JPH0272140A - Optically active carboxylic acid esters and production thereof - Google Patents

Abstract

NEW MATERIAL:An optically active carboxylic ester shown by formula I (R is <=2C alkyl or >=2C alkenyl; m is 1; * is asymmetric carbon). EXAMPLE:(+)-4'-(1-Hydroxyethyl)biphenylcarboxylic acid octyl ester. USE:An intermediate for a ferroelectric liquid crystal compound. PREPARATION:A carboxylic acid shown by formula II is reacted with an alkylating agent shown by formula III [R' is alkyl, alkenyl or aralkyl (may be replaced with alkyl, alkoxy or halogen); X is halogen, or -OSO2R''' (R''' is alkyl or phenyl which may be replaced)] in the presence of a basic substance to give an optically active carboxylic ester shown by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Applications> The present invention relates to optically active carboxylic acid esters useful as intermediates for organic single-child materials such as liquid crystal compounds.

<Conventional technology> Conventionally, formula (In the formula, R' represents a methyl group, and l is 1.

The optically active carboxylic acid ester indicated by * indicates an asymmetric carbon atom, ) is a known compound (Mona
tshefte far Chemie 116.

1288-1286, 1985), and such compounds were produced by the method shown below.

Hs (In the formula, R', l and main mouth have the same meanings as above.

) However, the general formula (lV)7F(8 ROOC-+Q-)--CH-OH(ff)m (wherein, R represents an alkyl group or alkenyl group having 2 or more carbon atoms, and m is As far as the present inventors know, the optically active carboxylic acid esters represented by (1) are asymmetric carbon atoms, and are novel compounds that have not been described in any literature. Nothing is known about its usefulness as a compound, let alone its production method.

As mentioned above, no industrially advantageous method for producing optically active carboxylic acid esters corresponding to the optically active carboxylic acid ester (methyl ester Jl/) represented by the above formula is known.

<Problems to be Solved by the Invention> The present invention provides optically active carboxylic acid esters useful as intermediates for novel ferroelectric liquid crystal compounds and a method for producing the same.

Means for Solving the Problems> That is, the present invention provides optically active carboxylic acid esters represented by the general formula (ff) and general formula (1) (where n is 1 or 2.* (The mark indicates an asymmetric carbon atom.) In the presence of a basic substance, carboxylic acids represented by the general formula (1) % formula % () (where R' is an alkyl group, an alkenyl group or lower alkyl, lower alkoxy, or an aralkyl group optionally substituted with a halogen atom.X represents a halogen atom or 105O2R.Here, R represents a lower alkyl group or an optionally substituted phenyl group of optically active carboxylic acid esters represented by the general formula (1) (wherein R, n and * marks are the same as above), which are reacted with an alkylating agent represented by This is the manufacturing method.

The present invention will be explained in detail below. In the alkylation reaction to obtain the optically active carboxylic acid ester represented by the general formula (1), the basic substances used include, for example, alkali metal carbonates such as sodium carbonate, potassium carbonate, and calcium carbonate; Inorganic bases and alkali metals that give earth metals, alkali or alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, alkali metal alcohols such as sodium ethylate, sodium methylate, etc. Alcolade, and even triethylamide X1.
Examples include organic amines such as 8-diazabicyclo[5,4,0')-7-undecene (hereinafter referred to as DBU) and n-)butylamine.

The amount of such a basic substance is required to be at least 1 equivalent to the carboxylic acid (1), but in the case of an inorganic base and an alkali metal alcoholade that provide carboxylic acid metal salts, it is usually 1 equivalent to the carboxylic acid (1).
~1.2 times the equivalent, and in the case of organic amines, 1 to 8 times the equivalent is sufficient. In addition, if the formation of carboxylic acid metal salt is insufficient due to the type 4 solvent, a large excess amount may be used.

In this alkylation reaction, it is preferable to use a promoter, which is effective in terms of reaction rate and yield.

Examples of such promoters include phase transfer promoters such as tetrabutylammonium bromide, chloride, hydroxide, trimethylbenzylammonium chloride, cetyltrimethylammonium chloride, polyoxyethylene glycols, alkylphosphonium salts, and decylbenzenesulfonate. A catalyst is exemplified, and the amount of the co-catalyst used is 0.001 times to 0.5 times the weight of the carboxylic acid (1).

Here, examples of the alkylating agent represented by the general formula (1) include the following compounds.

Ethyl bromide, propyl bromide, isopropyl bromide, propyl iodide, butyl bromide, isobutyl bromide, pentyl chloride, pentyl bromide, isopentyl bromide, pentyl iodide, 2-methylbutyl bromide, hexyl bromide, hexyl iodide , heptyl bromide, octyl bromide, 2-methylhebutyl bromide, nonyl bromide, decyl bromide, dodecyl bromide, pentadecyl bromide, allyl chloride, allyl bromide, 8-butynyl bromide, 2-pentenyl bromide, 8-hexenyl bromide, benzyl bromide Mido, methoxybenzyl chloride, methylbenzyl bromide, chlorobenzyl chloride, bromobenzyl bromide, phenethyl bromide, phenylpropyl bromide, phenylbutyl bromide, propyl tosylate, butyl tosylate, isobutyl tosylate, hexyl tosylate, Heptyl tosylate, octyl tosylate, decyl tosylate, dodecyl tosylate, octadecyl tosylate, phenylpropyl tosylate, phenyl butyl tosylate, butyl methanesulfonate, hexyl methanesulfonate, octyl methanesulfonate, phenylbutyl methanesulfonate (alkyl Of the oxidizing agents, R
is a branched alkyl group, R-X may be an optically active purkylating agent).

The amount of such alkylating agent ■ used is the same as that of carboxylic acids (
The amount is required to be 1 equivalent or more, but usually 5 equivalents or less, preferably 1 to 8 times the amount. Further, the other raw material, carboxylic acids ([), can be produced as follows.

CHa COg. Br-1 → CHB C around two 3. −
CN〒H8 11 → CH8COO-CH-(-Q+, -COOCH8
H8 CH3COO-CH-+O cuff C00CHs* (In the formula, n and country of origin have the same meanings as above.) Examples of the reaction solvent include the following.

Water, methanol, ethanol, propatool, acetone, methyl ethyl ketone, chlorobenzene, toluene, xylene, hexane, heptane, ethyl ether, tetrahydrofuran, dioxane, dimethylformamide, N
- Solvents inert to the reaction of aliphatic or aromatic hydrocarbons such as methylpyrrolidone, ethers, alcohols, ketones, amides, and halogenated hydrocarbons are used alone or in mixtures, and the amount used is not particularly limited. .

Moreover, polar solvents such as dimethyl sulfoxide and hexamethylphosphorylamide can also be used.

The reaction temperature is usually -20"C to 120C, preferably O"C to 100"C.

The reaction time is not particularly limited. After the reaction is completed, optically active carboxylic acid esters can be obtained in good yield by conventional separation means such as extraction, separation, concentration, recrystallization, etc., which can be further purified by column chromatography etc. if necessary. Achievement (Effect of the Invention) Thus, according to the method of the present invention, the optically active carboxylic acid ester represented by the general formula (1) can be produced with industrial advantage.

Furthermore, the compound represented by the general formula (2) can be obtained without any novel optical activity, and the compound has very excellent properties as a strong 8W liquid crystal.

CH.

(In the above formula, R1 and R2 represent an alkyl group, p
is 1 or 2. R, m and home country are the same as above. ) Furthermore, novel optically active carboxylic acid esters (Iv
) can also be used as an intermediate for agricultural chemicals, medicines, etc.

<Example> The present invention will be explained below with reference to Examples.

Example 1 Into a 4-hour flask equipped with a stirrer and a thermometer, (T)
-4-(1-hydroxyethyl)biphenylcarboxylic acid 1.21 g (5 mmol), octyl bromide 1.54
F (8 mmol), 1,8-diazabicyclo(5,4,
0)-7-undecene (DBU) 0.91F (6 mmol), toluene 10- and dimethylformamide 5-
and stirred at 80-40'0 for 20 hours. After the reaction is completed, 2° of toluene is added to the reaction solution, which is then washed successively with water, 2% hydrochloric acid, and water. After drying the organic layer over magnesium sulfate, the solvent was distilled off. The residue is purified by column chromatography using chloroform. Octyl (t)-4-(1-hydroxyethyl)biphenylcarboxylate 1.67F (yield 94.5%) was obtained.

[α], +21.0''' (c=1, CHCl1a)
, melting point 70-71'C Example 2 Into the same apparatus as in Example 1, 0.88 F (5 mmol) of cyclo-4-(1-hydroxyethyl)benzoic acid, 1.28 N (10 mmol) of propyl bromide, DBUo, 919
(6 mmol) and toluene, 80
Stir at ~40°C for 20 hours. After the reaction is completed, the reaction solution is washed successively with water, 2% hydrochloric acid, and water.

After drying the organic layer over magnesium sulfate, the solvent was distilled off. Purify the residue by column chromatography using chloroform.
Propyl 3-4-(1-hydroxyethyl)benzoate 0
．． 97N (yield 98.5%) was obtained.

Cα]o +86.2' (c = 1, CHCl
m)n DL-5286 Example 8 Into the same apparatus as in Example 1, 1.211! of (t)-4-(1-hydroxyethyl)biphenylcarboxylic acid! (5 mmol), benzyl bromide 1.87N (8 mmol),
0.121 of tetrabutylammonium bromide, 0.219 (5.25 mmol) of caustic soda, 8 of water and 10 of toluene are charged and stirred at 60-70°C for 10 hours. After the reaction, the organic layer was separated and mixed with water, 2% hydrochloric acid,
Wash sequentially with water. Thereafter, post-treatment and purification were carried out according to Example 1. (t)-4'-(1-hydroxyethyl)
Benzyl biphenylcarboxylate 1.88F (yield 80%)
) was obtained.

[α]. +25.8° (c = 1, CHCl!
8), melting point 106-108°C Example 4 (→-4-(1-hydroxyethyl)benzoic acid 0.88 f (5Z) The reaction, post-treatment, and purification were carried out in the same manner as in Example 8, except for using J mole).

Benzyl H-4-(1-hydroxyethyl)benzoate 1
．． Og (yield 78%) is obtained.

[α) +a4.6° (c = 1, CHCl
,)n, 1.5694 Example 5 Into a 4-hour flask equipped with a stirrer and a thermometer, ←)-
4'-(1-hydroxyethyl)biphenylcarbon f
jl 1.21 II (5E Rimol), pentyl bromide 1.51f (IOE Rimol), 1,8-diazabicyclo(5,4,0]-7-undecene (DBU) o, 9
Add tp (s mmol) and 10-tetrahydrofuran and stir at 80-40°C for 15 hours. After the reaction is completed, 20- toluene is added to the reaction solution, and then washed sequentially with water, 2% hydrochloric acid, and water. After drying the organic layer over magnesium sulfate, the solvent was distilled off.

The residue is purified by column chromatography using chloroform. f-
1.42f (ItS 191%) of pentyl 1-4'-(1-hydroxyethyl)biphenylcarboxylate was obtained.

[α], -25.5° (c=1, CHCl8),
Melting point: 69-71°C Example 6 In place of (e)-4'-(1-hydroxyethyl)biphenylcarboxylic acid, 0.88N (5 mmol) of f-1-4-(1-1=droxyethyl)benzoic acid ), p-methylbenzyl tosylate 2.7 instead of benzyl bromide
The reaction, post-treatment and purification were carried out in accordance with Example 8 except that 6F (0.01 mol) was used. ←)-4-(1-hydroxyethyl) p-methylbenzyl benzoate 1.09f(
Yield: 81%).

[α]D -88-0' (c = 1, CHCl1
a), nDl, 5682 Examples 7 to 11 The reaction, post-treatment, and
It was purified and the results shown in Table 1 were obtained.

(Left below) Also, if (←)-4-(1-hydroxyethyl)benzoic acid is used as the raw material compound instead of (-1-3-4-(1-hydroxyethyl)benzoic acid), the same as the above example is used. If phenylpropyl bromide or hexenyl bromide is used as the alkylating agent (1) in
-Hydroxyethyl) phenylpropyl benzoate, ←)
Hexenyl -4-(1-hydroxyethyl)benzoate is obtained.

Examples 12 to 18 The reaction, post-treatment, and
It was purified and the results shown in Table 2 were obtained.

(Margin below) Reference example> A production example of carboxylic acids (1) is shown below.

Reference Example 1 A 11-meter 4-tube flask was charged with o, aMa degree phosphate buffer (1) H7,0) 500-, and dl-4-
Methyl (1-acetoxyethyl)benzoate 22.2 f
, lipase (Amano P)4. OF, chloroform 4m/
and stir vigorously for 24 hours at 88±2°C under a nitrogen stream. After the reaction is complete, the reaction mixture is diluted with 800% ethyl acetate.
Extract twice. The obtained organic layer was concentrated, and the concentrated residue was purified by silica gel column chromatography (eluent: toluene-ethyl acetate) to obtain methyl 4-(1-hydroxyethyl)benzoate (8.5%).
IC yield 47%, Ctx) D = +46° (c = 1
, CHCAa)) and the asymmetric hydrolysis residue (-)-4
-(1-acetoxyethyl)methylbenzoate 10.5
IC yield 47%, (a'''J D = -96° (
c=1, CHCA'a)] was obtained. I got it here (−
Methyl 1-3-4-(1-hydroxyethyl)benzoate8. Dissolve Of in 80% of tetrahydrofuran and add 20%
Add 40 kg of sodium hydroxide and stir vigorously at room temperature for 5 hours. After the reaction was completed, the pH was adjusted to 8 with 4N hydrochloric acid, extracted with 400 rnl of ether, washed with saturated brine, and organic II was concentrated under reduced pressure to obtain a concentrated residue (→-4-(1
-Hydroxyethyl)benzoic acid 6.72 IC yield 91%
, ca], =+a9. o.

(c=1.methanol)] was obtained.

N~IR (60MHz, CDC/a) δ(pI)m
) 2.0 (OH1bs) 1.6 (CH
9CH,d) 5.9 (Chi B CH,q) 7.4~8.1 (Ar-H,dd)I Q,7 (
C0OH, b s ) Also, ←)-methyl-4-(1-acetoxyethyl)benzoate8. Of(g)-4-(1
Hydrolysis reaction and post-treatment were carried out in the same manner as for methyl -hydroxyethyl)benzoate, resulting in 5.61 g of ←)-4-(1- and droxyethyl)benzoic acid [yield 92%, [α], =
-85.66 (c=1, methanol)] Reference example 2 d/-4-(1-acetoxyethyl)methyl benzoate was replaced with d#-4-(acetoxyethyl)-4-biphenylcarboxylic acid. Ethyl (+)-4-(1-hydroxyethyl)-4-pyrophenylcarboxylate was obtained by carrying out the asymmetric hydrolysis reaction, post-treatment and purification treatment according to Reference Example 1 except for using ethyl acid 15.6F. 4N((:α)D=+8
6° (C=1, CH(J'a), melting point 75°C
] and ←)-4-(1-acetoxyethyl)-4-biphenylcarboxylic acid ethyl 7,41 (: (α)D=-8
7″ (c=1, CHC#a), melting point 46-47′
C') was obtained. Of these, ethyl (t)-4-(1-hydroxyethyl)-4-biphenylcarboxylate 6, Of
was added to a mixture of 20% potassium hydroxide aqueous solution (60tRt) and methanol (60%), and after stirring at room temperature for 6 hours,
After adding 150% of water and adjusting the pH to 3 with 8N hydrochloric acid, the resulting precipitate was collected with P and washed with water. ) was obtained as a white solid.[α].=+44°
(c=Q, 4, dimethylformamide) Melting point 222~
228°C (aec, ) NMR (60MHz, M dimethyl sulfoxide) 5.2
(-OH, b s ) 7.4-8.1 (Ar-H, m) 12.9 (-COOH, b s ) Also, it is an asymmetric hydrolysis residue←)-4-(1-acetoxyethyl) -4'-Biphenylcarboxylic acid ethyl 7, Of was similarly hydrolyzed and post-treated, f-) -
5.18g (yield 95%) of 4-(1-hydroxyethyl)-41-biphenylcarboxylic acid was obtained.

Claims (2)

[Claims] (1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R represents an alkyl group or alkenyl group with 2 or more carbon atoms, and m is 1. * indicates an asymmetric carbon atom Optically active carboxylic acid esters represented by (2) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, n is 1 or 2. The * mark indicates an asymmetric carbon atom.) In the presence of the substance, a compound of the general formula R'-X (wherein R' represents an aralkyl group, an alkenyl group, a lower alkyl group, a lower alkoxy group, or an aralkyl group optionally substituted with a halogen atom; X is a halogen atom) or −OSO_2R″′, where R
``'' indicates a lower alkyl group or an optionally substituted phenyl group) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R' , n and * are the same as above.) A method for producing optically active carboxylic acid esters.