JPH0421654B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Industrial Application Field The present invention relates to a novel method for producing α-alkyl-3(E)-alkenoic acid esters useful as synthetic intermediates for fragrances and organic compounds.

More specifically, the present invention is based on the following formula (2) However, in the formula, R, R1 and R2 represent lower alkyl groups. After the isomerization reaction, the following formula (1) is obtained. However, in the formula, R, R1 and R2 represent lower alkyl groups.

(b) Conventional technology Conventionally, 2 having an alkyl substituent at the α-position
A method for synthesizing 3(E)-alkenoic acid esters by directly isomerizing the double bond of (E)-alkenoic acid esters is not yet known.

Conventional proposals for synthesizing 3(E)-alkenoic acid esters having an alkyl substituent at the α-position include:
For example, Agr・Biol・Chem・, 36, (5) 793-797
(1972) and shown in the process diagram below is known.

In the formula, R, R1 and R2 represent lower alkyl. According to the method in the above process diagram, the above formula (A)3(E)-
An alkyl alkenoate is reacted with an alkyl bromide in the presence of an alkaline amide in liquid ammonium to alkylate it to the α-position, resulting in the formula (B) α-alkyl-3(E)-
Alkyl alkenoates (e.g. 2-butyl-3-
A method for synthesizing methyl buntenoate (66% yield) is disclosed.

In addition, as conventional proposals for isomerizing double bonds, for example, Helv Chim Acta, 64, (94) 1023~
1025 (1981) and shown in the process diagram below is known.

In the formula, R and R2 represent an alkyl group.

According to this proposal, a linear ethyl alkenoate of the above formula (a)2(E) without an alkyl substituent at the α-position is mixed with lithium diisopropylamide (LDA) and hexamethyl phosphorotriamide in an ammonium chloride solution. The double bond is isomerized in the presence of amide (HMPT) to produce ethyl 3(E)-alkenoate of the above formula (b) having a double bond at the 3-position and 3 of the formula (c).
A method for obtaining a mixture of (Z)-ethyl alkenoates is disclosed. According to this method, most of the double bonds change from the trans-form to the cis-form,
It is disclosed that about 90% of the cis-formula (c) is produced.

(c) Problems to be solved by the invention A 3(E)-alkyl alkenoate having a double bond at the 3-position is alkylated at the α-position to form an α-
In the above conventional proposal for synthesizing alkyl-3(E)-alkenoates, the yield is 66% (in the case of methyl α-butyl-3(E)-bentenoate), which is not necessarily a satisfactory method. Furthermore, during the alkylation reaction, movement of double bonds tends to occur, making it difficult to obtain the desired product with high purity. Furthermore, since liquid ammonium is used during the reaction, this method cannot be said to be industrially advantageous in terms of equipment and operation.

Furthermore, using lithium diisopropylamide and hexamethyl phosphorotriamide as isomerization reagents similar to those used in the method of the present invention, a double bond of linear ethyl 2(E)-alkenoate without an alkyl substituent at the α-position was formed. In previous proposals for isomerization, ethyl 3(Z)-alkenoates are obtained as the main product, and ethyl 3(E)-
Almost no ethyl alkenoate is obtained.

(c) Means for Solving the Problems The present inventors have conducted intensive research on a method that can avoid problems such as the isomerization of double bonds as proposed above and that can be produced industrially.

As a result, when the previously proposed isomerization reagents for lithium diisopropylamide (LDA) and hexamethylphosphorotriamide (HMPT) have an alkyl substituent at the α-position, 2(E)-3-alkenoic acid esters In the isomerization of isomerization, it was unexpectedly discovered that the 3(Z)-isomer was not produced at all and it was an effective reagent for selectively obtaining only the 3(E)-isomer. In other words, the following formula (2) However, in the formula, R, R1 and R2 represent lower alkyl. Formula (1) However, in the formula, R, R ₁ and R 2 have the same meanings as above, and it has been discovered that an alkyl α-alkyl-3(E)-alkenoate represented by the following can be easily produced industrially with high purity and high yield.

Therefore, an object of the present invention is to provide a method for easily producing the compound of formula (1) with high purity at a lower cost and industrially advantageous than the conventional methods described above.

The above embodiments, including production examples of the compound of formula (2) of the present invention, can be expressed as follows in a process diagram.

The compound of formula (2) used as a raw material in the present invention can be easily obtained on the market, but it can also be obtained, for example, by the method shown in the process diagram (latest organic synthesis reaction: 2
It can also be easily manufactured by using a version (written by House, published by Hirokawa Shoten).

In the above formula (2), preferred examples of the lower alkyl group for R include alkyl groups in the range of about C1 to C11. Further, as an example of the lower alkyl group for R2, a range of about C1 to C4 can be preferably exemplified. Also, R2
Examples of lower alkyl groups include, for example, C1 to C4
Preferred examples include ranges of degree.

Examples of compounds included in the compound of formula (2) above include methyl α-methyl-2(E)-bentenoate, α-methyl-2(E)-butyl bentenoate,
-Methyl-2(E)-methyl hexenoate, α-methyl-2(E)-propyl hexenoate, α-methyl-
2(E)-ethyl heptenoate, α-methyl-2(E)
-butyl heptenoate, α-methyl-2(E)-meyuthyl octenoate, α-methyl-2(E)-propyl octenoate, α-methyl-2(E)-ethyl nonenoate, α-methyl-2( E)-butyl nonenoate, α-
Methyl-2(E)-methyl decenoate, α-methyl-
2(E)-propyl decenoate, α-methyl-2(E)
-Ethyl undensenate, α-methyl-2(E)-
Butyl undecenoate, α-methyl-2(E)-methyl dodecenoate, α-methyl-2(E)-propyl dodecenoate, α-methyl-2(E)-ethyl tridecenoate, α-methyl-2(E) )-butyl tridecenoate, α-methyl-2(E)-methyl tetradecenoate, α-methyl-2(E)-propyl tetradecenoate, α-methyl-2(E)-ethyl pentadecenoate, α-methyl-2 (E)-Butyl pentadecenoate, α-ethyl-2(E)-methylbentenoate, α
-ethyl-2(E)-propylbentenate, α-ethyl-2(E)-ethylhexenoate, α-ethyl-
2(E)-butyl hexenoate, α-ethyl-2(E)
-Methyl heptenoate, α-ethyl-2(E)-propyl heptenoate, α-ethyl-2(E)-ethyl octenoate, α-ethyl-2(E)-butyl octenoate, α-ethyl-2(E)-butyl E)-Methyl nonenoate, α-
Ethyl-2(E)-propyl nonenoate, α-ethyl-2(E)-ethyl decenoate, α-ethyl-2(E)
-butyl-decenoate, α-ethyl-2(E)-methyl undecenoate, α-ethyl-2(E)-propyl undecenoate, α-ethyl-2(E)-methyl dodecenoate, α-ethyl-2( E)-ethyl tridecenoate, methyl α-ethyl-2(E)-tetradecenoate, methyl α-ethyl-2(E)-pentadecenoate, methyl α-propyl-2(E)-pentenoate,
α-propyl-2(E)-propylhexenoate, α
-ethyl propyl-2(E)-heptenoate, methyl α-propyl-2(E)-octenoate, ethyl α-propyl-2(E)-nonenoate, α-propyl-2
(E)-Ethyl decenoate, α-propyl-2(E)-
Methyl undecenoate, α-propyl-2(E)-methyl dodecenoate, α-propyl-2(E)-ethyl tridecenoate, α-propyl-2(E)-methyl tetradecenoate, α-propyl-2(E)-methyl )-methyl bentadecenate, α-butyl-2(E)-methylbentenoate, α-butyl-2(E)-butyl hexenoate, α-butyl-(E)-methylheptenoate, α-
Butyl-2(E)-propyl octenoate, α-butyl-2(E)-methyl nonenoate, α-butyl-2
(E)-propyl decenoate, α-butyl-2(E)-
Ethyl undecenoate, α-butyl-2(E)-ethyl dodecenoate, methyl α-butyl-2(E)-tridecenate, α-butyl-2(E)-propyl tetradecenoate, α-butyl-2(E) )-methyl pentadecenoate and the like.

From the compound of formula (2) as described above, the compound of formula (1) of the present invention
The compound can be synthesized by, for example, reacting the compound of formula (2) while dropping an organic solvent solution of hexamethylphosphorotriamide (HMPA) and lithium diisopropylamide.

The reaction temperature can be selected appropriately, but
For example, a range of about -78° to about 70°C, more preferably a range of about -78° to about 0°C can be mentioned. Further, the reaction time can be appropriately selected depending on the above reaction temperature, but for example, about 0.2
~A range of about 10 hours, more preferably about 0.5~
A range of about 5 hours can be exemplified.

The amount of hexamethylphosphorotriamide used in the above reaction is, for example, about 1 to about 3 mol, preferably about 1.1 to about 1.5 mol, based on the compound of formula (2) above. be able to. The amount of lithium diisopropylamide to be used is, for example, about 1 to about 3 mol, preferably about 1.1 to about 3 mol, based on the compound of formula (2) above.
A range of about 1.5 mol can be exemplified. or,
Examples of organic solvents used in the above reaction include tetrahydrofuran, ether, benzene,
Examples include toluene and 1,2-dimethoxyethane. The amount of these organic solvents used includes
Although there are no particular limitations and the amount can be selected as appropriate, a preferred example is a range of about 1 to about 20 times the weight of the compound of formula (2) above.

After the reaction is completed, the crude compound of formula (1) can be easily obtained by treating the reaction product with a saturated aqueous ammonium chloride solution and extracting with a suitable extraction solvent according to a conventional method. The compound of formula (1) is
For example, a highly pure compound of formula (1) can be obtained by purification by means such as distillation or column chromatography.

Thus, specific examples of compounds of formula (1) that can be synthesized as described above include, for example, methyl α-methyl-3(E)-heptenoate, α-methyl-3
(E)-Butyl heptenoate, α-methyl-3(E)-
Methyl hexenoate, α-methyl-3(E)-propyl hexenoate, α-methyl-3(E)-ethyl heptenoate, α-methyl-3(E)-butyl heptenoate, α-methyl-3(E)-butyl )-methyl octenoate, α
-Methyl-3(E)-propyl octenoate, α-methyl-3(E)-ethyl nonenoate, α-methyl-3
(E)-Butyl nonenoate, α-methyl-3(E)-methyl decenoate, α-methyl-3(E)-propyl decenoate, α-methyl-3(E)-ethyl undecenoate, α-methyl -3(E)-butyl undecenoate,
α-Methyl-3(E)-methyl dodecenoate, α-methyl-3(E)-propyl dodecenoate, α-methyl-3(E)-ethyl tridecenoate, α-methyl-3
(E)-butyl tridecenoate, α-methyl-3(E)
-Methyl tetradecenoate, α-methyl-3(E)-
Propyl tetradecenoate, α-methyl-3(E)-
Ethyl pentadecenoate, α-methyl-3(E)-butyl petadecenate, α-methyl-3(E)-methylpentenoate, α-methyl-3(E)-propyl bentenoate, α-ethyl-3(E) )-ethyl hexenoate, α-ethyl-3(E)-butyl hexenoate, α
-ethyl-3(E)-methyl heptenoate, α-ethyl-3(E)-propyl heptenoate, α-ethyl-
3(E)-ethyl octenoate, α-ethyl-3(E)
-Butyl octenoate, α-ethyl-3(E)-methyl nonenoate, α-ethyl-propyl nonenoate, α
-Ethyl-3(E)-ethyl decenoate, α-ethyl-3(E)-butyl decenoate, α-ethyl-3(E)
-methyl undecenoate, α-ethyl-3(E)-propyl undecenoate, α-ethyl-3(E)-methyl dodecenoate, α-ethyl-3(E)-ethyl todecenoate, α-ethyl-3( E)-methyl tetradecenoate, α-ethyl-3(E)-methyl pentadecenoate, α-propyl-3(E)-methyl pentenoate,
α-propyl-3(E)-propylhexenoate, α
-Ethyl propyl-3(E)-heptenoate, methyl α-propyl-3(E)-octenoate, ethyl α-propyl-3(E)-nonenoate, α-propyl-3
(E)-Ethyl decenoate, α-propyl-3(E)-
Methyl undecenoate, α-propyl-3(E)-methyl dodecenoate, α-propyl-3(E)-ethyl tridecenoate, α-propyl-3(E)-methyl tetradecenoate, α-propyl-3(E) )-methyl pentadecenoate, α-butyl-3(E)-methyl pentenoate, α-butyl-3(E)-butyl hexenoate, α-butyl-3(E)-methyl heptenoate, α
-Butyl-3(E)-propyl octenoate, α-butyl-3(E)-methyl nonenoate, α-butyl-3
(E)-propyl decenoate, α-butyl-3(E)-
Ethyl undecenoate, α-butyl-3(E)-ethyl dodecenoate, methyl α-butyl-3(E)-tridecenate, α-butyl-3(E)-propyl tetradecenoate, α-butyl-3(E) )-methyl pentadecenoate and the like.

The embodiments of the present invention will be described in more detail below with reference to Examples.

(d) Example (1) Synthesis of methyl α-methyl-3(E)-decenoate.

A flask was charged with 60 ml of dry tetrahydrofuran, and while cooling in a dry ice-acetone bath, n-butyllithium-hexane solution (0.126 mol) was added. Next, 12.8g of diisopropylamine (0.127
30 ml of dry tetrahydrofuran solution of -
Add in about 10 minutes while maintaining the dropwise reaction temperature between 50° and -55°C. After dropping, remove the cooling bath and stir at 0°C for 30 minutes. After cooling again at -50° to -55°C, a solution of 26.7 g (0.15 mol) of hexamethylphosphorotriamide in 30 ml of dry tetrahydrofuran is added over about 10 minutes.
Continue stirring at the same temperature for an additional 30 minutes. At this time, the reaction solution becomes a white suspension state. α− at the same temperature
A solution of 19.8 g (0.1 mol) of methyl 2(E)-decenoate in 30 ml of tetrahydrofuran is added.
After stirring at the same temperature for 2 hours, the reaction solution was poured into saturated aqueous ammonium chloride to complete the reaction. Separate the organic layer, extract the aqueous layer with ether, and combine the organic layers. Washing with water, washing with a dilute hydrochloric acid solution, washing with water, and washing with an aqueous sodium bicarbonate solution (200 ml each), followed by drying over anhydrous magnesium sulfate, ether was distilled off, and the residue was distilled under reduced pressure to obtain 14.1 g of the title compound (yield 71.4). %) was obtained. Boiling point 75-76℃/2mmHg. Gas chromatography analysis of this product revealed that the transformer ratio was 100%.

(2) Synthesis of methyl α-methyl-3(E)-pentenoate.

Example 1 was carried out in the same manner as in Example 1, except that 12.8 g (0.1 mol) of methyl α-methyl-2(E)-pentenoate was used instead of methyl α-methyl-2(E)-decenoate. The title compound can be obtained by
16.3g (83% yield) was obtained. Transformer ratio: 100%.

(3) Synthesis of ethyl α-propyl-3(E)-pentenoate.

Ethyl α-propyl-3(E)-pentenoate 14.0
The title compound was obtained in the same manner as in Example 1 except that 11.0 g (yield: 79 mol) of the title compound was used.
%)Obtained. Transformer ratio: 100%.

(4) Synthesis of methyl α-ethyl-3(E)-hexenoate.

Methyl α-ethyl-2(E)-hexenoate 15.6g
12.4 g (yield: 80%) of the title compound was obtained by carrying out the same procedure as in Example 1, except that (0.1 mol) was used. Transformer ratio: 100%.

(5) Synthesis of α-butyl-3(E)-propylhexenoate.

α-Butyl-2(E)-propylhexenoate 21.2
15.3 g (yield 72%) of the title compound was obtained by carrying out the same procedure as in Example 1 except that 15.3 g (yield 72%) of the title compound was used. Transformer ratio: 100%.

(6) Synthesis of ethyl α-methyl-3(E)-heptenoate.

Ethyl α-methyl-3(E)-heptenoate 14.0
10.9 g (yield 78%) of the title compound was obtained by carrying out the same procedure as in Example 1 except that (0.1 mol) was used.
Transformer ratio: 100%.

(7) Synthesis of butyl α-ethyl-3(E)-heptenoate.

Butyl α-ethyl-2(E)-heptenoate 21.2g
15.1 g (yield: 71.0%) of the title compound was obtained by carrying out the same procedure as in Example 1 except that (0.1 mol) was used. Transformer ratio: 100%.

(8) Synthesis of methyl α-methyl-3(E)-octenoate.

Methyl α-methyl-2(E)-octenoate 14.0g
10.4 g (yield: 74%) of the title compound was obtained by carrying out the same procedure as in Example 1 except that (0.1 mol) was used. Transformer ratio: 100%.

(9) Synthesis of α-methyl-3(E)-propyl nonenoate.

α-Methyl-2(E)-propyl nonenoate 21.2g
15.3 g (yield: 72%) of the title compound was obtained by carrying out the same procedure as in Example 1 except that (0.1 mol) was used. Transformer ratio: 100%.

(10) Synthesis of methyl α-butyl-3(E)-decenoate.

Methyl α-methyl-2(E)-decenoate 24g
16.6 g (yield 69%) of the title compound was obtained by carrying out the same procedure as in Example 1 except that (0.1 mol) was used. Transformer ratio: 100%.

(11) Synthesis of butyl α-ethyl-3(E)-undecenoate.

Butyl α-ethyl-2(E)-undecenoate 26.6
18.3 g (yield 69%) of the title compound was obtained by following the same procedure as Example 1 except that g (0.1 mol) was used.
Obtained. Transformer ratio: 100%.

(12) Synthesis of methyl α-propyl-3(E)-dodecenate.

Methyl α-propyl-2(E)-dodecenate 25.4
18 g (yield: 74%) of the title compound was obtained by carrying out the same procedure as in Example 1 except that 18 g (0.1 mol) of the title compound was used. Transformer ratio: 100%.

(13) Synthesis of methyl α-methyl-3(E)-tridecenoate.

Methyl α-methyl-2(E)-tridecenate 24g
15.3 g (yield: 68%) of the title compound was obtained by carrying out the same procedure as in Example 1 except that (0.1 mol) was used. Transformer ratio: 100%.

(14) Synthesis of ethyl α-butyl-3(E)-tetradecenoate.

Ethyl α-methyl-2(E)-tetradecenoate
By following the same procedure as Example 1 except that 30.9 g (0.1 mol) was used, 20 g (yield: 65 mol) of the title compound was obtained.
%)Obtained. Transformer ratio: 100%.

(15) Synthesis of butyl α-methyl-3(E)-pentadecenoate.

Butyl α-methyl-2(E)-pentadecenate 31
19.8g (yield 64%) of the title compound was obtained by carrying out the same procedure as in Example 1 except that g (0.1 mol) was used.
Obtained. Transformer ratio: 100%.

(e) Effects According to the present invention, it is possible to provide a method for industrially producing α-alkyl-3(E)-alkenoic acid esters useful as synthetic intermediates for fragrances and organic compounds at low cost and easily. can.

That is, 2 having an alkyl substituent at the α-position
A method for producing 3(E)-alkenoic acid esters by isomerizing double bonds from (E)-alkenoic acid esters, in which isomerization is performed in the coexistence of lithium diisopropylamide (LDA) and hexamethylphosphorotriamide. By reacting, it is possible to provide a method that can selectively produce only the 3(E)-isomer without producing the 3(Z)-isomer.

Claims (1)

[Claims] 1. The following formula (2) However, in the formula, R, R1 and R2 represent lower alkyl. The following formula (1) is characterized by an isomerization reaction: However, in the formula, R, R1 and R2 represent lower alkyl.