation of alcohols having acid-sensitive functional groups, or the yield is reduced. Furthermore, it is known that undesirable side reactions such as rearrangement reactions and dehydration reactions occur. Therefore, it has been desired to develop an industrially advantageous halogenation method that is not affected by the properties of raw alcohols and does not cause side reactions.

0004

[Means for Solving the Problems] The present inventors have been conducting intensive research on the halogenation reaction of alcohols, and have found that if a haloiminium salt represented by the following general formula (1) is used as a halogenating agent, The present invention was completed based on the discovery that the reaction can be carried out under almost neutral and mild conditions and that halogen compounds can be obtained in high yields.

That is, the present invention is a method for halogenating primary alcohols, which is characterized in that primary alcohols are reacted with a haloiminium salt represented by general formula (1) as a halogenating agent. It can be shown by the reaction formula.

[0006]

[Case 2]

[In the formula, R3 represents a primary alcohol residue, B represents a base, and R1, R2, X and n have the same meanings as above]

The haloiminium salt (1) used as a halogenating agent in the present invention is represented by the general formula (1), and in the formula (1), the lower alkyl group represented by R1 and R2 is a methyl group. , ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, and the like. Further, examples of the halogen atom represented by X include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom, and a chlorine atom is particularly preferred. Further, among the haloiminium salts (1), preferred specific examples include 2-chloro-1,3-dimethylimidazolinium chloride, 2-
Examples include chloro-1,3-dimethyl-3,4,5,6-tetrahydropyrimidinium chloride.

This haloiminium salt (1) is prepared by adding oxalyl halide, phosphorus trihalide, phosphorus pentahalide, oxyhalogen to the compound represented by the general formula (5), which is known as an easily available solvent. It can be easily obtained by reacting with a known halogenating agent such as phosphorus chloride, phosgene, trichloromethyl chloroformate, etc. In this reaction, either compound (5) or the halogenating agent is dissolved in a suitable solvent such as carbon tetrachloride,
The other is added little by little to this, and the reaction is further carried out at room temperature to 70°C for several hours to more than ten hours. The haloiminium salt (1) thus obtained can be isolated, but its reaction solution can also be used in the halogenation reaction of the present invention without isolation.

The primary alcohol (2) is not particularly limited, and may have a functional group such as an olefin, ether, ester, thiophene ring, cyano group, or ketal in its molecule. Further, in the present invention, even if a primary alcohol mixed with a secondary alcohol or a tertiary alcohol is used as a raw material, only the primary alcohol is selectively halogenated.

To carry out the present invention, 1 to 3 moles of haloiminium salt (1) and base (3) may be added to 1 mole of primary alcohol (2) and reacted at around room temperature. As the base, pyridine, triethylamine, tributylamine, etc. can be used. Although the reaction solvent does not have to be used, halogenated hydrocarbons such as dichloromethane and dichloroethane, hydrocarbons, ethers,
It is also possible to use solvents that do not participate in the reaction, such as aromatic hydrocarbons. Furthermore, even when the reaction is carried out on an industrial scale, a normal stainless steel reaction vessel can be used instead of a special reaction vessel such as a glass-lined reaction vessel. To isolate the desired halide from the reaction mixture, conventional methods such as distillation and recrystallization can be used.

0012

[Effects of the Invention] According to the method of the present invention, primary alcohols can be efficiently halogenated under almost neutral and mild conditions. Moreover, even if impurities such as secondary alcohols coexist as raw materials, only the primary alcohol can be selectively halogenated.

[0013]

EXAMPLES Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto.

Example 1 To 200 ml of dichloromethane, 24.0 ml of 1-octanol was added.
0 g and 37.4 g of 2-chloro-1,3-dimethylimidazolinium chloride were dissolved and cooled with water. 22.3 g of triethylamine was added dropwise into the mixture, and the mixture was further stirred for 12 hours. Add water to the reaction solution, separate the dichloromethane layer,
After sequentially washing with a dilute aqueous hydrochloric acid solution, a saturated aqueous sodium bicarbonate solution, and water, it was dried over anhydrous magnesium sulfate. Then, the solvent was distilled off, and the residue was distilled under reduced pressure to obtain 25.5 g of 1-chlorooctane (yield: 93.1%).

Example 2 To 200 ml of dichloromethane, 24.0 ml of 1-octanol was added.
0g and 2-chloro-1,3-dimethyl-3,4,5,
6-tetrahydropyrimidinium chloride 40.5g
was dissolved, and 22.3 g of triethylamine was added dropwise thereto to react. The reaction solution was then treated in the same manner as in Example 1 to obtain 24.8 g (yield: 90.5%) of 1-chlorooctane.

Example 3 Add 30 ml of benzyl alcohol to 200 ml of dichloromethane.
．． 0 g and 56.3 g of 2-chloro-1,3-dimethylimidazolinium chloride were dissolved, and 33.7 g of triethylamine was added dropwise thereto to react. The reaction solution was then treated in the same manner as in Example 1 to give benzyl chloride 32.
3 g (yield 92.0%) was obtained.

Example 4 9-decen-1-ol 1 was added to 50 ml of dichloromethane.
0.0 g and 13.0 g of 2-chloro-1,3-dimethylimidazolinium chloride were dissolved, and 7.8 g of triethylamine was added dropwise thereto to react. The reaction solution was then treated in the same manner as in Example 1 to obtain 11.1 g (yield: 99.0%) of 10-chloro-1-decene.

Example 5 Ethylene glycol mono-
10.0 g of β-chloroethyl ether and 2-chloro-
1,3-dimethylimidazolinium chloride 16.3
g was dissolved, and 9.7 g of triethylamine was added dropwise thereto to react. The reaction solution was then treated in the same manner as in Example 1 to obtain 10.6 g (yield: 92.2%) of bis(2-chloroethyl)ether.

Example 6 10.0 g of 1,2-hexanediol and 17.2 g of 2-chloro-1,3-dimethylimidazolinium chloride were dissolved in 50 ml of dichloromethane, and 10.3 g of triethylamine was added dropwise thereto. Made it react. The reaction solution was then treated in the same manner as in Example 1 to obtain 10.8 g (yield 93.0%) of 1-chloro-2-hexanol.

Example 7 77.0 g of 3-(3-thienyl)propanol and 110.0 g of 2-chloro-1,3-dimethylimidazolinium chloride were dissolved in 600 ml of dichloromethane, and 68.5 g of triethylamine was added dropwise thereto. And then 2 more
Stirred for 4 hours. Next, the reaction solution was treated in the same manner as in Example 1 to obtain 80.0 g of 3-(3-thienyl)propyl chloride (yield: 92.0
%) was obtained.

Example 8 In 200 ml of dichloromethane, 25.0 g of glycolic acid ethyl ester and 48.7 g of 2-chloro-1,3-dimethylimidazolinium chloride were dissolved, and 58.3 g of triethylamine was added dropwise thereto. Stir for hours. The reaction solution was then treated in the same manner as in Example 1 to obtain 26.8 g of α-chloroacetic acid ethyl ester (yield 91.0%).
I got it.

Example 9 Add 1 part of 2-cyanoethanol to 200 ml of dichloromethane.
0.0 g and 28.6 g of 2-chloro-1,3-dimethylimidazolinium chloride were dissolved, and 34.1 g of triethylamine was added dropwise thereto, followed by further stirring for 24 hours. The reaction solution was then treated in the same manner as in Example 1 to obtain 11.2 g (yield: 89.0%) of 3-chloropropionitrile.

Claims (2)

[Claims] Claim 1: The primary alcohol has the following general formula (1
) [Formula, R1 and R2 are the same or different and each represents a lower alkyl group, X represents a halogen atom, and n represents 2 or 3
1. A method for halogenating primary alcohols, which comprises reacting using a haloiminium salt represented by the following as a halogenating agent. Claim 2: The halogenating agent is 1,3-dimethyl-
The halogenation method according to claim 1, which is 2-chloro-imidazolinium chloride.