NL8100220A - Novel unsaturated alcohols and their use in the preparation of oxolanes. - Google Patents

Description

. *

K HtgU WITH

Novel unsaturated alcohols and their uses in the preparation of oxolanes

The present invention relates to novel unsaturated alcohols and their use in the preparation of oxolanes.

In German Patent Application No. 1.7 ^ 9.97¼ and European Patent Application No. 0000002 states that some oxolane derivatives can be used as herbicides.

These oxolanes have the general formula: R5 R ^ R6 --- R3 9

Br R0 ^ R

Ar - CH - CE

Wherein the groups R to R have various meanings and Ar is an optionally substituted phenyl group. In British patent application no. 7900013 discusses similar oxolanes in which Ar is an optionally substituted, fully unsaturated ring containing 5 or 6 atoms in the ring, one of which is a nitrogen atom and the other are carbon atoms. For use as herbicides, the major compounds are generally those of the above formula, wherein R 1 is an optionally substituted alkyl group. These compounds can be prepared by an oxolane alcohol of the general formula: 8 1 00 2 2 0 * * 2 R5 R ^ é_ ^ 7 2

R '^ R

8/0

HO - CH TR

to react with a compound of the formula: f • Ar - CH - Hal in which Hal is a halogen atom.

However, the oxolane alcohols are quite difficult to prepare. A new class of olefinic alcohols has now been found which can be converted into the desired oxolane alcohols.

The invention therefore relates to a compound of the general formula: RT R5 R3 R1 8 * »» »2 R - CH = C - C - C - C - R (j)>>« 1 2 wherein R and R are independent of each other a hydrogen atom or an optionally substituted alkyl, cycloalkyl or aryl group 1 2 10 or R and R together represent an alkylene group; R3, R, R 'and R' independently represent a hydrogen atom or an optionally substituted alkyl, alkoxy or aryl group-7; R represents an optionally substituted alkyl group; 8 and R 0 represents a hydrogen atom or an optionally substituted alkyl-15 group.

The substituents which may optionally be present in the groups mentioned in this specification may be independently selected from, inter alia, halogen atoms, especially chlorine and fluorine atoms, and alkyl, alkoxy, alkoxyalkoxy, aryl and aryloxy groups. Alkyl, cycloalkyl, aryl, alkylene, alkoxy, alkoxyalkoxy and aryloxy- 8100220-f 3 groups preferably contain up to 8 carbon atoms. Preferred aryl and aryloxy groups are phenyl and phenoxy groups.

1 2

Independently of each other, R and R preferably represent a hydrogen atom, an alkyl group with at most 6 carbon atoms 1 2

or an optionally substituted phenyl group for, or R and R.

together represent an alkylene group having at most 6 carbon-12 atoms. R and R independently, but more preferably, represent a hydrogen atom, a methyl group or an ethyl-1 2 10 group, or R and R together form a pentamethylene group.

R 1, R 1, R 1, and R 1 independently of one another preferably represent a hydrogen atom or an alkyl or an alkoxy group of at most 6 carbon atoms which is optionally substituted by an alkoxy or alkoxyalkoxy group of at most 6 carbon atoms . Particular preference is given to compounds in which three of the 3-1 (.5 6 groups R, R, R and R represent hydrogen atoms and the fourth a hydrogen atom or a methoxy group optionally substituted by a methoxyethoxy group.

R 7 preferably represents an alkyl group having up to 6 carbon atoms which may be optionally substituted, especially a methyl, ethyl, halomethyl or methoxymethyl group.

O

R ° preferably represents a hydrogen atom.

As mentioned above, the compounds of general formula I can be cyclized to oxolane alcohols. The invention therefore also relates to a process for the preparation of a compound * of the general formula: R5 R ^ R ---- R3 (II) 7 2

r 'JBT

HO - CH R

8100220 r * k wherein R 1, R 2, R ^, r \ R ^, R ^, R ^ and R ^ have the "meanings" given for the general formula I, in which process a compound of the general formula I in reaction is applied with an electrophilic epoxidizer.

Suitable electrophilic epoxidizing agents are hydrogen peroxide, alkali metal peroxides or hypohalites, metal perborates, peroxyacetyl nitrate and silver oxide. Particularly suitable electrophilic epoxidizing agents are peroxyacids, for example aliphatic peroxyacids, such as peroxyacetic acid or peroxymic acid, or, preferably, aromatic peroxyacids such as unsubstituted or substituted peroxybenzoic acid. Halogen-substituted peroxybenzoic acids, for example acids in which the phenyl ring is substituted by one or two chlorine and / or bromine atoms, are particularly suitable. Meta-chloroperoxybenzoic acid is preferred.

The reaction is conveniently conducted in the presence of an inert solvent, for example, a liquid hydrocarbon, chlorinated hydrocarbon, ether or ester such as benzene, toluene, methylene chloride, carbon tetrachloride, diethyl ether or ethyl acetate. Mixtures of solvents can be used.

The reaction is preferably carried out at a temperature of from -10 to 80 ° C, in particular from 0 to 20 ° C. In some cases, it may be preferable to conduct the reaction at the reflux temperature of the solvent used.

The molar ratio of the compound of general formula I to the electrophilic epoxidizing agent is not critical. The compound of the general formula I and the electrophilic epoxidizing agent are preferably mixed in approximately equimolar amounts or using a slight excess of the epoxidizing agent. The molar ratio of the compound of the general formula I to the electrophilic epoxidizing agent is preferably between 1: 1 and 1: 2, in particular between 1: 1 and 1: 1.5. However, good yields can be obtained with a molar ratio of 1:10 or above.

8100220 4- t 5

The resulting compound of general formula II may be extracted from the reaction mixture, if desired, by any suitable work-up method. However, it may be advantageous to carry out a further chemical reaction using the compound of the general formula II after separation of this compound or directly in situ in the reaction mixture. In a preferred embodiment of the cyclization according to the invention, at least a part of the obtained compound of the general formula II is converted into an alkali metal or an alkaline earth metal metal salt thereof, and reacted with a compound of the general formula: R9

Ar - CH - Hal (lil) o wherein Hal represents a halogen atom, R represents a hydrogen atom or an optionally substituted alkyl group, and Ar represents an optionally substituted phenyl group or an optionally substituted, fully unsaturated heterocyclic group with 5 or 6 ring atoms, one of which is a nitrogen atom and the other are carbon atoms; from which reaction a compound is obtained having the general formula: R5 R6 --- R3 (IV) r "L ^ <R2 R9 R8

Ar - CH - o \ h 'R1 1 9 in which R to R and Ar have the above meanings.

R 20 preferably represents a hydrogen atom.

Ar is preferably unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, especially chlorine or fluorine atoms, and alkyl groups having up to 6 carbon atoms, especially 25 methyl or ethyl groups. For example, Ar may represent an optionally substituted 8100220 6 < phenyl group, especially an unsubstituted phenyl group or a 2-methyl, 2-fluoro, 2-chloro or 2,6-dichloro-phenyl group.

Optionally substituted, fully unsaturated hetero-5 cyclic groups are to include optionally substituted pyridyl, pyrrolyl and azacyclopentadienyl groups.

For example, group Ar can propose one of the following groups:

CH

O <y

If Ar represents a heterocyclic group, this group is preferably bonded to the rest of the molecule with a carbon atom, and the ring nitrogen atom is preferably adjacent to this carbon atom. For example, Ar may represent a 2-pyridyl group which may be substituted in the 3 or β position by a chlorine or fluorine atom or by a methyl or ethyl group.

The reaction between the salt of the compound of the general formula II and the compound of the general formula III is most preferably carried out without the compound of the general formula II being separated from the reaction mixture generated by the cyclization reaction, or by reaction of the crude product obtained by evaporating the solvent from said reaction mixture.

The oxolane alcohol of the formula II can be converted into a salt thereof by reaction with a base. Alkali metal hydroxides, alkoxides or hydrides are suitable bases. The alcohol can be converted into its salt before the alcohol is mixed with the compound of formula III, or the salt can be obtained in situ by mixing the compounds of formulas II and III in the presence of a base. Any suitable solvent, for example an aromatic hydrocarbon, such as benzene or toluene, can be used for the reaction. For example, the reaction may be carried out at 8100220 τ "at a temperature of 50-150 ° C. The reaction is" preferably carried out "at the reflux temperature of the solvent used.

The compounds of the general formula I can be prepared according to methods which are similar to those known in the art. The correct method obviously depends on the desired meaning 1 8 of. the substituents R to R. Three suitable methods are mentioned below: 1. In a method with which. very good results are obtained when at least one of the groups R and R hydrogen 1 2 xs and R and R neither represent hydrogen, or 12 3 b when all groups R, R, R and R are hydrogen, but which method is generally unsuitable when one 3b of the groups R and R represents alkoxy, an epoxide of the general formula: R 1 N'N'vR 1 is reacted with a Grignard reactant of the general formula: RT R5 R8 - C12 = C - C - MgHal (Vl) έ6 where Hal is a chlorine, bromine or iodine atom, under the usual conditions required when using Grignard reactants.

2. In a method of preparing compounds in which at least one of at least one of R and R groups is not a hydrogen atom, a compound of the general formula: 7 5 3 R1 R ^ RJ 0 8 i i il R-CH = CCCCX (VII)

f I

8100220 2.

8> * <where X has the same "meaning as R m of the general formula X, or X represents an alkoxy group, attempted in reaction with a Grignard reaction component of the general formula: R 1 MgHal (VIII) wherein Hal is a chlorine, chromium - or iodine atom and 1 5 R, with the exception of a hydrogen atom, has the meaning given for the general formula I. If X represents an alkoxy group, a compound with the general form 2. 1 mule I in which R has the same "meaning as R, since the alkoxy group X disappears from the molecule when two groups R * 'are added.

3. In order to prepare compounds of the general formula I in which both R and R represent hydrogen atoms, an ester of the formula VII, wherein X is an alkoxy group, can be reacted with a selective reducing agent, eg lithium aluminum hydride.

A compound of the general formula I can be most suitably prepared in some cases by first preparing a corresponding compound in which one of the groups R-R 4 has a different meaning than desired, after which said group is added to the desired group converted.

The invention is further illustrated in the following Examples. The reported IMR values refer to tetramethylsilane in CDCl 4.

EXAMPLE I - The preparation of 2-ethyl-h-methoxyethoxymethoxy-5-hydroxy-5-methyl-hex-1-en-ch 2 - o - (ch 2) 2 - o - ch 3 c 2 h 5 o ch 3

CH = C-CH_-CH-C-CH

^ r J

OH

(A) 5 * 9 g sodium was dissolved in 300 ml absolute ethanol and ethyl acetoacetate (31.72 g) was added. The mixture was stirred for 15 minutes, 2-bromomethylbut-1-one (bo g) was added 8100220 -> # over 30 minutes, then the mixture was refluxed for 2 hours. The mixture was then poured onto brine, extracted several times with diethyl ether, washed with brine, dried and evaporated. Distillation of the residue in vacuo gave 29 g, corresponding to a yield of 60%, of 2-ethyl-ii-methylcarbonyl-ethoxycarbonylbut-1-boiling 120-127 ° C at a pressure of 10 mm Hg , obtained.

(b) The product of (a) (25 g) was added to 6.2 g of a 50 µl solution of sodium hydride in oil dissolved in benzene (250 ml) and stirred for 2 hours. Dibenzoyl peroxide (CgHj-COg) (20 µg) in benzene (200 ml) was added over 30 minutes. The mixture was stirred for an additional 2 hours and then poured into water, extracted several times with diethyl ether, dried and distilled in vacuo to give 2k g, corresponding to a yield in step (b) of 89.5%, 2-ethyl-k -Methylcarbonyl-ethoxycarbonyl-U-benzoyloxybut-1-ene, boiling at 160 ° C at a pressure of 1 mm Hg, was obtained.

(C) Sodium (250 mg) was dissolved in dry ethanol (250 ml) and the product of (b) (22.65 g) was added. The mixture was stirred overnight and then refluxed for 2 hours. Ammonium chloride (0.5 g) and water (0.25 ml) were added, followed by stirring for another half hour. The mixture was then filtered and the solvent was diluted. The residue was dissolved in diethyl ether, the mixture was filtered and the ether was evaporated, yielding 2-ethyl-1-hydroxy-1-ethoxycarbonylbut-1-one which was identified by magnetic nuclear spin resonance. This residue was dissolved in methylene chloride (200 ml) containing methoxyethoxymethyl chloride (12.5 ml) and ethylldisopropylamine (22.5 nil) and the mixture was stirred overnight. An additional 5 nil methoxyethoxymethyl chloride and 8100220 were added

- *> V

10 ml of ethyl diisopropylamine are added. The mixture was refluxed for 3 hours and then poured into water, washed with 1% hydrochloric acid and then brine, dried over potassium carbonate and evaporated. The residue was eluted in a silica gel column with methylene chloride. The solvent was then evaporated and the product was distilled. An amount of 1U, 5 g of 2-ethyl-U-methoxyethoxymethoxy-ethoxycarbonyl-hut-1-one with a boiling point of 158-162 ° C and a pressure of 12 mm Hg was obtained.

(d) Magnesium (3.3 g) was dissolved in a solution of methyl iodide (19.1 g) in diethyl ether, and an ether solution of 1U g of the ester prepared in c) was refluxed for 20 minutes. added. The mixture was then stirred for an additional 2 hours. Saturated ammonium chloride solution was then added, the mixture was extracted with diethyl ether, washed with brine, dried over magnesium sulfate and evaporated. The residue was distilled to obtain 9.5 g of the desired compound boiling at 115-120 ° C at a pressure of 2 mm Hg. The HMR spectrum was as follows: 0.9 (3H, triplet); 1.2 (6H, singlet); 1.8-2.3 (UH, complex) 3.2 (1H, wide); 3.3 (3H, singlet); 3.5 (5H, complex); h, J (Uh, complex).

EXAMPLE II - The preparation of 2,2-dimethyl-3-methoxyethoxymethoxy-5-hydroxymethyl-5-ethyloxolane_

The olefinic alcohol (9.5 g) prepared in Example I was dissolved in methylene chloride and added to m-chloroperoxybenzoic acid (8.65 g of 85% pure material) in methylene chloride at 0 ° C for 30 minutes. The mixture was stirred for 20 hours and then washed successively with aqueous solutions of sodium sulfite, sodium bicarbonate and sodium chloride and dried. The solvent was evaporated to yield a crude product which was identified by magnetic nuclear magnetic resonance as a mixture of isomers of the desired product. The spectrum was as follows: 0.9 (3H, triplet); 8100220 - * © 11 1.2 (βΗ, doublet); 1.5-2.5 (5H, complex); 3.3 (3H, singlet); 3.11-1.1 (TH, complex); 4.7 (2H, singlet). The product was reacted without further purification as described in Example III.

EXAMPLE III - The "Preparation of 2,2-dimethyl-3-methoxyethoxy-methoxy-5-benzyloxymethyl-5-ethyloxolane"

The entire amount of the crude product obtained in Example II was dissolved in toluene (80 ml) and added with stirring for 15 minutes to a solution of sodium hydride (2.15 g of a 50% suspension in oil) in dry toluene (150 ml).

The mixture was refluxed for 10 minutes and then henzyl bromide (8.25 g) in toluene (50 ml) was added dropwise. Reflux and stirring were continued for an additional 18 hours. The mixture was then poured onto brine, extracted with diethyl ether and dried over magnesium sulfate. The solvent was removed to obtain 17.5 g of crude material which was purified in a silica gel column using acetone / henzine as an eluent to yield 8.2 g of the pure desired product. Magnetic nuclear magnetic resonance showed that a mixture of geometric isomers was present.

Magnetic nuclear magnetic resonance 0.9 (3H, triplet); 1.2 (6H, doublet); 1.4-2.4 (4h, complex); 3.3 (3H, singlet); 3.5 (6H, complex); 4.1 (1H, wide triplet); 4.5 (2H, singlet); 4.7 (2H, singlet); 7.2 (5H, singlet).

25 Elemental analysis CH

Calculated for c20 ^ 32 ^ 5 68.15 9.5

Found 67.5 9.7 EXAMPLE IV - 2-Methyl-4-methoxyethoxymethoxy-5-hydroxy-5-methylhex-1-ene_

This compound was prepared by a method similar to that described in Example I, using 2-bromomethylpropylene as a starting material.

8100220 * 12

Magnetic nuclear magnetic resonance 1.1 (6h, singlet); 1.7 (3H, saturated singlet); 2.2 (2H, complex); 3.3 (3H, singlet); 3.5 (HH, complex); U, 7 (^ H, hreed doublet).

EXAMPLE V - 2,2-Dimethyl-3-methoxyethoxymethoxy-5-henzyloxy-methyl-5-methyloxolane-5 This compound was prepared according to a method similar to that described in Example II, using the compound of Example IV as starting material used. Magnetic nuclear magnetic resonance showed that the product was a mixture of geometric isomers.

10 Magnetic nuclear magnetic resonance 1.2 (9H, singlet); 1.5-2.5 (2H, complex); 2.3 (3H, singlet); 3. U (6h, complex); 3.9 (1H, wide triplet); (2H, singlet); kt6 (2H, broad singlet); 7.2 (5H, singlet).

Elemental analysis e C H

15 Calculated for C ^ H ^ qO ^ 6j, b 8.9 ^

Found 67.9.3 EXAMPLE VI - The preparation of 2-ethyl-5-hydroxy-5-spirocyclo-hexyl-pent-1-en-1

0H2 «C - CH2 - CH2 - c J

3.21 g of magnesium were added to 75 ml of diethyl ether and the mixture was cooled to 0 ° C. In a nitrogen atmosphere, 2-bromomethylbut-1-ene (13.3 g) in diethyl ether (50 ml) was added over 3 hours. The cooling bath was then removed and stirred for an additional hour. Methylene cyclohexane oxide (5 g) in diethyl ether (25 ml) was added over 20 minutes and stirred for another 30 minutes. The mixture was then poured into aqueous ammonium chloride and the organic phase separated, washed with brine, dried over sodium sulfate and evaporated. The residue was distilled under reduced pressure to give 11.18 g of a crude product which was treated with 8 1 0 0 2 2 0 13. - was purified by chromatography using 2f acetone in gasoline as the eluent. 7.85 g of the desired product, corresponding to a yield of 81%, were obtained. The MMR spectrum was as follows: 1.0 (3H, triplet); 1.5 (12H, broad singlet); 2.0 (5H, complex); k, 6 (2H, broad singlet).

EXAMPLE VII - The preparation of 2-spirocyclohexyl-5-hydroxy-methyl-5-ethyloxolane_

The olefinic alcohol (5 5 g) prepared in Example 6 was dissolved in methylene chloride (20 ml) and added dropwise at 0 ° C to m-chloroperoxybenzoic acid (6.5 g) in methylene chloride (120 ml). The mixture was allowed to stand at room temperature overnight, after which it was filtered, washed successively with brine containing sodium sulfite, with aqueous sodium carbonate and brine, dried over magnesium sulfate and evaporated. The residue was distilled to obtain 5-6 g of the desired product, boiling at 85-86 ° C, at a pressure of 0.9 mm Hg.

EXAMPLE VIII - The preparation of 2-ethyl-5-hydroxy-5-ethyl-hent-1-en-1

COH OH

t2 5, CH2 = C-CH2-CH2-C-C2H5

The procedure described in Example VI was repeated, but the epoxide was replaced with: / \ (02H5) 2 O-CHg

The desired compound was obtained in a yield of "88.6% and had the following HMR spectrum: 1.0 (10H, multiplet); 1.6 (6H, multiplet); 2.0 (kH, multiplet); ^ 7 (2H, broad singlet).

25 Elemental analysis C H

Calculated for C 7 H 7 O 77.6 13.02

Found J6, k 13.2 8100220 1¼> EXAMPLE IX - The Preparation of 2,2-diethyl-5-hydroxymethyl-5-ethyloxolane__

The procedure described in Example VII was repeated using the product of Example VIII as the starting material. The product was obtained with a yield of 5 80.5 *.

EXAMPLE X - The preparation of 2-ethyl-3-methoxyethoxymethoxy-5-hydroxy-5-itethylethyl-1-en-1

Magnesium (2.36 g) was dissolved in 120 ml diethyl ether containing methyl iodide (6.2 ml). 2-Ethyl-3-methoxyethoxymethoxy-U-ethoxycarbonylbut-1-en (9.8¼ g) dissolved in 20 ml diethyl ether 10 was added dropwise over 20 minutes at such a rate that the material refluxed gently. A heavy, oily precipitate was separated. An excess of saturated ammonium chloride solution was added, the mixture was extracted with diethyl ether, washed with brine, dried over magnesium sulfate and evaporated. The crude product was purified in a silica gel column using 5% acetone in gasoline as the eluent. 7.5 g of the desired product were obtained.

Magnetic nuclear magnetic resonance 1.1 (3H, triplet); ί, 3 (6H, doublet); 1.6-2.2 (1 + H, complex); 3.3 (3H, singlet); 3.15 (5H, complex); U.5 (1H, multiplet); ks6 (2H, broad singlet); k.9 ("IS, broad singlet); 5.0 (1H, broad singlet).

8100220

Claims (13)

1. Compound of the general formula: R7 R5 R3 R1 Q 1 tt I p R-CH = C-C-C-CR (I) '6' RR OH 12 wherein R and R independently of each other is a hydrogen atom or an optionally substituted alkyl, cycloalkyl or aryl group 1 2 representing either R and R together represent an alkylene group; The groups R 3, R 4, R 4 and R 4 independently represent a hydrogen atom or an optionally substituted alkyl, alkoxy or aryl group; R represents an optionally substituted alkyl-Q group; and R 0 represents a hydrogen atom or an optionally substituted alkyl group. A compound according to claim 1, characterized in that R 2 and R independently represent a hydrogen atom or an alkyl green with at most 6 carbon atoms or an optionally substituted phenyl group, or R and R together represent an alkylene group with up to 6 carbon atoms. A compound according to claim 2, characterized in that R 2 and R independently represent a hydrogen atom, a methyl 1 2 group or an ethyl group, or R and R together represent a pentamethylene group. 4. A compound according to any one of claims 1-3, characterized in that R3, r'R '* and R'independently represent a hydrogen atom or an alkyl or alkoxy group with at most 6 carbon atoms which is optionally substituted by a alkoxy or alkoxyalkoxy group with up to 6 carbon atoms. 5. A compound according to any one of claims 1-t, characterized in that R represents a methyl, ethyl, halomethyl or methoxymethyl group. 8 1 0 0 2 2 0 * m Compound according to any one of claims 1-U, characterized in that Q represents R a hydrogen atom. 7. Process for preparing a compound of the general formula: R- -R ^ R6 --- R3 (II) RT r2 R8 HO ^ CH Έ1 12 3 ^ 5 6 7 8 5 wherein R, R, R, R, R, R, R and R have the meanings mentioned for the general formula I, characterized in that a compound of the general formula I is reacted with an electrophilic epoxidizing agent. 8. Process according to claim 7, characterized in that the epoxidizing agent is an aliphatic or aromatic peroxyacid. Process according to claim 8, characterized in that the epoxidizing agent is meta-chloroperoxybenzoic acid. 10. A method according to any one of claims 7-9, characterized in that the method is carried out at a temperature of -10 to 80 ° C. Process according to any one of claims 7-10, characterized in that the molar ratio of the compound of the general formula I to the epoxidizing agent is between 1: 1 and 1: 2. 12. Process according to any one of claims 7-11 », characterized in that the process comprises a further step in which at least a part of the obtained compound of the general formula II is converted into an alkali metal or an alkaline earth metal salt thereof and is reacted charged with a compound of the general formula: R9 Ar CH - Hal (lil) 8100220 9 _5S wherein Kal represents a halogen atom, R represents a hydrogen atom or an optionally substituted alkyl group, and Ar represents an optionally substituted phenyl group or an optionally substituted whole unsaturated ring with 5 or 6 carbon-5 atoms in the ring, one of which is a nitrogen atom and the other carbon atoms; whereby a compound of the following general formula is obtained: F * Bk R6 --- R3 (IV) r "[^ r2 R9 R8 Ar - CH - 0 - ΌΗ R 1 9 in which R to R and Ar have the above meanings . 13. A compound of the formula II prepared by a process according to any one of claims 7-11. lU. Compound of formula IV prepared by a method according to claim 12. 8100220