JPS5852231A - Synthesis of allyl chloride compound - Google Patents

Abstract

PURPOSE:To prepare allyl chloride compound easily, by reacting a terpene hydrocarbon, alcohol, alcohol ester or ether with a chlorinated isocyanuric acid which is an excellent chlorinating agent, under mild reaction conditions. CONSTITUTION:The compound of formula II is prepared by reacting a terpene hydrocarbon, alcohol, its ester or ether of formulaIwith a chlorinated isocyanuric acid at -20-50 deg.C. The chlorinated isocyanuric acid is the compound of formula III, formula IV (M is H, Na or K), etc., and its amount is excess to the raw material, i.e. 1.2-2.0 times equivalent of the raw material. Although the reaction can be carried out in the absence of a reaction solvent, however, a nonpolar solvent can be used to improve the dispersing efficiency of agitation and the operation performance of the reaction. EFFECT:There is no HCl by-production from the above chlorinating agent, and the acidification of the reaction liquid can be prevented. USE:Intermediate of a compound having polyprenyl unit in the molecule (e.g. medicine, perfume, pheromone).

Description

DETAILED DESCRIPTION OF THE INVENTION In the present invention, a special chlorinating agent, chlorinated iso-7-anuric acid, is allowed to act on a terpene compound having a terminal isopropylidene group represented by the general formula (1) R△^. This relates to a method of formulating general formula (2) in one step.

The cyclolides obtained in the present invention can be used for various compounds having polyprenyl units in the molecule, such as vitamin E, vitamins, ubiquinones, medicines such as anti-ulcer therapeutics, fragrances, and pheromones. It can be an important intermediate for manufacturing.

Conventionally, the production of compounds having polyprenyl units in these molecules Ic1l! , by chemically modifying the terminal isopropylidene group of a terpene alcohol derivative such as geraniol or linalool, which is a raw material thereof, to obtain the general formula (8) R1'l'
J X (in the formula X d-01, -on, -5o20C
Represents H-BO2◎, etc. ) has become an important problem.

For this reason, although various chemical modification methods have been announced, they are not necessarily sufficient for practical use.

For example, 1) - Synthesis of allyl alcohols by heavy ring oxygen reaction [
R, W, Dini et al., Organic, Reaction, 20 155 (1975)) 2) Synthesis of aldehydes using selenium dioxide [L, T, Aldman et al., Synthesis, 129 (197)
4)) 3) Method of adding benzene sulfuric acid/acid chloride and oxidative rearrangement [JP-A-54-921134] Evokilation with a peracid, followed by ring-opening isomerization with a base, and further halogenation, sulfone compound, etc. How to obtain [Unexamined Japanese Patent Publication No. 55-8
4908 and JP-A-54-765073 are known, but these have problems such as low anti-FJrL reaction yield, large number of steps, and disadvantages for industrial large-scale synthesis. ing.

It is known that they react equally well. (U8F4.221
,742, USF4,168,271, Japanese Patent Application Publication No. 1983-1
60527] In order to produce such useful allyl chlorides, various attempts have been made to chlorinate terpene compounds having an impropylidene group at the end, but the product is a chlorohydrin, or a combination of a chlorohydrin and an allyl chloride. However, there are few examples of selectively obtaining allyl chloride as in the present invention.

A method for producing allyl chlorides for various terpene compounds using hypochlorous acid (NOC) generated from a combination of water, 70% calcium hypochlorite, and carbon dioxide using a methylene chloride solvent. has been reported.

[Joseph, Folinsky et al., Tetrahedron, Letter 21441 (1980)] In this case, the method for generating HOCI is complicated, and the use of methylene chloride or the like as a solvent is essential, which is disadvantageous.

Also, chlorination of myrcene using chlorine has been reported.

[U8F4,221,742.1sP4,164271
] In this case, N is used to absorb and remove the by-product hydrochloric acid gas.
a. The use of COI is an essential condition. kh, Co.

If there is no existence, will it occur? Addition reactions to other double bonds in the molecule and cyclization reactions are predicted by c HCj.

That is, in methods other than those of the present invention, reaction conditions are extremely restricted.

The main features of the present invention are as follows: (1) The chlorinated incyanuric acid used as the chlorinating agent is superior to other chlorinating agents in the following points.

(1) The chlorination reaction does not involve the by-product of HOj such as chlorine, so it does not create a liquid strong acidic region, so even acid-sensitive compounds can be reacted without side reactions. .

(1) It has a stronger chlorinating ability than an organic chlorinating reagent such as N-chloro-sufushimicuimide (NC8), and can chlorinate target compounds even at room temperature.

(lit) Both the chlorinated incyanuric acid and the by-product cyanuric acid have low solubility in many organic solvents and can be easily removed from the reaction system by separating p.

Chlorinated isocyanuric acid is industrially produced in limited quantities and is easily available in the form of powder, granules, tablets, etc. with high purity, and is handled in cylinders like chlorine. It is not necessary and can be used in the same way as ordinary organic reagents.

(2) The reaction conditions are mild and the operation is easy.

Because of the above-mentioned features of chlorinated isocyanuric acid, it is very advantageous in the following points in the chlorination reaction.

(1) Reaction is possible even at room temperature or lower (1) No solvent is particularly required. However, it is possible to use an operationally advantageous amount of an inert solvent or to control the reaction rate by controlling the polarity of the solvent.

(1) For chlorination, it is sufficient to simply add chlorinated incyanuric acid to the raw material and stir while controlling the temperature.

In order to control heat generation, chlorinated incyanuric acid may be added in portions.

The chlorination method of the present invention will be described in more detail below.

First, the specific compounds of the general formula (1)R
2) Terpene alcohols such as keraniol, nerol, citronellol, and linalool (8) Alcohol esters such as geranyl acetate, neryl acetate, and farnesyl acetate (4) Alcohol ethers such as geranyl persyl ether and geranyl ethyl ether (6) Terminal Compounds and examples of the following structures having an impyroviride/group can be exemplified. (Protecting group such as zH methoxymethyl) The chlorinated isocyanuric acid that can be used in the present invention has the following structure. However, in order to complete the reaction, an excess amount of 12 to 2.0 equivalents is preferable.

Although the reaction temperature does not need to be particularly limited, it is preferably carried out at a temperature of -20 to 50°C in order to suppress excessive chlorination and decomposition of the formed nonaryl chloride.

Although a reaction solvent is not particularly required, a nonpolar solvent such as n-hexane can be used to improve the dispersion efficiency by stirring and the operability of the reaction. In addition, when chlorinating a compound with a slow reaction rate such as myrcene, it is necessary to increase the reaction rate by adding a polar solvent such as ethyl acetate.

Water-soluble solvents can also be used, but are not preferred because post-treatment becomes complicated.

After the reaction is completed, unreacted chlorinated cyanuric acid and by-product cyanuric acid are removed from the product by filtration.

The target compound can be obtained by removing residual cyanuric acid in the system by washing with water and washing with alkali, and then distilling off the solvent.

The present invention will be specifically explained below with reference to Examples, but the present invention is not limited thereto.

Example 1 Geranyl acetate 59.20 f ((L 2 mol) was converted into n-
19. Dissolve in 80 tons of hexane and maintain at -10 to 0°C, trichlorisocyanuric acid powder (Highlight 90F manufactured by Sansan Kagaku, Lichlorisocyanuric acid content 98% or more). Of ([124 eq.) was added slowly over 50 minutes.

After maintaining the temperature at -5 to 0°C for 1 hour, a small amount of the reaction solution was collected and analyzed by gas chromatography, and a small amount of unreacted geranyl acetate was detected. ! LO? (0,0
4 equivalents) of trichloroisocyanuric acid powder was added, and the mixture was further maintained at -5 to 0°C for 2 hours. In analysis by gas chromatography, no unreacted geranyl acetate was detected at the end of the reaction.

The reaction solution was filtered, and unreacted trichloroisocyanuric acid and by-product cyanuric acid were separated as white solids. Wash the white solid with n-hexane 20-, combine solution V and washing solution, wash twice with 5011It distilled water, and wash with N-sodium thiosulfate aqueous solution 50-11%) ia, co, aqueous solution 50- Each was washed once and finally washed twice with 50 d of distilled water.

Anhydrous sodium sulfate 152 was added to the resulting n-hexane solution, and the device was dried overnight.

The n-hexane was distilled off under reduced pressure, leaving 4,559 ounces of pale yellow oil.

Purity analysis by relative area method using gas chromatography showed that the target allyl chloride compound was d941%, and the yield was 85.
It was 2%.

Examples 2 to 7 The following compounds were reacted in the same manner as in Example 1, and the results are shown in Table 1. The products were analyzed by the relative area method using gas chromatography (FID detector), and for compounds with poor thermal stability, the relative area method using liquid chromatography (R-tech detector) was used. In myrcene, the distillation yield was low.

As in the example, N-chlorsfushimitsukuimide (NC
8), but as a drop, n-hexane, -
Using ethyl acid, no reaction occurred under conditions of reaction humidity of 0 to 60°C, and the raw material was only recovered.

Patent applicant: Nissan Chemical Industries, Ltd.

Claims (1)

[Claims] In the general formula (2), which is characterized in that chlorinated incyanuric acid is allowed to act on a terpene hydrocarbon, a terpene alcohol, an ester of a terpene alcohol, or a honey chill having a structure represented by the general formula (1). Method for synthesizing the allyl chlorides shown