GB2067561A

GB2067561A - Unsaturated alcohols and their use in the preparation of oxolanes

Info

Publication number: GB2067561A
Application number: GB8101557A
Authority: GB
Original assignee: Shell Internationale Research Maatschappij BV
Current assignee: Shell Internationale Research Maatschappij BV
Priority date: 1980-01-21
Filing date: 1981-01-19
Publication date: 1981-07-30
Also published as: GB2067561B

Abstract

Novel compounds of the general formula <IMAGE> in which each of R<1> and R<2> independently represents a hydrogen atom or an optionally-substituted alkyl, cycloalkyl or aryl group, or R<1> and R<2> together represent an alkylene group; each of R<3> R<4>, R<5> and R<6> independently represents a hydrogen atom or an optionally-substituted alkyl, alkoxy or aryl group; R<7> represents an optionally-substituted alkyl group; and R<8> represents a hydrogen atom or an optionally-substituted alkyl group, may be cyclised to form an oxolane of the general formula <IMAGE> The oxolanes (II) are useful in the preparation of herbicidally active compounds.

Description

SPECIFICATION Novel unsaturated alcohols and their use in the preparation of oxolanes This invention relates to novel unsaturated alcohols and their use in the preparation of oxolanes.

German Offenlegungsschrift No. 2749974 and European Patent Application No. 0000002, disclose that certain oxolane derivatives are useful as herbicides.

Such oxolanes have the general formula

where the groups R' to R9 have various meanings, and Ar is an optionally substituted phenyl group. UK Patent Application No. 7900613 discloses similar oxolanes in which Ar is an optionally substituted fully unsaturated ring having 5 or 6 atoms in the ring of which one is a nitrogen atom and the remainder are carbon atoms. Generally, the most interesting compounds for use as herbicides are those compounds of the above formula in which R7 is an optionally substituted alkyl group. Such compounds can be prepared by reacting an oxolane alcohol of the general formula

with a compound of formula

where Hal is a halogen atom.

The oxolane alcohols are however rather difficult to synthesise. A novel class of olefinic alcohols which can be converted into the desired oxolane alcohols has now been found.

Therefore the invention provides a compound of the general formula

wherein each of R' and R2 independently represents a hydrogen atom or an optionallysubstituted alkyl, cycloalkyl or aryl group, or R1 and R2 together represent an alkylene group; each of R3, R4, R5 and R6 independently represents a hydrogen atom or an optionally-substituted alkyl. alkoxy or aryl group; R7 7 represents an optionally-substituted alkyl group; and P8 represents a hydrogen atom or an optionally-substituted alkyl group.

The optional substituents in an optionally-substituted group referred to in this specification may for example be one or more substituents independently selected from halogen atoms, especially chlorine and fluorine atoms, and alkyl, alkoxy, alkoxyalkoxy, aryl and aryloxy groups.

Alkyl. cycloalkyl, aryl, alkylene, alkoxy, alkoxyalkoxy and aryloxy groups preferably each contain up to 8 carbon atoms. The preferred aryl and aryloxy groups are phenyl and phenoxy groups.

Preferably each of R' and P2 independently represents a hydrogen atom, an alkyl group having up to 6 carbon atoms, or an optionally substituted phenyl group, or R1 and R2 together represent an aikylene group having up to 6 carbon atoms. More preferably, each of R1 and R2 independently represents a hydrogen atom, a methyl group or an ethyl group, or R' and R2 together represent a pentamethylene group.

Preferably each of R3. R4, R5 and R6 independently represents a hydrogen atom or an alkyl or an alkoxy group having up to 6 carbon atoms optionally substituted by an alkoxy or alkoxyalkoxy group having up to 6 carbon atoms. More preferably, three of R3, R4, R5 and P6 represent hydrogen atoms and the fourth represents a hydrogen atom or a methoxy group optionally substituted by a methoxyethoxy group.

Preferably R7 represents an alkyl group having up to 6 carbon atoms which may be unsubstituted or substituted. More preferably R7 represents a methyl, ethyl, halomethyl or methoxymethyl group.

Preferably Ra represents a hydrogen atom.

As stated above, the compounds of the general formula I can be cyclised to form oxolane alcohols. The invention therefore also provides a process for the preparation of a compound of the general formula

in which K'. R:, R:. Rl. R5, R6, R7 and Re have the meanings given for the general formula I, which comprises reacting a compound of the general formula I with an electrophilic epoxidising agent.

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

The reaction is suitably carried out 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 may be employed.

The reaction is preferably carried out at a temperature in the range of from - 1 0'C to 80'C, especially 0 to 20 C. It may in some cases be convenient to carry out the reaction at the reflux temperature of the solvent used.

The molar ratio of the compound of the general formula I and the electrophilic epoxidising agent is not of critical importance. Preferably the compound of the general formula I and the electro-philic epoxidising agent are mixed in approximately equimolar quantities, or a slight excess of the epoxidising agent is used. Preferably the molar ratio of the compound of the general formula I to the electrophilic epoxidising agent is in the range of from 1:1 to 1:2 especially 1:1 to 1:1.5. Useful yields can however be obtained using a molar ratio of up to 1:10 or higher.

If desired, the resulting compound of the general formula II may be extracted from the reaction mixture by any suitable work-up procedure. However, it may be advantageous to carry out a further chemical reaction using the compound of the general formula II either after its isolation or directly in situ in the reaction mixture. In a preferred embodiment of the cyclisation process according to the invention, at least p3rt of the resulting compound of the general formula Il is converted into an alkali metal or alkaline earth metal salt thereof, and reacted with a compound of the general formula R9 Ar-CH-Hal (III) in which Hal represents a halogen atom, R9 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 having 5 or 6 ring atoms of which one is a nitrogen atom and the remainder are carbon atoms; to give a compound of the general formula

in which R' to R9 and Ar have the meanings given above.

Preferably Ar is unsubstituted or is 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 methyl or ethyl groups. For example Ar may represent an optionally substituted phenyl group, especially an unsubstituted phenyl group or a 2-methyl-, 2-fluoro-, 2-chloro, or 2,6-dichloro-phenyl group.

By optionally-substituted fully unsaturated heterocyclic groups there should be understood optionally-substituted pyridyl, pyrrolyl and azacyclopentadienyl groups. Thus the group Ar may for example represent one of the groups:

If Ar represents a heterocyclic group, this group is preferably bonded to the rest of the molecule through a carbon atom, and the nitrogen atom in the ring is preferably adjacent to this carbon atom. For example, Ar may represent a 2-pyridyl group which is unsubstituted or substituted in the 3 or 6 position by a chlorine or fluorine atom or by a methyl or ethyl group.

Reaction of the salt of the compound of the general formula II with the compound of the general formula Ill is most conveniently carried out either without isolation of the compound of the general formula II from the reaction mixture resulting from the cyclisation reaction, or by reaction of the crude product resulting from evaporation of the solvent from said reaction mixture.

The oxolane alcohol of formula Il may be converted into a salt thereof by reaction with a base.

Alkali metal hydroxides, alkoxides or hydrides are suitable bases. The alcohol may be converted into its salt prior to admixing it with the compound of formula Ill, or the salt may be formed in situ by admixing the compounds of the formulae II and III in the presence of a base. Any suitable solvent may be used for the reaction, for example an aromatic hydrocarbon such as benzene or toluene. The reaction may for example be carried out at a temperature in the range of from 50 to 1 50 C. Conveniently, the reaction is carried out at the reflux temperature of the solvent used.

The compounds of the general formula I may be prepared by methods analogous to known methods. The precise method chosen will of course depend on the desired meanings of the substituents R1 to R8. Three suitable methods are as follows.

1. A method which proceeds most satisfactorily when at least one of R3 and R4 is hydrogen and Rl and R2 are other than hydrogen, or when all of R', R2, R3 and R4 are hydrogen, and which is generally not suitable when one of R3 and R4 is alkoxy, involves the reaction of an epoxide of the general formula

with a Grignard reagent of the general formula

where Hal is a chlorine. bromine or iodine atom, under the usual conditions necessary when using Grignard reagents.

2. A method of preparing compounds in which at least one of R' and R2 is other than a hydrogen atom involves the reaction of a compound of the general formula

R' R; in which X has the same meaning as the symbol R;' in the general formula I, or X is an alkoxy group, with a Grignard reagent of the general formula R1MgHal (VEIL) in which Hal represents a chlorine, bromine or iodine atom and R' has the meaning given for the general formula I with the exception of a hydrogen atom. If X represents an alkoxy group, a compound of general formula I is produced in which R2 has the same meaning as R', since the alkoxy group X is lost from the molecule as two groups R1 are added.

3. In order to prepare compounds of the general formula I in which both R' and R2 represent hydrogen atoms, an ester of formula VII in which X is an alkoxy group may be reacted with a selective reducing agent, for example lithium aluminium hydride.

It may in some cases be most convenient to prepare a compound of the general formula I by first preparing a corresponding compound in which one of the groups R'-RB has a different meaning from that desired, and subsequently converting said group into the desired group.

The following Examples illustrate the invention. NMR values given are values relative to tetramethylsilane in CDCI3.

Example 1 Preparation of 2-eth yl-4-m ethoxyeth oxym eth oxy-5-h ydroxy-5-m eth yl-h ex- ? -en e

(a) 5.9 g sodium were dissolved in 300 ml absolute ethanol and ethyl acetoacetate (31.729) was added. The mixture was stirred for 15 minutes, 2-bromomethylbut-1-ene (40 g) was added over 30 minutes, and the mixture was then refluxed for 2 hours. The mixture was then poured onto brine, extracted several times with diethyl ether, washed with brine, dried and evaporated down. Distillation of the residue under vacuum gave 29 g, corresponding to a 60% yield, of 2 ethyl-4-methylcarbonyl-4-etho;r arbonylbut-1 -ene, boiling point 1 20-1 27 'C at a pressure of 10 mm Hg.

(b) The product from .'-') (25 91 was added to 6.2 g of a 50% solution of sodium hydride in oil dissolved in benzene (250 ml) and stirred for two hours. Dibenzoyl peroxide, (C6H5CO2)2, (20.4 9) in benzene (200 mij was added over 30 minutes. The mixture was stirred for a further 2 hours, and then poured onto water and extracted several times with diethyl ether, dried, and distilled under vacuum to give 24 g, corresponding to a yield in step (b) of 89.5%, of 2-ethyl-4 methylcarbonyl-4-ethoxyearbonyl-4-benzoyloxybut-1-ene, boiling point 1609C at a pressure of 1 mm Hg.

(c) Sodium (250 mg) was dissolved in dry ethanol (250 ml) and the product from (b) above (22.65 9) 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 and stirring was continued for hour. The mixture was then filtered and the solvent was evaporated. The residue was dissolved in diethyl ether, the mixture was filtered and the ether evaporated off to leave 2-ethyl-4-hydroxy 4-ethoxy-carbonylbut-1-ene which was identified by NMR. This residue was dissolved in methylene chloride (200 ml) containing methoxyethoxymethyl chloride (12.5 ml) and ethyl diisopropylamine (22.5 ml) and the mixture was stirred overnight. A further 5 ml methoxyethoxymethyl chloride and 10 ml ethyl diisopropylamine were added. The mixture was refluxed for 3 hours and then poured onto water, washed with 10% hydrochloric acid and then brine, dried over potassium carbonate and evaporated down.The residue was eluted down a silica gel column using methylene chloride. The solvent was then evaporated and the product was distilled. 14.5 g of 2-ethyl-4-methoxyethoxymethoxy-4 ethoxycarbonyl-but-1-ene, -ene, boiling point 158-162"C at a pressure of 12 mm Hg, were obtained.

(d) Magnesium (3.3 g) was dissolved in a solution of methyl iodide (19.1 g) in diethyl ether, and an ethereal solution of 1 4 g of the ester prepared in (c) above was added to the refluxing solution over 20 minutes. The mixture was then stirred for a further 2 hours. Saturated ammonium chloride solution was then added, the mixture was extracted with diethyl ether, washed with brine, dried over magnesium sulphate and evaporated down. The residue was distilled to obtain 9.5 g of the title compound, boiling at 115-120 C at a pressure of 2 mm Hg. Its NMR spectrum was as follows: 0.9(3H,triplet); 1.2(6H,singlet); 1.8-2.3(4H,complex) 3.2(1H,broad); 3.3(3H,singlet); 3.5(5H,complex); 4.7(4H,complex).

Example 2 Preparation of 2, 2-dimeth yl-3-m eth oxyethoxymerhoxy- 5-h ydroxym ethyl- 5-eth yloxolan e The olefinic alcohol prepared in Example 1(9.5 g) was dissolved in methylene chloride and added to tmchloroperoxybenzoic acid (8.65 g of 85% pure material) in methylene chloride at 0 C over 30 minutes. The mixture was stirred for 20 hours, and then washed successively with aqueous solutions of sodium sulphite, sodium bicarbonate and sodium chloride, and dried. The solvent was evaporated to leave a crude product which was identified as a mixture of isomers of the desired product using NMR, as follows: 0.9(3H,triplet); 1 .2(6H,doublet); 1.4-2.5(5H,complex); 3.3(3H,singlet); 3.4-4.1 (7H,complex); 4.7(2H,singlet).The product was reacted without further purification as described in Example 3.

Example 3 Preparation of 2,2-dimethyl-3-methoxwethoxymethoxy-5-benzyloxymethyl-5-ethyloXolane The whole of the crude product obtained in Example 2 was dissolved in toluene (80 ml) and was added with stirring to a solution of sodium hydride (2.1 5 g of a 50% suspension in oil) in dry toluene (150 ml) over 1 5 minutes.

The mixture was refluxed for 40 minutes, and benzyl bromide (8.25 g) in toluene (50 ml) was then added dropwise. Refluxing and stirring was continued for 1 8 hours. The mixture was then poured onto brine, extracted with diethyl ether and dried over magnesium sulphate. The solvent was removed to give 1 7.5 g of crude material, which was purified on a silica gel column using acetone/petrol as eluant, to give 8.2 g of the pure desired product. NMR showed that a mixture of geometric isomers was present.

NMR Q.9(3H,triplet): 1.2(6H,doublet); 1 .4-2.4(4H,complex); 3.3(3H,singlet); 3.5(6H,complex); 4.1(1 H,broad triplet); 4. 5(2H,singlet); 4.7(2H,singlet): 7.2(5H,singlet) Elemental Analysis C H Calculated for QoH320s 68.15 9.5 Found 67.5 9.7 Example 4 2-Methyl-4-methoxyethoxymethoxy-5-hydroxy-5-methylhex- 1-ene The title compound was prepared by a method analogous to that described in Example 1, using 2-bromomethylpropene as starting material.

NMR 1.1 (6H,singlet); 1.7(311,broad singlet); 2.2(2H.complex). 3.3(3H,singlet); 3.5(6H,complex); 4.7(4H.broad doublet).

Example 5 2, 2-Dimethyl-3-methoxymethoxymethoxy-5-benzyloxymethyl-5-methyloXolane The title compound was prepared by a method analogous to that described in Example 2 using the compound of Example 4 as starting material. NMR showed the product to be a mixture of geometric isomers.

NMR 1.2(9H,singlet); 1 .5-2.5(2H,complex); 2.3(3H,singlet); 3.4(6H,complex); 3.9(1 H,broad triplet); 4.4(2H,singlet); 4.6(2H,broad singlet); 7.2(5H,singlet).

Elemental Analysis C H Calculated for C19H30O5 67.4 8.94 Found 67.4 9.3 Example 6 Preparation of 2-ethyl-5-hydroxy-5-spirocyclohexyl-pent -ene

3.21 g magnesium were added to 75 ml diethyl ether and cooled to O'C. Under an atmosphere of nitrogen, 2-bromomethylbut-1-ene (13.3 g) in diethyl ether (50 ml) was added over 3 hours.

The cooling bath was then removed and stirring was continued for a further hour. Methylenecyclohexane oxide (5 g) in diethyl ether (25 ml) was added over 20 minutes and stirring was continued for a further 30 minutes. The mixture was then poured onto aqueous ammonium chloride, and the organic phase was separated, washed with brine, dried over sodium sulphate and evaporated down. The residue was distilled under reduced pressure to give 11.18 g of a crude product which was purified by chromatography using 2% acetone in petrol as eluent.

7.85 g of the desired product, corresponding to an 81% yield, were obtained. Its NMR spectrum is as follows: 1 .0(3H.triplet); 1.5(12H.broad singlet); 2.0(5H,complex); 4.6(2H,broad singlet).

Example 7 Preparation of 2-spirocycloh exyl-5-h ydroxym e th yl-5-eth yloxolane The olefinic alcohol prepared in Example 6 (5.5 g) was dissolved in methylene chloride (20 ml) and added dropwise to m-chloroperoxybenzoic acid (6.5 9) in methylene chloride (120 mi) at 05C. The mixture was left overnight at room temperature and then filtered, washed successively with brine containing sodium sulphite, aqueous sodium carbonate, and brine, dried over magnesium sulphate, and evaporated down. The residue was distilled to give 5.6 g of the desired product, boiling point 85-86 'C at a pressure of 0.9 mm Hg.

Example 8 Preparation of 2-ethyl-5-hydroxy-5-ethyl-hept- 1 one

The process described in Example 6 was repeated replacing the epoxide with

The desired compound was obtained in 88.60ó yield, and had an NMR spectrum as follows: 1.0(10H,multiplet); 1.6(6H,multiplet); 2.0(4H,muitiplet); 4.7(2H,broad singlet).

Elemental Analysis C H Calculated for C11H 0 77 6 13.02 Found 76.4 13.2 Example 9 Preparation of 2, 2-diell yl-5-h ydrnxym e th yl-5-eth yloxolan e The process described in Example 7 was repeated using the product of Example 8 as starting material. The product was obtained in 80.5% yield.

Example 10 Preparation of 2-ethyl-3-methoxyethoxymethoxy-5-hydroxy-5-methylhex- 1 -ene Magnesium (2.36 g) was dissolved in 120 ml diethyl ether containing methyl iodide (6.2 ml) 2-Ethyl-3-methox\ > ethoxyrr,ethoxy-4-ethoxycarbonylbut-1-ene (9.84 g) dissolved in 20 ml diethyl ether was added dropwise over 20 minutes, the rate of addition being such that a gentle reflux was maintained. A heavy oily precipitate separated out. Excess saturated ammonium chloride solution was added, the mixture was extracted with diethyl ether, washed with brine, dried over magnesium sulphate and evaporated down. The crude product was purified on a silica gel column using 5% acetone in petrol as eluant. 7.5 g of the desired product were obtained.

NMR 1.1(3H,triplet); 1.3(6H,doublet); 1 .6-2.2(4H,complex); 3.3(3H,singlet); 3.4(5H,complex); 4.5(1 H,multiplet); 4.6(2H,broad singlet); 4.9(1 H,broad singlet); 5.0(1 H ,broad singlet).

Claims

1. A compound of the general formula

in which each of R' and R2 independently represents a hydrogen atom or an optionallysubstituted alkyl, cycloalkyl or aryl group, or R1 and R2 together represent an alkylene group; each of R3, R4, R5 and RB independently represents a hydrogen atom or an optionally-substituted alkyl, alkoxy or aryl group; R7 represents an optionally-substituted alkyl group; and R3 represents a hydrogen atom or an optionally-substituted alkyl group.

2. A compound as claimed in Claim 1, in which each of R' and R2 independently represents a hydrogen atom, an alkyl group having up to 6 carbon atoms or an optionally-substituted phenyl group, or R1 and R2 together represent an alkylene group having up to 6 carbon atoms.

3. A compound as claimed in Claim 2, in which each of R1 and R2 independently represents a hydrogen atom, a methyl group or an ethyl group, or P1 and R2 together represent a pentamethylene group.

4. A compound as claimed in any one of Claims 1 to 3, in which each of R3. R4, R5 and P6 independently represents a hydrogen atom or an alkyl or alkoxy group having up to 6 carbon atoms optionally substituted by an alkoxy or alkoxyalkoxy group having up to 6 carbon atoms.

5. A compound as claimed in any one of Claims 1 to 4, in which R7 represents a methyl, ethyl, halomethyl or methoxymethyl group.

6. A compound as claimed in any one of Claims 1 to 4, in which R3 represents a hydrogen atom.

7. A compound as claimed in Claim 1 and named in any one of Examples 1, 4, 6, 8 and 10 herein.

8. A process for the preparation of a compound of the general formula

in which R1, R2, R3, Rl, R5. R6, R7 and R8 have the meanings given for the general formula I, which comprises reacting a compound of the general formula I with an electrophilic epoxidising agent.

9. A process as claimed in Claim 8. in which the epoxidising agent is an aliphatic or aromatic peroxyacid.

10. A process as claimed in Claim 9, in which the epoxidising agent is meta-chloroperoxybenzoic acid.

11. A process as claimed in any one of Claims 8 to 1 0, carried out at a temperature in the range of from - 10 to 80'C.

1 2. A process as claimed in any one of Claims 8 to 11. in which the molar ratio of the compound of the general formula I to the epoxidising agent is in the range of from 1:1 to 1:2.

1 3. A process as claimed in any one of Claims 8 to 12, which also comprises a further step in which at least part of the resulting compound of the general formula II is converted into an alkali metal or alkaline earth metal salt thereof. and reacted with a compound of the general formula

in which Hal represents a halogen atom, R9 represents a hydrogen atom or an optionally substituted alkyl group. and Ar represents an optionally substituted phenyl group or an optionally substituted fully unsaturated ring having 5 or 6 carbon atoms in the ring of which one is a nitrogen atom and the remainder are carbon atoms; to give a compound of the general formula

in which R' to P9 and Ar have the meanings given above.

14. A process as claimed in Claim 8, carried out substantially as described in any one of Examples 2. 5. 7 and 9 herein.

1 5. A compound of formula II when prepared by a process according to any one of Claims 8 to 12 and 14.

1 6. A compound of formula IV when prepared by a process according to Claim 13.