DE2634663B2 - Process for the preparation of an optically active alkyl chrysanthemum monocarboxylic acid ester - Google Patents

Description

R '

R ²

CH-C-OH

R ²

OH

derives in the

R ¹ benzyl or methyl and

R ² 5-t-butyl-2-isopropoxyphenyl,
5-t-butyl-2-heptyloxyphenyi,
5-t-butyl-2-butoxyphenyl or
5-t-butyl-2-octyloxyphenyl mean

in the absence of a solvent at a temperature of -50 to 150 ° C, thereby characterized in that as diazoacetate a compound of the formula

N ₂ CH -COOR

used, in which R methyl, ncomethyl, 1-adamantyl or «A-dimethyl- / I- (menthoxy) ethyl denotes.

2. The method according to claim I, characterized in that the molar ratio of copper complex to diazoacetate in the range of 0.001: 0, l lies.

Conversion of an alkyl dia / oacetate with 2,5-dimethyl-2,4-hexadiene in the presence of a copper catalyst (cf. G B-PS 7 40 014) and subsequent hydrolysis of the formed alkyl chrysanthemate.

The present invention relates to the asymmetric synthesis of alkyl chrysanthemates. From the BE-PS 7 87 473 a process for the production of an optically active alkyl chrysylemate is known, in which a Alkyl diazoacetate is reacted with 2,5-dimethy | -2,4-hexadiene in the presence of a copper catalyst which is coordinated with a chiral ligand, according to the following reaction scheme:

COOR

N, CHCOOR

CuIL *

COOR

wherein L ^{1 represents} a chiral ligand.

From DE-OS 24 07 094 it is known that asymmetric synthesis of alkyl chrysanthemates in an advantageous manner with a copper complex catalyze, which is coordinated with a chiral Schiffschen Base of the following formula (I)

X ¹ / -.

R ²

CH C OH
R-

X- ^v 'OH

The invention relates to the subject matter characterized in more detail in the claims.

Chrysanthemum monocarboxylic acid is known to be a important material for the production of synthetic pyrichroids. which are effective as insecticides. There are four stereoisomers of chrysanthemum monocarboxylic acid. namely, two kinds of geometric isomers, i.e. H. cis and trans, each of which is optical d- and l-lsomcrc Has. The pyrethroids derived from the d-trans and d-cis chrysanthemum monocarboxylic acids are for theirs particularly high insecticidal activity known. The naturally occurring chrysanthemum monocarboxylic acid is known to have a d-trans structure.

For the industrial production of optically active chrysanthemum monocarboxylic acid There are two possible methods. According to one of these methods, first the laeemisehe mixture synthesized, whereupon this is subjected to an optical separation. The second of these methods is direct Synthesis of the desired asymmetric optical isomer.

A known synthetic method for the preparation of chrysanthemum monocarboxylic acid consists in the where mean:

C * is an asymmetric carbon atom,
R ^{1 is} an alkyl radical with 1 to 10 carbon atoms or an aralkyl radical which optionally bears one or more alkoxy substituents with a total of 7 to 20 carbon atoms,

R ² aryl groups which carry one or more alkoxy substituents with a total of 7 to 30 carbon atoms,

X ¹ and X ² on their own
Hydrogen atoms,

Alkyl radicals with 1 to 10 carbon atoms,
Phenyl residues,

Alkoxyresic with 1 to 10 carbon atoms,
Halogen atoms or
Nitro groups, or
together a benzo groupc.

Forms the Schiff's base of the specified l-'ormcl I. a metal complex with divalent copper ion, three types of chclate are possible (with respect to the Chemistry of the metal complexes of Schiff bases see, for example, R. H. Holm, G. W. E ν e r c 11,) r. and A. Cha k r a before t y, "Progress in Inorganic Chemistry" 7, 83-214 [1966], Intersciencc Publishers, New York).

One of these chelates has the following dine structure

of the formula II, in which the Schiff base aiii three ligand behaves:

(M)

H R ¹ X N H R- I. I. -R ¹ A. Cu - γ O I. -O

wherein R ¹ and R ^{2 have} the meaning given.

The other chelate corresponds to the following monomers Structural formulas III or IV, in which the Schiff base is twofold or threefold Ligand behaves

(III)

(IV)

where R ¹ and R ^{2 have} the meaning given and L is a neutral, small number of ligands (with regard to the copper complex of N-salicylid-2-amino-ethanol, cf., for example, RP H on ghton and D. Pointer. | .Chcm .Soc. [1965] .4214).

The alkyldia / octal, which serves as the substrate in this asymmetric synthesis, was also investigated. It was found that the alkyldia / .oacclat the general formula V

N.C'MC'OOR

with a dimeric structure according to the general formula (II).

The diazoacetates of the given general Formula V can have either an aehiral or a chiral structure. In the latter case, any form of Enantiomeric or racemic modification used to carry out the process according to the invention will. If an alkyl chrysarithemate produced according to the invention shows an insecticidal effect, then it can as such can be used as an insecticide.

Although with regard to the process for the synthesis of the alkyl diazoacelates of the general formula V, none If there are restrictions, the following procedures should be mentioned as examples:

(A) Procedure: «jr diazotization of the corresponding Esters of glycine with nitrous acid or a nitrous acid ester (see, for example, Organic Syntheses, Coll. Vol. 4, 424 and N.Takamura, T. Mizoguchi, K. Koga and S. Yamada, Tetrahedron 31, 227 [1975]). The ester of glycine can be synthesized by reacting glycine with the corresponding alcohol oiler dem corresponding olefin.

(B) Regitz method: p-Toluenesulfonyl azide is reacted with the corresponding Acctoacetat and the 2-Diazoacetoacctai formed is deacetylated with a base to obtain diazoacclate (cf. Organic Syntheses, Coll. Vol. 5, P. 179).

(C) House's method: The acid chloride of p-toluenesulfonyihydrazone of glyoxylic acid chloride is reacted with the corresponding alcohol in the presence of a base (cf. for example Organic Syntheses, Coll. Vol. 5, p. 258).

The chiral Schiff base of the formula I given is synthesized by reacting a chiral amino alcohol of the following formula VI with salicylaldehyde of the following formula VII

where R means:

Methyl, dimethyl, l-adamanylodoxy / t-dimethyl / i- (methyl oxy) ethyl it is particularly effective for obtaining the formed alkylchrysium metal an excellent one optical purity and a high trans isomer content. This finding is very surprising due to the results of reactions in which a primary diazoacctal of a short-celtic aliphatic Alcohol of 1 to 8 carbon atoms, e.g. B. the ethyl ester is used (see. DE-OS 22 40 257).

To carry out the process according to the invention, an alkyl diazoacelate of the specified type is therefore reacted with 2,5-dimethyl-2,4-hexadiene using a chiral copper complex as a catalyst which is derived from an optically active Schiff base of the type specified in claim 1, / .. B. one with a monomeric structure according to the general formulas (III) or (IV) or one such R-

R ¹ C * HC OH

! I.

NH ₂ R ^J H

^{X /} OH

(Vl)

(VII)

wherein R ¹ and R ² have the meaning given in the main claim, where R ^{1 is} preferably a benzyl radical.

The usable oplisch active amino alcohols

ho of the given formula Vl are according to one of the the following two methods can be prepared, namely either by the fact that a racemic mixture of the corresponding amino alcohol is separated with a suitable separating agent, or by the fact that the

M amino alcohol from the implementation of an optically active Precursor compound is obtained. So z. B. an optically active amino ester of the following formula VIII with a Grignard reagent of the following Formula IX

an optically active amino alcohol of the formula VI while maintaining the configuralion:

R ²

¹ -C * H-C '() () R-' + R ² MgZ-R '-c * H -C-OH

I I I

(IX)

NH ₂ (VIII)

NHj R ¹
(Vl)

in which R ¹ and R ^{2 have} the meaning given and R ^{3 is} an alkyl radical having 1 to 10 carbon atoms or a benzyl radical and Z is a chlorine, bromine or iodine atom. Regarding the addition reaction of phenyl r. magnesium bromide on 1-alanine ethylsier see for example A. M c K e η ζ i c. R. Roger, GO W i 11 is, |. Chem. Soc, 779 (1926). and BM Ben jami π, H. |. S chaefer, CJ C ο 11 i π s, J. Am. Chem. Soc, 79, 6160 (1957).

With regard to the chiral copper complexes which can be used as catalysts according to the invention, are typical Suitable copper complexes of the formulas II, III and IV are those which differ from the following Chiral-Schiffs Derive bases:

N-salicylidene ^ -amino-1,1 -di (5-t-bulyl-

2-heptyloxyphenyl) -3- (phenyl) -1-propanol.
N-salicylidene-2-amino-1,1-di (5-l-butyl-

2-isopropoxy phenyl) -1-propanol,
N-salicylidene-2-amino-l, l-di (2-butoxy- ^{i (l}

5-t-butylphenyl) -1-propanol,
N-salicylidene-2-amino-l, 1-di (5-t-but> l-

2-octyloxy phenyl) -1 propanol.

As copper complexes of the optically active Schiffschen r. Bases of the formula I are copper complexes of the specified Compounds of formulas II, III and IV effective, the complex of the compound with the dimeric Structure of the formula II can be used in a particularly advantageous manner. The complex of the general formula II is synthesized by reacting a Schiff base of the general formula I with fVinem copper (II) salt, z. B. Copper (II) acetate.

The complex of the compound having the monomeric structure of the formula (IV) is synthesized by Implementation of the dimeric complex of formula (II) with a neutral monovalent ligand, e.g. B. pyridine, Picoline, or Lutidine The complex of the compound having the monomeric structure of Formula IiI is synthesized by reacting a copper complex of the w salicylaldehyde derivative of the formula VII with a Amino alcohol of the formula VI.

When practicing the process according to the invention, the reaction can be carried out independently of whether the chiral copper catalyst is soluble or insoluble in the reaction system.

The catalyst can be isolated and purified in a suitable manner for repeated use.

The molar ratio of copper complex to alkyl diazoacelate of the formula V is preferably in ^ Range from 0.001 to 0.1.

As a reaction temperature, a temperature from -50 to 150 ⁰ CAIS proves generally suitable. In the special cases where the reaction takes place at a temperature below the melting point of 2,5-dimethyl-2,4-hexadiene (15 ° C.), the addition of a suitable solvent to the reaction system may prove to be desirable. In these cases /. B. aromatic hydrocarbons, such as benzene, toluene and xylene, suitable as solvents.

The following examples are intended to explain the invention in more detail.

Usually there is an unambiguous relationship between the absolute configuration of those. Substance that induces asymmetry, and the absolute Configuration of the substance that induces the asymmetry. It is therefore also in the frame Needless to say in the present invention that when a copper complex of enantiomeric structure, which is opposite to that described in the following examples as a catalyst The alkylchrysan ihemate formed and the corresponding chrysanthemum monocarboxylic acid are also used have the opposite enantiomeric structure in question.

Bcis pi e ■ 1

0.03 g (0.2 iiifviu!) Of the dine K ^ picrkoinplcxcs before; (R) -N-Salicylidene 2-amino 1,1 di (5-i-butyl-2-ociyloxy) propanol (corresponding to the given formula (Ii). In which R ¹ = methyl, R ² = 5-l-butyl -2-octyioxyphenyl) dissolved in 17.6 g (16Ommol) of 2,5-dimethyl-2,4-hexadiene. A mixture of 4.4 g (40 mmol) of the specified diene and 4.5 g (20 mmol) of 1-menthyl-diazoacelal was added dropwise to the resulting solution over the course of 7 hours with stirring. At the beginning of the addition, the catalyst solution was heated once to 75.degree. C. to initiate decomposition of the diazoacetate, and the mixture was then kept at 40.degree. By the end of the addition, an almost quantitative amount of nitrogen gas had evolved.

The reaction mixture was used to isolate the excess unreacted diene (boiling point 45 ° C / 20mmHg) distilled under reduced pressure and there were 4.7 g of l-menthylchryspnthcnal in the form of an oil having a boiling point of 123 ° C / 0.2 mmHg. The based yield was 76% on the diazo compound.

The 1-menthyl ester was on a gas chromatography apparatus, which was equipped with a glass capillary column, analyzed to determine the composition of the optical isomers of chrysanthemum. the following results were obtained:

d-trans-Forni893 ⁰ / o,

l-trans form 2.7%,

Total amount of d-cis and I ice forms (one No further information was possible) 7.4%

The calculation showed that the percentage of trans isomers in the ester 93% and the optical purity the trans isomer was 94%.

A mixture of 42 g of I-methyl ester, 1.8 g of potassium hydroxide, 1.5 ml of water and 11 ml! Ethanol was heated to 100 ° C. for 7.5 hours with stirring. After the ethanol had been removed from the reaction mixture, the residue was diluted with water and extracted with ether. The aqueous alkaline solution was acidified with dilute sulfuric acid and then extracted with toluene. After the organic layer was washed with water and dried, toluene was distilled off under reduced pressure to obtain chrysanthemum monocarboxylic acid (2.4 g, yield 90%).

The chrysanthemum monocarboxylic acid was with

d-2-octanol reacted, and the diastereomers obtained were analyzed by gaschrorhalographis / ur determination of the optical isomers of chrysanthemum monocarboxylic acid, the following results being obtained:

d-trans form 90.4%. d-cis form 3.6%,

l-trans-form 4.7% l-cis-form 1.3%

The calculation showed that the optical purity of the trans isomers 90% and that of the cis isomers Was 50%.

Regarding the analysis of chrysanthemum monocrine acid, be /..B. referred to A. Mu ra no. Agr. Biol. Chem. 36, 2203 (1972).

Examples 2 to 6

Experiments similar to those described in Example I were carried out using the anaptjphpnpn rtimprpn Phiral- \ L nnfprl ^ rimnlp in Tahpllp i anaptjphpnpn rtimprpn.

xe and l-menthyl diazoate. The obtained results-

Table I.

Synthesis of 1-menthyl chrysanthemate

They are listed in Table I.

The content of iran isomers in 1-methyl chrysanthemate was determined by gas chromatography. The optical purity of the chrysanthemum monocarboxylic acid obtained after hydrolysis was determined by gas chromatographic analysis of the corresponding (S) -I-menthylheptyl ester.

It should be emphasized that when a catalyst of the (R) configuration is used, dextrorotatory chrysanthemum monocarboxylic acid is the preferred product, and when a catalyst of the (S) configuration is used, levorotatory chrysanthemum monocarboxylic acid is the preferred product.

Comparative example Λ
(GB-PS 7 40 014)

In the implementation between l-menthyl diazoacciat and 2,5-dimethyl-2,4-hexadiene was used as a catalyst instead of the chiral copper grain copper powder vprwpnrlpt Dip prhaltpnpn FrpphmvAp are in rlrr

Table I below is also listed.

E.g. Chiral copper complex (II) methyl R ² Reaction Chrysanlhcmat triins Optical clean Clv No. methyl temperature (M is called the acid
("■») methyl 5-t-butyl-2-oetyloxyphenyl Yield 72 trans 59 Configu- R ¹ Benzyl 5-t-butyl-2-isopropo.xyphen.v1 (C) C-) 70 60 2 ration Benzyl 5-t-Buty 1-2-butoxy phenyl 40 64 89 90 25th 3 (S) Copper powder 5-t-Buty! -2-heptyloxyphenyl 40 69 91 88 22nd 4th (S) 5-t-butyl-2-heptyloxy phenyl 60 67 75 87 5 (R) 40 42 76 86 0 6th (R) 40 36 86 Cf. (S) Examples 7 to 10 ^the He 123 69 0.7 in the bi Ex. A creation of l-menthy'-diazoacetate

Experiments similar to those described in Example 1 were carried out using the diazoacetates given in Table II and a chiral copper complex of the formula II with an (R) configuration, where R ¹ = methyl and R ² = 5-t-butyl-2- mean octyloxyphenyl. The results obtained are listed in Table II given below.

The content of trans isomers in the alkyl chrysanthemums was determined by gas chromatography. The optical purity of the ester after hydrolysis Chrysanthemum monocarboxylic acid obtained was determined by gas chromatography of the corresponding (S) -I-menthyl-1 -heptyl ester

The diazoacetates used in the examples were prepared according to one of the following Methods (A) or (B) prepared

According to method (A), a corresponding glycine ester is diazotized with isoamyl nitrite. The process can be represented by the following reaction scheme:

ROH - H ₂ NCH ₂ COOR - N ₂ CHCOOR

Game 11 is described as a typical example of this procedure.

According to method (B), the reaction takes place according to the following reaction scheme:

Diketen i!

RAW CH ₁ CCH ₂ COOR

corresp.
alcohol

Acetoacetate
O

Toluenesulfonyl azide

- CH ₃ CCCOOR

! I

\ -Diazoacetoacetate

Na methoxide

► N ₂ CHCOOR

Diazoacetate

Comparative example B

Using the same copper catalyst as in Examples 6 to 10, the reaction was carried out

9 10

carried out between ethyldiazcacetate and 2,5-dimethyl-2,4-hexadiene (DE-OS 24 07 094). The received Results are also shown in Table II below.

Table Il

Synthesis of alkyl chrysanthemates

E.g Diazoacetates synthesis Reaction Chrysanthemates trans Optical purity ice cream No. method temp. (%) Chrysanthemates, % R. A. Yield 81 trans 75 A. (C) (%) 89 - 7th cll-menthyl A. 40 67 84 90 46 8th d-neomenthyl N 65 77 79 87 45 9 i-adamantyl - 2} 82 51 85 62 10 (7,17-Dimethyl-yy- (1-methoxy) -; ithyl 40 80 86 V erg I. ethyl 40 54 68 Ex. B. (DE-OS 24 07 094)

The I-menthyl dia- / otate used as the starting material is obtained as follows:

A mixture of I-menthylglycine (19.7 g; 0.092 mol), Isoamyl nitrite (12.0 g; 0.10MoI) and acetic acid (1.6 g; 0.027 mol) in chloroform (400 ml) was stirred and refluxed for 25 minutes. That f.eaktionslösung was with In-sulfuric acid, then washed with a saturated aqueous solution of sodium bicarbonate and then with water. After drying the organic phase, the residue obtained by condensation (21 g) was purified by column chromatography (Silica gel 160 g, methylene chloride), using 1-menthyl diazoacetate (15.0 g, 73%) was obtained;

yellow crystals, [<x] n = -86.8 ° (chloroform, c = 1.0).

IR (F-ilm) v2l25cm- '

N MR (chloroform, tetramethylsilane (TMS)

(5 5.29 ppm

With regard to I-menthylglycine, see e.g. B. referred to K. H? wheel a. T. Hayakawa. Bull. Chem. Soc. lapan, 37, 191 (1964).

The surprising advantages that can be achieved according to the invention emerge from the following list, in that of the values for yield of trans compound and optical yield obtained in the above examples the corresponding values, as they can be achieved according to DE-OS 24 07 094, are compared.

E.g. trans (%) Optical yield d-trans (%) an trans (%) Λ B. C **) 1 93 94 90.2 η 2 *) 72 90 68.4 3 *) 70 88 65.8 4th 89 87 83.2 5 91 86 84.6 6 *) 75 86 69.8 40 7th 81 90 82.0 8th 89 87 83.2 9 84 85 77.7 10 79 86 73.5 DE-OS 51 68 42.8 4 ") 24 07 094

Remarks:

*) The values given are obtained when using the d-menthyl ester of diazoacetic acid and the asymmetric one Copper complex with (R) configuration; "IC = AX (0.5 + B / 200).

Claims (1)

Patent claims: I. Process for producing an optically active chrysanthemum monocarboxylic acid ester by reaction of 2,5-dimethyl-2,4-hexadiene with a Diazoacetate in the presence of an optically active copper complex, different from a base of the formula