JP2003096000A - Method for producing alkyl chloride - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for industrially and selectively producing an alkyl chloride in good yield. SOLUTION: This method for producing the alkyl chloride represented by formula (3) (wherein, R<1> and R<2> are each a group independently selected from the group consisting of alkyl groups which may have substituents, or form a cyclic alkyl group which may have a substituent by bonding to each other) comprises reacting a secondary alcohol with thionyl chloride in the presence of a catalytic amount of an N-substituted formamide.

Description

DETAILED DESCRIPTION OF THE INVENTION [0001] TECHNICAL FIELD The present invention relates to a method for producing an alkyl chloride.
On how to build. The alkyl chloride obtained in the present invention is
It is a compound useful as a raw material for medicines or liquid crystal compounds. [0002] 2. Description of the Related Art Alkyl chloride has been conventionally used instead of secondary alcohol.
The following methods are known for manufacturing
You. (1) Secondary alcohol was added to the cooled solution of phosphorus pentachloride.
Method (J. Org. Chem., Vol. 32,
2059-2063, 1967), (2) zinc chloride
The mixture of secondary alcohol and hydrochloric acid in the presence of
Method (Org. Magn. Reson., Vol. 22, 1
No. 2, pages 764 to 770, 1984), (3) second grade
Alcohol and thionyl chloride in the presence of pyridine at room temperature
(Reagents for Or)
ganic Synthesis, 1 volume, 1160-1
161 (1967), (4) Thionyl chloride and N, N
Dimethylformamide to secondary alcohols etc.
The secondary alcohol was added to the reaction mixture
Dropping method (An. Quim., Vol. 65, 163-1)
74, 1969). However, in the method (1), phosphorus pentachloride is used
Needed and produced in excess of secondary alcohol
Disposal of phosphorus-containing waste is a problem. In method (2), salt
Do not use more than equimolar amount of zinc
In order to use this method industrially, zinc chloride
Is difficult to reproduce. In the method (3), the reaction system
Gin hydrochloride is formed to form a slurry,
It is not preferable as a production method. In the method of (4), N, N-di
Requires a large amount of methylformamide,
Thionyl chloride and N, N-dimethylformamide by-produced
Must be decomposed and removed. Furthermore (1)-
In any method of (4), the desired alkyl chloride
Has low selectivity, and olefins,
Industrially effective production method to produce a large amount of
Is hard to say. [0004] SUMMARY OF THE INVENTION The object of the present invention is
A method for the selective production of alkyl with high yield is proposed.
Is to provide. [0005] DISCLOSURE OF THE INVENTION The present inventors industrially provide
Alkyl chloride using thionyl chloride which is easy to handle
As a result of intensive research on the manufacturing method,
Secondary alcohol in the presence of N-substituted formamides
Alkyl chloride is selected by reacting with thionyl chloride.
Complete the present invention by finding a method to obtain a high yield selectively
I came to. That is, the present invention provides a compound represented by the general formula (1) Embedded image (Where R¹And R²Is an alkyl which may have a substituent.
Groups independently selected from the group consisting of
Or R¹And R²Have a substituent bonded to each other
May be a cyclic alkyl group)
Of secondary alcohol and thionyl chloride in a catalytic amount
General formula (2) Embedded image (Where R³And R⁴Is from the group consisting of alkyl groups
Or an independently selected group, or R³And R⁴Is N
Can be cyclic amino groups linked together
Reaction in the presence of an N-substituted formamide
General formula (3) Embedded image (Where R¹And R²Is an alkyl which may have a substituent
Groups independently selected from the group consisting of
Or R¹And R²Are bonded to each other and have a substituent.
Which can be a cyclic alkyl group)
This is a method for producing an alkyl chloride. [0007] DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail. The present invention
In the compound of the above, an alkyl group means a group having 1 to 12 carbon atoms;
Preferably 1 to 6 linear or branched alkyl groups
Means, for example, methyl group, ethyl group, n-propyl
Group, isopropyl group, n-butyl group, isobutyl group, s
ec-butyl group, tert-butyl group, n-pentyl
Group, isopentyl group, neopentyl group, tert-pen
And a tyl group. Cyclic alkyl group refers to the number of carbon atoms
3 to 12, preferably 5 to 10 monocyclic or polycyclic
Means a cyclic alkyl group of, for example, cyclopentyl
Group, cyclohexyl group, cycloheptyl group, cyclooctyl group
And a tyl group and a decahydronaphthyl group. In addition, the above-mentioned alkyl group and cyclic alkyl group
Substituent has no effect on the reaction of the present invention.
Is not particularly limited as long as it is not, for example, an alkyl group,
Examples include an aralkyl group and an aryl group. A second class of the raw material represented by the general formula (1)
Specific examples of the alcohol include 2-propanol;
Butanol; 2-pentanol, 3-pentanol; 2
-Hexanol, 3-hexanol; 2-heptano
2-heptanol, 4-heptanol; 2-octa
2-octanol, 3-octanol, 4-octanol;
Nananol, 3-nonanol, 4-nonanol, 5-nonanol
Chain secondary alcohols such as
Pentanol, 2-methylcyclopentanol, 3-meth
Tylcyclopentanol, 2-ethylcyclopentanol
, 3-ethylcyclopentanol, 2-n-propyl
Cyclopentanol, 3-n-propylcyclopentano
, 2-isopropylcyclopentanol, 3-iso
Propylcyclopentanol, 2-n-butylcyclope
Tertanol, 3-n-butylcyclopentanol, 2-
Isobutylcyclopentanol, 3-isobutylcyclo
Pentanol, 2-sec-butylcyclopentano
, 3-sec-butylcyclopentanol, 2-te
rt-butylcyclopentanol, 3-tert-butyl
Lecyclopentanol; cyclohexanol, 2-methyl
Lecyclohexanol, 3-methylcyclohexanol
, 4-methylcyclohexanol, 2-ethylcyclo
Hexanol, 3-ethylcyclohexanol, 4-E
Tylcyclohexanol, 2-n-propylcyclohexyl
Sanol, 3-n-propylcyclohexanol, 4-
n-propylcyclohexanol, 2-isopropyl
Clohexanol, 3-isopropylcyclohexanol
4-isopropylcyclohexanol, 2-n-butyl
Tylcyclohexanol, 3-n-butylcyclohexa
, 4-n-butylcyclohexanol, 2-iso
Butylcyclohexanol, 3-isobutylcyclohexyl
Sanol, 4-isobutylcyclohexanol, 2-s
ec-butylcyclohexanol, 3-sec-butyl
Cyclohexanol, 4-sec-butylcyclohexa
, 2-tert-butylcyclohexanol, 3
-Tert-butylcyclohexanol, 4-tert
-Butylcyclohexanol; cycloheptanol, 2
-Methylcycloheptanol, 3-methylcyclohepta
Nol, 4-methylcycloheptanol, 2-ethyl
Cloheptanol, 3-ethylcycloheptanol, 4
-Ethylcycloheptanol, 2-n-propylcyclo
Heptanol, 3-n-propylcycloheptanol,
4-n-propylcycloheptanol, 2-isopropyl
Lecycloheptanol, 3-isopropylcyclohepta
Nord, 4-isopropylcycloheptanol, 2-n
-Butylcycloheptanol, 3-n-butylcyclohexane
Butanol, 4-n-butylcycloheptanol, 2-
Isobutylcycloheptanol, 3-isobutylcyclo
Heptanol, 4-isobutylcycloheptanol, 2
-Sec-butylcycloheptanol, 3-sec-butyl
Tylcycloheptanol, 4-sec-butylcyclohexane
Butanol, 2-tert-butylcycloheptano
3-tert-butylcycloheptanol, 4-t
tert-butylcycloheptanol; cyclooctano
, 2-methylcyclooctanol, 3-methylcyclo
Octanol, 4-methylcyclooctanol, 5-meth
Tylcyclooctanol, 2-ethylcyclooctanol
, 3-ethylcyclooctanol, 4-ethylcyclo
Octanol, 5-ethylcyclooctanol, 2-n
-Propylcyclooctanol, 3-n-propylcycl
Looctanol, 4-n-propylcyclooctano
, 5-n-propylcyclooctanol, 2-isoprop
Ropylcyclooctanol, 3-isopropylcycloo
Kutanol, 4-isopropylcyclooctanol, 5
-Isopropylcyclooctanol, 2-n-butyloxy
Crooctanol, 3-n-butylcyclooctano
, 4-n-butylcyclooctanol, 5-n-butyl
Lecyclooctanol, 2-isobutylcyclooctano
, 3-isobutylcyclooctanol, 4-isobu
Tylcyclooctanol, 5-isobutylcycloocta
Nol, 2-sec-butylcyclooctanol, 3-
sec-butylcyclooctanol, 4-sec-butyl
Lecyclooctanol, 5-sec-butylcyclooctane
Tanol, 2-tert-butylcyclooctanol,
3-tert-butylcyclooctanol, 4-ter
t-butylcyclooctanol, 5-tert-butyl
Cyclooctanol; decahydro-1-naphthol, de
Cyclic secondary alcohols such as cahydro-2-naphthol
But not limited thereto. The N-substituted phor represented by the general formula (2)
Muamide is R³And R⁴Are the same or different alkyl groups
N, N-dialkyl-substituted formamide which is³
And R ⁴Are composed together of a divalent carbon chain (eg,
-C₅H₁₀−) And adjacent nitrogen atoms together form
Formyl group is substituted for the so-called cyclic amine
N-formyl cyclic amine, and specific examples thereof include:
N, N-dimethylformamide (hereinafter abbreviated as DMF),
N, N-diethylformamide, N, N-diisopropyl
Ruformamide, N, N-dibutylformamide, 1-
But not limited to formylpiperidine
It is not done. The salification of the target compound represented by the general formula (3)
Specific examples of alkyl include 2-chloropropane;
Chlorobutane; 2-chloropentane, 3-chloropentane
2-chlorohexane, 3-chlorohexane; 2-k
Loloheptane, 3-chloroheptane, 4-chlorohepta
2-chlorooctane, 3-chlorooctane, 4-k
Lorooctane; 2-chlorononane, 3-chlorononane,
Chain-like salification such as 4-chlorononane and 5-chlorononane
Alkyl is chlorocyclopentane, 1-chloro
-2-methylcyclopentane, 1-chloro-3-methyl
Cyclopentane, 1-chloro-2-ethylcyclopenta
1-chloro-3-ethylcyclopentane, 1-chloro
B-2-n-propylcyclopentane, 1-chloro-3
-N-propylcyclopentane, 1-chloro-2-iso
Propylcyclopentane, 1-chloro-3-isopropyl
Lecyclopentane, 1-chloro-2-n-butylcyclo
Pentane, 1-chloro-3-n-butylcyclopenta
1-chloro-2-isobutylcyclopentane, 1-
Chloro-3-isobutylcyclopentane, 1-chloro-
2-sec-butylcyclopentane, 1-chloro-3-
sec-butylcyclopentane, 1-chloro-2-te
rt-butylcyclopentane, 1-chloro-3-ter
t-butylcyclopentane; chlorocyclohexane, 1
-Chloro-2-methylcyclohexane, 1-chloro-3
-Methylcyclohexane, 1-chloro-4-methylcyclyl
Hexane, 1-chloro-2-ethylcyclohexane,
1-chloro-3-ethylcyclohexane, 1-chloro-
4-ethylcyclohexane, 1-chloro-2-n-pro
Pyrcyclohexane, 1-chloro-3-n-propyl
Chlohexane, 1-chloro-4-n-propylcyclohexane
Xane, 1-chloro-2-isopropylcyclohexa
1-chloro-3-isopropylcyclohexane, 1
-Chloro-4-isopropylcyclohexane, 1-chloro
B-2-n-butylcyclohexane, 1-chloro-3-
n-butylcyclohexane, 1-chloro-4-n-butyi
Rucyclohexane, 1-chloro-2-isobutylcyclo
Hexane, 1-chloro-3-isobutylcyclohexa
1-chloro-4-isobutylcyclohexane, 1-
Chloro-2-sec-butylcyclohexane, 1-chloro
B-3-sec-butylcyclohexane, 1-chloro-
4-sec-butylcyclohexane, 1-chloro-2-
tert-butylcyclohexane, 1-chloro-3-t
tert-butylcyclohexane, 1-chloro-4-te
rt-butylcyclohexane; chlorocycloheptane,
1-chloro-2-methylcycloheptane, 1-chloro-
3-methylcycloheptane, 1-chloro-4-methylsi
Cloheptane, 1-chloro-2-ethylcyclohepta
1-chloro-3-ethylcycloheptane, 1-chloro
B-4-ethylcycloheptane, 1-chloro-2-n-
Propylcycloheptane, 1-chloro-3-n-propyl
Lecycloheptane, 1-chloro-4-n-propylcycl
Loheptane, 1-chloro-2-isopropylcyclohep
Tan, 1-chloro-3-isopropylcycloheptane,
1-chloro-4-isopropylcycloheptane, 1-c
Loro-2-n-butylcycloheptane, 1-chloro-3
-N-butylcycloheptane, 1-chloro-4-n-bu
Tylcycloheptane, 1-chloro-2-isobutylcyclyl
Roheptane, 1-chloro-3-isobutylcyclohepta
1-chloro-4-isobutylcycloheptane, 1-
Chloro-2-sec-butylcycloheptane, 1-chloro
B-3-sec-butylcycloheptane, 1-chloro-
4-sec-butylcycloheptane, 1-chloro-2-
tert-butylcycloheptane, 1-chloro-3-t
tert-butylcycloheptane, 1-chloro-4-te
rt-butylcycloheptane; chlorocyclooctane,
1-chloro-2-methylcyclooctane, 1-chloro-
3-methylcyclooctane, 1-chloro-4-methylsi
Crooctane, 1-chloro-5-methylcycloocta
1-chloro-2-ethylcyclooctane, 1-chloro
B-3-ethylcyclooctane, 1-chloro-4-ethyl
Lecyclooctane, 1-chloro-5-ethylcyclooctane
Tan, 1-chloro-2-n-propylcyclooctane,
1-chloro-3-n-propylcyclooctane, 1-c
Loro-4-n-propylcyclooctane, 1-chloro-
5-n-propylcyclooctane, 1-chloro-2-i
Sopropylcyclooctane, 1-chloro-3-isopro
Pyrcyclooctane, 1-chloro-4-isopropyl
Crooctane, 1-chloro-5-isopropylcycloo
Butane, 1-chloro-2-n-butylcyclooctane,
1-chloro-3-n-butylcyclooctane, 1-chloro
B-4-n-butylcyclooctane, 1-chloro-5-
n-butylcyclooctane, 1-chloro-2-isobutyi
Rucyclooctane, 1-chloro-3-isobutylcyclo
Octane, 1-chloro-4-isobutylcycloocta
1-chloro-5-isobutylcyclooctane, 1-
Chloro-2-sec-butylcyclooctane, 1-chloro
B-3-sec-butylcyclooctane, 1-chloro-
4-sec-butylcyclooctane, 1-chloro-5-
sec-butylcyclooctane, 1-chloro-2-te
rt-butylcyclooctane, 1-chloro-3-ter
t-butylcyclooctane, 1-chloro-4-tert
-Butylcyclooctane, 1-chloro-5-tert-
Butylcyclooctane; 1-chlorodecahydronaphthale
, Cyclic chlorination such as 2-chlorodecahydronaphthalene
Including but not limited to alkyl
Absent. For the reaction between a secondary alcohol and thionyl chloride
The production of alkyl chlorides by
Performed in the presence of a mid. Here, the amount of catalyst refers to the secondary
0.003 to 0.10 in molar ratio to alcohol,
Preferably 0.005 to 0.05, more preferably
It means 0.009 to 0.02. Molar ratio is 0.00
If it is less than 3, no catalytic effect is observed,
If more than 10, thionyl chloride and N-substituted formaldehyde
Post-treatment such as the generation of a large amount of by-products consisting of amide salts
Not only is it complicated, but the yield also decreases. The amount of thionyl chloride used is a secondary alcohol
It is sufficient if it is at least equimolar to
It is 1.3 times mol. The solvent used has an adverse effect on the reaction.
So that raw materials such as secondary alcohols are sufficiently dissolved.
There is no particular limitation as long as it is appropriate. As a specific example,
Aliphatic hydrocarbons such as sun, heptane and octane;
Hexane, cycloheptane, methylcyclohexane, etc.
Alicyclic hydrocarbons; benzene, toluene, xylene, etc.
And the like. Mixed solvent
It may be. Preferred solvents depending on the reaction raw materials, etc.
Different, for example, for cycloalkanols
Cyclic hydrocarbon solvents are preferred. [0015] The reaction temperature depends on the solvent used.
However, the temperature is preferably 70 to 145 ° C., preferably the reflux temperature.
Degrees. If the temperature is lower than the reflux temperature, the yield of the desired product decreases. The reaction time depends on the solvent, the reaction temperature and the target substance.
But usually between 2 and 12 hours. [0017] The present invention will be further described below with reference to Examples and Comparative Examples.
Although described, the present invention is not limited thereby.
No. Embodiment 1 Condenser, exhaust pipe, stirrer, thermometer, 10 ml side pipe
100 ml three-necked flask equipped with a dropping funnel
-Tert-butylcyclohexanol 10 g (63.
9mmol), DMF 0.0467g (0.6mmo
l), charged with 50 g of methylcyclohexane,
Start heating in an oil bath set at 140 ° C below,
The mixture was heated to reflux at 104 ° C. After confirming the start of reflux, in the flask
While maintaining the temperature at 100 ° C. or higher, 8.4 g of thionyl chloride (7
0.6 mmol) from the dropping funnel in 2 hours 20 minutes
did. After completion of the dropwise addition, the mixture was heated and refluxed for another 1 hour to react. Room
After cooling to temperature, the reaction mixture was separated by gas chromatography.
When analyzed, 1-chloro-4-tert-butyl cycle
The yield of rohexane was 77.6%. Embodiment 2 Condenser, exhaust pipe, stirrer, thermometer, 10 ml side pipe
100 ml three-necked flask equipped with a dropping funnel
10 g of ethylcyclohexanol (77.9 mmol
l), 0.0563 g (0.77 mmol) of DMF,
34 g of tylcyclohexane was charged, and 13
Start heating in an oil bath set at 0 ° C,
And heated to reflux. After confirming the start of reflux, the internal temperature of the flask was reduced to 10
While maintaining the temperature at 0 ° C. or higher, 10.2 g of thionyl chloride (85.8) was used.
mmol) was dropped from the dropping funnel in 50 minutes. Dripping
After the completion, the mixture was heated under reflux for another 2 hours to react. Cool to room temperature
After that, the reaction mixture was analyzed by gas chromatography.
The yield of 1-chloro-4-ethylcyclohexane was 6
7.9%. Embodiment 3 Condenser, exhaust pipe, stirrer, thermometer, drop with side pipe
Decahydro-2- in a 5 L four-necked flask equipped with a funnel
Naphthol 655 g (4.25 mol), DMF 3 g
(0.041 mol), methylcyclohexane 1530
g, and start heating with a mantle heater under a nitrogen stream.
And heated to 104 ° C. under reflux. After confirming the start of reflux,
While maintaining the inside temperature of the
550 g thionyl chloride (4.62) diluted with 830 g
mol) was dropped from the dropping funnel in 8 hours and 10 minutes. drop
After the lower end, the mixture was further heated under reflux for 3 hours to react. Cool to room temperature
After the reaction, the reaction mixture was analyzed by gas chromatography.
At this time, the yield of 2-chlorodecahydronaphthalene was 58.
2%. Embodiment 4 Condenser, exhaust pipe, stirrer, thermometer, 10 ml side pipe
Into a 30 ml three-necked flask equipped with a dropping funnel
Looctanol 2 g (15.6 mmol), DMF 0.
0113 g (0.16 mmol), methylcyclohexa
6 g, and set at 140 ° C. under a nitrogen stream.
Heating was started in an ir bath, and the mixture was heated and refluxed at 106 ° C. Return
After confirming the start of flow, keep the temperature inside the flask at 100 ° C or higher.
2.03 g (17.14 mmol) of thionyl chloride was added dropwise.
It was dropped from the funnel in 20 minutes. 3 o'clock after dropping
The mixture was heated under reflux for a reaction. After cooling to room temperature, the reaction mixture is
When analyzed by chromatography, chlorocyclo
Octane yield was 75.6%. Embodiment 5 Condenser, exhaust pipe, stirrer, thermometer, 10 ml side pipe
Into a 30 ml three-necked flask equipped with a dropping funnel
Heptanol 2 g (17.2 mmol), DMF 0.0
125 g (0.17 mmol), 6 g of heptane
Start heating in an oil bath under a stream of nitrogen.
And heated to reflux. After confirming the start of reflux, the internal temperature of the flask was set to 95
2.24 g of thionyl chloride (18.93
mmol) was added dropwise from the dropping funnel over 25 minutes. Dripping
After the completion of the reaction, the mixture was further heated under reflux for 3 hours to react. Cool to room temperature
After that, the reaction mixture was analyzed by gas chromatography.
The yield of 4-chloroheptane was 62.0%. Embodiment 6 Condenser, exhaust pipe, stirrer, thermometer, 10 ml side pipe
In a 30 ml three-necked flask equipped with a dropping funnel
2.2 g (17.2 mmol) of octanol, DMF
0.0125 g (0.17 mmol), 6 g of octane
Charge, start heating in an oil bath under a nitrogen stream, 13
The mixture was heated to reflux at 0 ° C. After confirming the start of reflux, adjust the temperature inside the flask.
2.24 g of thionyl chloride (1
8.93 mmol) from the dropping funnel in 25 minutes.
Was. After completion of the dropwise addition, the mixture was further heated under reflux for 3 hours to react. room temperature
After cooling down, analyze the reaction mixture by gas chromatography
As a result, the yield of 3-chlorooctane was 60.0%.
there were. Embodiment 7 Condenser, exhaust pipe, stirrer, thermometer, 15 ml side pipe
100 ml three-necked flask equipped with a dropping funnel
-10 g of methylcyclohexanol (87.6 mmol
l), 1-formylpiperidine 0.099 g (0.87
mmol) and 45 g of methylcyclohexane.
Open heating in an oil bath set at 130 ° C under airflow
And heated to 105 ° C. under reflux. After confirming the start of reflux,
10. Thionyl chloride while maintaining the temperature inside the flask at 100 ° C. or higher
4 g (95.9 mmol) from the dropping funnel for 3 hours 45
Dropped in minutes. After completion of the dropwise addition, the mixture is further heated under reflux for 2 hours for
did. After cooling to room temperature, the reaction mixture was subjected to gas chromatography.
Analysis by 1-chloro-4-methylcyclo
Hexane yield was 74.8%. Embodiment 8 Condenser, exhaust pipe, stirrer, thermometer, 15 ml side pipe
100 ml three-necked flask equipped with a dropping funnel
-10 g of methylcyclohexanol (87.6 mmol
l), N, N-diisopropylformamide 0.113
g (0.87 mmol), 45 g of methylcyclohexane
And set at 130 ° C under a nitrogen stream.
Then, the mixture was heated at 105 ° C. and refluxed. Start reflux
After confirmation, the temperature in the flask was maintained at
11.4 g (95.9 mmol) of onil was added dropwise.
2 hours and 20 minutes. Add 2 hours after dropping
The mixture was heated under reflux to react. After cooling to room temperature, the reaction mixture is
When analyzed by chromatography, 1-chloro-4-
The yield of methylcyclohexane was 69.4%. Embodiment 9 Condenser, exhaust pipe, stirrer, thermometer, 15 ml side pipe
100 ml three-necked flask equipped with a dropping funnel
-10 g of methylcyclohexanol (87.6 mmol
l), DMF 0.064 g (0.87 mmol),
45 g of hexane, and set to 130 ° C under a nitrogen stream.
Start heating in a hot oil bath and reflux at 85 ° C
did. After confirming the start of reflux, keep the temperature inside the flask at 80 ° C or higher.
11.4 g (95.9 mmol) of thionyl chloride
The solution was dropped from the dropping funnel in 3 hours. 2 more after dropping
The mixture was heated under reflux for an hour to react. After cooling to room temperature,
When analyzed by chromatography, 1-chloro
The yield of -4-methylcyclohexane was 67.7%.
Was. Embodiment 10 Condenser, exhaust pipe, stirrer, thermometer, 10 ml side pipe
In a 20 ml three-necked flask equipped with a dropping funnel
2 g (17.5 mmol) of methylcyclohexanol,
0.0128 g (0.175 mmol) of DMF, tolue
7.6 g, and set at 140 ° C. under a nitrogen stream.
Start heating in a heated oil bath and heat to reflux at 111 ° C.
Was. After confirming the start of reflux, keep the temperature inside the flask at 100 ° C or higher.
2.3 g (19.26 mmol) of thionyl chloride
The solution was dropped from the dropping funnel in 45 minutes. After dropping,
The mixture was reacted by heating under reflux for 30 minutes. After cooling to room temperature,
Was analyzed by gas chromatography.
The yield of loro-4-methylcyclohexane was 48.9%.
there were. Embodiment 11 Condenser, exhaust pipe, stirrer, thermometer, 30 ml side pipe
Into a 200 ml four-necked flask equipped with a dropping funnel
-Methylcyclohexanol 20 g (175.1 mmol
l), DMF 0.13 g (1.77 mmol), methyl
67.5 g of cyclohexane was charged, and 14
Start heating in an oil bath set at 0 ° C,
And heated to reflux. After confirming the start of reflux, the internal temperature of the flask was reduced to 10
While maintaining the temperature at 0 ° C. or higher, 22.8 g of thionyl chloride (191.
6 mmol) from the dropping funnel in 4 hours and 30 minutes.
Was. After completion of the dropwise addition, the mixture was heated and refluxed for another 2 hours to react. room temperature
After cooling down, analyze the reaction mixture by gas chromatography
As a result, 1-chloro-3-methylcyclohexane
The yield was 66.9%. Embodiment 12 Condenser, exhaust pipe, stirrer, thermometer, 10 ml side pipe
Into a 30 ml three-necked flask equipped with a dropping funnel
2 g (17.5 mmol) of methylcyclohexanol,
The amounts of DMF and methylcyclohexane 6 g shown in Table 1 were prepared.
In an oil bath set at 140 ° C under a nitrogen stream.
Heating was started and the mixture was refluxed at 105 ° C. Confirm reflux start
Then, while maintaining the temperature inside the flask at 100 ° C or higher,
2.3 g (19.3 mmol) from a dropping funnel to 75 g
In minutes. After the completion of the dropwise addition, the mixture was refluxed for 3 hours.
I responded. After cooling to room temperature, the reaction mixture is subjected to gas chromatography.
And the desired product, 1-chloro-4-methylcyclyl
Rohexane and the transfer product, 1-chloro-3-methylcyclo
The hexane yield was measured. The results are shown in Table 1.
You. [0030] [Table 1] From this table, the rationality of the essential requirements of the present invention and the secondary
The preferred range of the number of moles of DMF to coal is 0.00
3 to 0.10 times, preferably 0.005 to 0.05 times,
More preferably, it is 0.009 to 0.02 times.
I understand. [0031] According to the present invention, a drug or a liquid crystal compound
Alkyl chloride, which is useful as a raw material
It can be manufactured selectively.

   ────────────────────────────────────────────────── ─── Continuation of front page    (72) Inventor Teruji Onoki             No. 1-1 Muramachi, Takatsuki-shi, Osaka Japan Tobacco Production             Pharmaceutical Research Institute, Inc. F-term (reference) 4H006 AA02 AC13 AC30 BA51 BE51                       EA02 EA12                 4H039 CA52 CD30

Claims (1)

[Claim 1] The general formula (1) (Wherein, R ¹ and R ² are each independently selected from the group consisting of alkyl groups which may have a substituent, or R ¹ and R ² are bonded to each other to form a substituent And a thionyl chloride represented by the general formula (2) in a catalytic amount: Wherein R ³ and R ⁴ are each independently selected from the group consisting of alkyl groups, or R ³ and R ⁴ can be cyclic amino groups bonded together with N. Wherein the reaction is carried out in the presence of an N-substituted formamide represented by the following general formula (3): (Wherein, R ¹ and R ² are each independently selected from the group consisting of alkyl groups which may have a substituent, or R ¹ and R ² are bonded to each other to form a substituent Which may be a cyclic alkyl group which may be present).