JPS5910336B2 - Asymmetric synthesis method of primary chrysanthemum acid ester - Google Patents

Description

[Detailed description of the invention] The present invention relates to a method for asymmetric synthesis of primary chrysanthemum esters.

More specifically, it is a method for producing optically active monochrylate ester, which is characterized by reacting diazo formate and 2,5-dimethyl-2.4-hexadiene using an asymmetric copper complex as a catalyst. Daiichichrysanthemum acid is an important substance as an intermediate for synthetic pyrethroid insecticides, but it has two asymmetric carbon atoms in one molecule, so d-trans,
It exists in four stereoisomers: l-trans, d-cis, and 1-cis.

Among these, d-trans and d-cis are known to be particularly effective as raw materials for insecticides. Furthermore, chrysanthemum acid obtained from natural pyrethrum also has a d-trans structure. There are two possible methods for obtaining optically active chrysanthemum acid by synthetic methods.

One is to optically resolve the racemate once synthesized, and the other is to perform direct asymmetric synthesis. One of the methods for synthesizing primary chrysanthemum acid is to react diazodiacetate with 2,5-dimethyl-2,4-hexadiene in the presence of a copper catalyst, and hydrolyze the resulting chrysanthemum acid ester. There is something.

The present inventors have been conducting research on the asymmetric synthesis method of primary chrysanthemum acid ester for some time. We have discovered a method for producing an optically active primary chrysanthemum acid ester, which is characterized by reacting it with 2.4-hexadiene (see Japanese Patent Application No. 28457/1983).

The present inventors further investigated the copper complex used as an asymmetric catalyst in this reaction, and found that it has the general formula (I) (wherein, C* represents an asymmetric carbon atom).

R1 and R2 each represent an alkyl group, an aralkyl group, or an aryl group. X and Y each represent a hydrogen atom. We have found that the copper complex derived from the optically active Schiff base shown in ) is particularly effective as an asymmetric catalyst.

As the copper complex of the optically active Schiff base of general formula (I),
- Examples include mononuclear complexes of the general formula (), (), and dinuclear complexes of the general formula () (Japanese Patent Application Laid-Open No. 50-1843
9 and 50-151842). (
In the formula, C*, R1, R2, X and Y all have the same meanings as above.

L represents a neutral monodentate ligand. ) The present inventors further investigated the diazoacetate used as a substrate in this asymmetric synthesis reaction, and found that the general formula () (in the formula,
R represents a cycloalkyl group, an aralkyl group, or a secondary or tertiary alkyl group.

It has been found that the diazoacetic acid ester shown in ) is particularly effective for obtaining the produced primary chrysanthemum acid ester with good optical purity.

This fact was completely unexpected from the reaction results using primary alkyl esters such as ethyl diazoacetate. The present invention was completed based on this new knowledge. That is, the diazoacetate represented by the general formula (V) and 2,5-dimethyl are prepared using the asymmetric copper complex represented by the general formula () derived from the optically active Schiff base represented by the general formula (1) as a catalyst. This is a method for producing optically active primary chrysanthemum acid ester, which is characterized by reacting with -2,4-hexadiene. The substituent R of the diazoacetate represented by the general formula (V) is as described above, but the following can be more specifically exemplified.

(a) As the cycloalkyl group, cyclopentyl, 2
-methylcyclopentyl, cyclohexyl, 2-methylcyclohexyl, 2,2-, 2,5- or 2,6-dimethylcyclohexyl, 2,2,6-trimethylcyclohexyl, cyclooctyl, cyclododecyl and the like. Alcohol residues of natural or non-natural polycyclic alcohols are also effective. Examples include tanthyl, isotantyl, neotantyl, neoisotantyl, carbutanthyl, bornyl, isobornyl, 2-norbornyl, 1- and 2-adamantyl, and the like. (b
) Aralkyl groups include benzyl, benzhydryl, trityl, 1- or 2-indanyl, and the like.

(c) Secondary or tertiary alkyl groups include isopropyl, Sec-butyl, t-butyl, 1-methylheptyl and the like.

The diaA swindle esters of general formula () include esters with an achiral structure as well as those with a chiral structure.

In the latter case, either enantiomer or its racemate can be used in this reaction. Furthermore, if the primary chrysanthemum acid ester produced by this reaction has a certain level of insecticidal power, it can be used as is as an insecticide. There are no particular limitations on the method for synthesizing the diazoacetic acid ester of general formula (V), but the following may be listed, for example.

:;) A method of oxidizing the ester of glycine with nitrous acid or nitrite ester.

For example, 0rg. Synthesesc011. V01
4, p. 424 and N. Takamura,. T. Mi
zuguchi,. K. KOgasS. Yamada,
．． TetrahedrOnl3l, 227 (1975)
reference. The ester of glycine can be synthesized by reaction of glycine with the corresponding alcohol or with the corresponding olefin. (9) What is called Regitz's method. That is, a method in which p-toluenesulfonyl azide is allowed to act on the acetoacetate to once obtain 2-diazoacetoacetate, and then this is decomposed with an alkali. For example, 0rg. Syntheses.
C011. See page 79 of V01.5J. (111) H.O.
This is called the use method.

That is, a method in which an alcohol corresponding to the acid chloride of p-toluenesulfonylhydrazone glyoxylate is reacted in the presence of a base. For example, 0rg. Syntheses.
C011. See V01.5, page 258. The optically active Schiff base of the general formula (1) is synthesized by the reaction of the optically active amino alcohol of the general formula () (for example, JP-A-50-29535) and the salicylaldehyde derivative of the general formula (JP-A-50-29535). Publication No. 50-24254).

(In the formula, C8, R1, R2, X and Y are as described above.

) Substituents R1 and R2 in general formula () include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, 2
-butyl, t-butyl, octyl, cyclohexyl, cyclohexylmethyl, benzyl, bendhydryl, 2.
These include 2-diphenylethyl, phenyl, tolyl, naphthyl, and the like.

As R2, a phenyl group having at least one substituent at the o-1 position is excellent.

The 2-monosubstituted phenyl group includes 2-methoxyphenyl, 2
-ethoxyphenyl, 2-propoxyphenyl, 2-isopropoxyphenyl, 2-butoxyphenyl, 2-t
-butoxyphenyl, 2-octyloxyphenyl, 2
-benzyloxyphenyl, 2-phenoxyphenyl, etc.

As the 2,5-disubstituted phenyl group, 2-methoxy-5
-methylphenyl, 2-butoxy-5-methylphenyl,
5-methyl-2-octyloxyphenyl, 2-benzyloxy-5-methylphenyl, 5-t-butyl-2-
Methoxyphenyl, 2-butoxy-5-t-butylphenyl, 5-t-butyl-2-octyloxyphenyl,
2-benzyloxy-5-t-butylphenyl, 4-methoxybiphenyl-3-yl, 4-butoxybiphenyl-3-yl, 4-octyloxybiphenyl-3-yl, 4-benzyloxybiphenyl-3-yl -il, 2.5-
Dimethoxyphenyl, 2,5-dibutoxyphenyl, 2
-5-dibutoxyphenyl, 2,5-dioctyloxyphenyl, 2,5-dibenzyloxyphenyl, etc.

Substituents X, .
Y is as described above. Examples of the substituent containing a zero atom include 0H. 0R' (1? represents an alkyl, aralkyl, or aryl group. The same applies hereinafter), 0C
0R', CHO, . COR', COOHlCOOR',
CONH2, CN. NH2, NIIR(N(R,,N
HCOR', NO2, halogen atom, SH. SR',S
OR', SO2R', SO, H. Examples include SO3R'. Examples of the salicylaldehyde derivative of general formula () include the following compounds.

Namely, salicylaldehyde, o-vanillin, 3-ethoxysalicylaldehyde, 3,5-dibromsalicylaldehyde, 5-chlorsalicylaldehyde, 3-nitrosalicylaldehyde, 3-isopropyl-6-methylsalicylaldehyde, 2-hydroxy-1 -naphthaldehyde, 1-hydroxy-2-naphthaldehyde, etc.

More specific examples of the optically active Schiff base of general formula (1) include the following, and either the (8) or (S) form thereof may be used. That is, N
-Salicylidene-2-amino-1,1-di(2-methoxyphenyl)-3-phenyl-1-propanol, N-
Salicylidene-2-amino-1.l-di(2-isopropoxyphenyl)-3-phenyl-1-propanol,
N-Salicylidene-2-amino-1,1-di(5-t-
Butyl-2-isopropoxyphenyl)-3-phenyl-1-propanol, N-salicylidene-2-amino-
1,1-di(2-butoxy-5-t-butylphenyl)
-3-phenyl-1-propanol, N-salicylidene-2-amino-1,1-di(5-t-butyl-2-isopropoxyphenyl)-1-propanol, N-salicylidene-2-amino-1・1-di(2-butoxy-5-
t-butylphenyl)-1-propanol, N-salicylidene-2-amino-1,1-di(5-t-butyl-2
-octyloxyphenyl)-1-propanol, N-
(3-methoxysalicylidene)-2-amino-1.1-
Di(5-butyl-2-octyloxyphenyl)-1-
Such as propanol. The complex of general formula () is = general formula (
It is synthesized by the reaction of 1) Schiff's base with a cupric salt (for example, cupric acetate) (Japanese Unexamined Patent Publication No. 50-24254). In carrying out the method of the present invention, there is no restriction on whether the asymmetric copper complex of general formula () used as a catalyst is soluble or insoluble in the reaction system.

Further, the catalyst recovered and purified by an appropriate method can be used again. Asymmetric copper catalyst of general formula () and general formula (
The molar ratio of V) to the diazoacetic ester is not particularly limited, but usually takes a value from 0.001 to 0.1.

Although the method of the present invention can be carried out without a solvent in 2,5-dimethyl-2,4-hexadiene, it can also be carried out using a suitable solvent. There is no particular restriction on the reaction temperature when carrying out the method of the present invention, but it is usually -5
A temperature between 0°C and 150°C is suitable. Especially the reaction 2
- When carrying out the reaction below the melting point of 5-dimethyl-2-4-hexadiene (15°C), it is desirable to add an appropriate solvent to the reaction system. Suitable solvents include aromatic hydrocarbons such as benzene, toluene and xylene. The present invention will be explained in more detail with reference to Examples below, but the present invention is of course not limited to these.

Generally, in an asymmetric synthesis reaction, there is a difference between the absolute configuration of the substance that induces asymmetry and that of the substance that induces asymmetry.
A unique correlation exists.

Therefore, in the examples of the present invention, when the enantiomer of the asymmetric copper complex is used as a catalyst and the enantiomer of the diazoacetate is used as a substrate, the produced primary chrysanthemum ester and It is obvious that the corresponding enantiomers of chrysanthemum acid can also be obtained. In addition, in the following Examples and Reference Examples, the trans fraction (%) and the optical purity of the cis isomer and the trans isomer are values calculated as follows.

Example 1 (S)-N-salicylidene-2-amino-1
・Dinuclear copper complex derived from 1-di(5-t-butyl-2-isopropoxyphenyl)-1-propanol (in general formula (), R1 = methyl, R2 = 5-
Corresponds to t-butyl-2-isopropoxyphenyl.

)0.37V (0.3 mmol) was dissolved in 9.9y (90 mmol) of 2,5-dimethyl-2,4-hexadiene, and the above diene 6.6y (60 mmol) and l-tantyl diazoacetate were added thereto. 6.7f7(3
0 mmol) was added dropwise over 6 hours while stirring. The system was heated to 75℃ until the generation of nitrogen gas was observed, but as soon as the reaction started, the temperature inside the system decreased to about 1℃.
The temperature was lowered to 40°C over time, and the dropwise addition was continued at the same temperature thereafter. At the end of the reaction, almost quantitative nitrogen gas (744ml
)There has occurred. After distilling off the excess diene from the reaction mixture (boiling point 50°C/201mHg), l-tantyl monochrylate 6.34V (yield 69.0%) was distilled to boiling point 123°C/201mHg.
Obtained as an oil at 0.2 nHg. αD-52.6゜(
undiluted, 1 dm). The optical isomer ratio of primary chrysanthemum acid contained in this sample was determined using a glass capillary column (liquid phase QF-
1) (inner diameter 0.26n, length 25m) was analyzed by gas chromatography and the results were as follows. d-trans form, 4.3%; l-trans form, 65.
7%; d-cis form, 5.1%; l-cis form, 25.0%
.

Example 2 Exactly the same reaction as in Example 1 was carried out using dl-tantyl diazoacetate instead of l-tantyl diazoacetate.

When the reaction mixture was treated in the same manner, tantyl monochrylate 5.631 (yield 67.3%) had a boiling point of 120°C.
/0.151 mHg as an oily product. α
D - 51.7° (undiluted, 1 dm). The cis/trans ratio for primary chrysanthemum acid was 30/70 (as analyzed by gas chromatography). Chrysanthemum acid obtained by alkaline hydrolysis of this sample (yield 60%) was
1-Methylheptyl ester was derived and analyzed by gas chromatography. As a result, the optical isomer ratio for daichusic acid was as follows.

d-trans form, 6.1%; l-trans form, 76.2
%; d-cis form, 4.5%; l-cis form, 13.2%.

Reference Example 1 Exactly the same reaction as in Example 1 was carried out using ethyl diazoacetate (30 mmol of 3.4 t) in place of l-tantyl diazodiacetate.

When the reaction mixture was treated in the same manner, ethyl monochrylate (4.0r, yield 68%) had a boiling point of 60°C/0.5
Obtained as an oily product of 11 Hg. αD-11.8
Form 3 (undiluted, 1 dm). The cis/trans ratio for primary chrysanthemum acid was 45/55 (as analyzed by gas chromatography). Chrysanthemum acid obtained by alkaline hydrolysis of this sample (yield 90%), boiling point 80°C/0.51
mHg, [α]D-35,0, (C.2.1, chloroform) was introduced into 1-1-methylheptyl ester and subjected to analysis by gas chromatography.

The optical isomer ratio for Daiichichrysanthemum acid was as follows.
d-trans form, 9.0%; l-trans form, 45.8
%; d-cis form, 8.4%; 1-cis form, 36.8%.
Example 3 8-N-Salicylidene-2-amino-1,1-di(5-
Dinuclear copper complex of t-butyl-2-octyloxyphenyl)-1-propanol (in general formula (), R1 =
Methyl, corresponds to R2=5-t-butyl-2-octyloxyphenyl.

) 0.3f (0.2 mmol) to 2,5-dimethyl-2
・4-Hexadiene 17.6? (160 mmol), and the above diene 4.4 V (40 mmol) and 4.5 V (20 mmol) of 1-tantyl diaA sulfate were added dropwise thereto over 7 hours with stirring. Heat (75°C) until the diazo compound begins to decompose and nitrogen gas begins to be generated.
), but thereafter the dropwise addition was continued at 40°C. At the end of the dropping, a substantially quantitative amount of nitrogen gas (480 m0) was generated.
Excess diene from the reaction mixture (boiling point 45°C/2011H)
g> was distilled off, the residue was distilled under reduced pressure to obtain Daiichi chrysanthemum acid 1
- Tanthyl 4.7P (yield 76%, boiling point 123°C/0.
211Hg) was obtained. The l-tantyl ester was analyzed by gas chromatography using a glass capillary column (liquid phase QF-1) to determine the optical isomer composition of the primary chrysanthemum acid in the ester. d-trans form, 89.
9%; l-trans form, 2.7%; d-cis form and l
- Cis form (cannot be separated) total 7.4% Fraction of trans form in ester is 93%, optical purity of trans form is 94
It is calculated as %.

1-tanthyl ester 4.2V1 Caustic potassium 1.8f1 Water 1.5ml and ethanol 11ml mixture in 100ml
The mixture was heated and stirred at ℃ for 7.5 hours.

After ethanol was distilled off from the reaction mixture, the residue was diluted with water and extracted with ether. The alkaline aqueous layer was made acidic with dilute sulfuric acid and extracted with toluene. After washing the organic layer with water and drying,
Toluene was distilled off under reduced pressure to obtain 2.4t of daisies chrysanthemum acid (yield 90%).
) was obtained. Daisi chrysanthemum acid was reacted with (d)-2-octanol, and the resulting diastereomer was analyzed by gas chromatography to determine the optical isomer composition of chrysanthemum acid.

d-trans form, 90.4%; l-trans form, 4.7
%; d-cis form, 3.6%; l-cis form, 1.3% Optical purity is 90% for trans form and 47% for cis form.
It is calculated as %.

Regarding the analytical method of optical isomers of Daiichichrysanthemum acid, please refer to A. Mur
anO. Agr. BlOl. Chem. , 36, 220
3 (1972).

Examples 4 to 7 Experiments similar to those in Example 3 were conducted using the dinuclear asymmetric copper complex shown in Table 1 and 1 tantyl diazoacetate.

The results are summarized in Table 1. The trans fraction of 1-tantyl chloride was determined by gas chromatographic analysis of the 1-tantyl ester. In addition, the optical purity of the primary chrysanthemum acid obtained by hydrolysis was determined by gas chromatographic analysis of -1-methylheptyl ester. When a (S) monoconfigured catalyst is used, levorotatory monochroic acid is produced.Reference Example 2 Diazoacetic acid 1-
1-Methyl chrysanthemum acid was synthesized from tantyl and 2,5-dimethyl-2,4-hexadiene.

The results are shown in Table 1. Examples 8 to 19 Diazoacetic esters and asymmetric copper complexes shown in Table 2 (corresponding to the cross-configuration, R,-methyl, and R2=5-t-butyl-2-octyloxyphenyl in the general formula ()).

), an experiment similar to that in Example 3 was conducted. The results are summarized in Table 2.

The trans fraction in the primary chrysanthemum acid ester produced was determined by gas chromatographic analysis of the ester.

The optical purity of the primary chrysanthemum acid obtained by hydrolysis of the ester was determined by gas chromatographic analysis of (3)-1-methyl-1-hebutyl ester.

Note that dia-A acetate was synthesized by the following method (A) or method (B).

Method (A): A corresponding glycine ester is diazotized with isoamyl nitrite.

The reaction formula is as follows. ROM-+H2NCH
2COOR-+N2CHCOOR As a typical example, Reference Example 4 shows a method for synthesizing 1-tantyl diazoacetate.

Method (B): The alcohol is converted into acetoacetate by the action of diketene, then α-diazoacetoacetate by the action of toluenesulfonyl azide, and then diazoacetate by the action of sodium methoxide.

The reaction formula is as follows. As a typical example, Reference Example 5 shows a method for synthesizing 2,3,4-trimethyl-3-pentyl diazoacetate.

Reference Example 3 Ethyl monochrylate was synthesized from ethyl diazoacetate and 2,5-dimethyl-2,4-hexadiene using the same asymmetric copper complex as in Examples 8 to 19 as a catalyst.

The results are shown in Table 2. Reference example 4 Glycine l-tantyl ester 19.7r (0.092
A mixture of 12.0f7 (0.10 mol) of isoamyl nitrite, 1.6 t (0.027 mol) of acetic acid and 400 ml of chloroform was heated under reflux for 25 minutes with stirring.

The reaction mixture was washed with IN sulfuric acid, saturated aqueous sodium bicarbonate, and then water.

After drying and concentrating the organic layer, the obtained residue 21t was purified by silica gel column chromatography 160f (methylene chloride) to obtain 15.0f (73%) of 1-tantyl diazoacetate.

Yellow crystal (α) D-86.8 δ1.0) IR (film) 2125c! n-1 NMR (chloroform, TMS), 5.29 ppm K. for glycine 1-tantyl ester. Harada
、． THayalcawalBull. Chem. S.O.
c. Japan,. 3! , 191 (1964).

Reference example 52,3,4-trimethyl-3-pentanol 24.3V (0.18 mol) and triethylamine 0
．． Diketene 15.7f7 (0.186
mol) was added dropwise at 70°C.

The reaction mixture was further stirred at 110°C for 1.5 hours and then distilled under reduced pressure to obtain the corresponding acetoacetate (boiling point 8
4°C/0.6g1Hg), 35.3f (yield 88%) was obtained.

To a mixture of the above ester 35.3r (0.164 mol), triethylamine 17f7 (0.168 mol) and 200 ml of acetonitrile, p-toluenesulfonyl azide 38f (0.164 mol) was added dropwise at room temperature.

The reaction mixture was further stirred for 1.5 hours and then concentrated under reduced pressure.

The residue was extracted with 200 ml of ether, and the organic layer was washed twice with an aqueous solution of 12.6 y of caustic potassium. After drying and concentration, the corresponding α-diazoacetyl acetate 40y was obtained.
A sodium methoxide solution prepared from 4.27 ml of sodium and 65 ml of methanol was added to a mixture of 407 of the above ester and 65 ml of methanol at 0°C.

The reaction mixture was stirred for a further 1 hour at 0°C, then poured into ice water at 30°C.
The organic layer was washed with water, dried, concentrated, and then distilled to obtain 2,3,4-trimethyl-3-pentyl diazoacetate (boiling point 59℃/ 0.2 uHg) 20.9? (yield 64%) was obtained.

Claims (1)

[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, C^* represents an asymmetric carbon atom. R_1 and R_2 are an alkyl group, an aralkyl group,
Represents any aryl group. X and Y each represent a hydrogen atom. ) is the general formula derived from the optically active Schiff base represented by ▲ There are numerical formulas, chemical formulas, tables, etc. ▼ [In the formula, *, X, Y, R_1 and R_2 are as described above. diazoacetic acid represented by the general formula N_2CHCOOR (wherein R represents either a cycloalkyl group, an aralkyl group, or a secondary or tertiary alkyl group) using an asymmetric copper complex represented by the following as a catalyst. Ester and 2,5-dimethyl-
1. A method for producing optically active primary chrysanthemum acid ester, which comprises reacting with 2,4-hexadiene.