DE3101461A1 - Unsaturated alcohols and their use for the preparation of oxolanes - Google Patents

Description

Alcohols and their use in manufacture

The invention relates to new unsaturated alcohols and their use for the preparation of oxolanes.

In DE-OS 27 49 974 and EP application 0000002 are certain Oxolane derivatives indicated which are suitable as herbicides.

Such oxolane derivatives have the general formula

R 'I

(D

Ar-CH-CH

1 Q
in which the groups R to R ^ have different meanings and Ar is one _; optionally substituted phenyl group. GB-PS 79 00613 describes similar oxolanes in which Ar is an optionally substituted, fully unsaturated ring with 5 or 6 ring atoms, one of which is a nitrogen atom and the remaining carbon atoms. In general, the compounds of most interest as herbicides are those of the formula I given above in which R 'is optionally

/ 2

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substituted _; Is an alkyl group. Such compounds can be prepared by reacting an oxolane alcohol of the general formula

HIGH
with a compound of the formula

: λγ-CH- Hai

in which shark is a halogen atom.

However, the oxolane alcohols are relatively difficult to synthesize. A new group of olefinic alcohols has now been found which leads to the desired oxolane alcohols can be converted.

The invention therefore relates to a compound of the general formula

R 'R ^ R ^ R ¹

ο I I I I -

R-CH = C-C-C-C-R * R R OH

(D

1 ?
in which the radicals R and R independently of one another each have a hydrogen atom or an optionally substituted alkyl,

1 ? Cycloalkyl or aryl group or R and R together an alkylene

yy ygpp

group, the radicals R, R, R ^ and R a _/ given substituted independently of one another each represent a hydrogen atom or an, optionally substituted, alkyl, alkoxy or aryl group, R ^, alkyl group and R is a hydrogen atom or a gegebenenfalls- substituted _# alkyl group.

.:. .-. 310H61

: - ο ■■ -

Those optionally substituted in a given group any substituents present can be, for example, one or more substituents which are selected independently of one another from halogen atoms, especially chlorine and fluorine atoms and alkyl, alkox Alkoxyalkoxy, aryl and aryloxy groups. Alkyl, cycloalkyl, aryl, alkylene, alkoxy, alkoxyalkoxy and aryloxy groups preferably have up to eight carbon atoms. The preferred aryl and aryloxy groups are phenyl and phenoxy groups.

1 2
Preferably, R and R, independently of one another, each denote a hydrogen atom, an alkyl group with up to 6 carbon atoms or an ₍ optionally substituted, phenyl group or R and R together an alkylene group with up to 6 carbon atoms)

1 2 atoms. In particular, R and R are each independently of one another a hydrogen atom, a methyl or ethyl group or

1 2
R and R together represent a pentamethylene group.

3 4 5 6
R, R, R and R preferably, independently of one, each denote a hydrogen atom or an alkyl or alkoxy group with up to 6 carbon atoms, which is optionally substituted by an alkoxy or alkoxyalkoxy group with up to 6 carbon atoms. In particular, three of the radicals R, r4, r5 and R6 denote hydrogen atoms and the fourth denotes a hydrogen atom or a methoxy group which is optionally substituted by a methoxyethoxy group.

R preferably denotes an alkyl group with up to 6 carbon atoms which can be unsubstituted or substituted. Into the-

¹ I.

in particular, R denotes methyl, ethyl, halomethyl or Methoxymethyl group.

8th
R is preferably a hydrogen atom.

As indicated above, the compounds of the general formula I can be cyclized with the formation of oxolane alcohols. The invention therefore also relates to a process for the preparation of a compound of the general formula

R ¹

,8th

R HO ^> C1

(II)

R ² ,

7 8
R and R the above at the

in which R ", R", R ^, R ^, R-% R ^v
general formula I have the meaning given by reacting a compound of general formula I with an electrophilic epoxidizing agent.

Suitable electrophilic epoxidizing agents include hydrogen peroxide, alkali peroxides or hypohalites, metal perborates, Peroxyacetyl nitrate and silver oxide. Particularly suitable electrophilic epoxidizing agents are peroxy acids e.g. aliphatic peroxy acids such as peroxyacetic acid or peroxyformic acid or, preferably, aromatic peroxy acids such as unsubstituted or substituted peroxybenzoic acid. Particularly suitable such agents are perbenzoic acids substituted by halogen, e.g., acids in which the phenyl ring is substituted by a or two chlorine and / or bromine atoms is substituted. In particular, m-chloroperbenzoic acid is preferred.

The reaction is conveniently carried out in the presence of an inert solvent e.g. a liquid hydrocarbon, chlorinated hydrocarbons, ethers or esters such as benzene, toluene, methylene chloride, carbon tetrachloride, diethyl ether or ethyl acetate carried out. Mixtures of solvents can also be used.

The reaction is preferably carried out at a temperature in the range of -10 to 8O ⁰ C., particularly at 0 to 20 ⁰ C. In some cases it can be advantageous to carry out 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 more critical

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Meaning. The compounds of general formula I and the electrophilic epoxidizing agent are preferably mixed in approximately equimolar amounts or a slight excess of epoxidizing agent is used. The molar ratio of compounds of the general formula I to electrophilic epoxidizing agent is preferably in the range from 1: 1 to 1: 2, in particular 1: 1 to 1: 1.5. Favorable yield can be obtained, but also A, if desired also with a molar ratio of up to 1:10 or, the resulting compound of the general formula can be extracted from the reaction mixture by any suitable work-up procedure II. _{However, SeIn 1} can advantageously carry out a further chemical reaction with the aid of the compound of the general formula II either after isolation or directly in situ in the reaction mixture. In a preferred embodiment of the y lization process according to the invention, at least part of the resulting compound of the general formula II is converted into an alkali or alkaline earth metal salt and reacted with a compound of the general formula

Ar - CH - Hal (III)

in the Hai a halogen atom, R ^ a hydrogen atom or a,

/is '

optionally substituted ^ alkyl group 'and Ar an optionally substituted ^ henyl group or optionally substituted fully unsaturated heterocyclic group with 5 or 6 ring atoms of which one is a nitrogen atom and the remainder are carbon atoms to form a compound of the general formula _R 5 ^

(IV)

H? E ⁸

₁ qAt-CH-O-CH R

in which R to R ^y and Ar have the meaning given above.

/ 6

Preferably R ^ is a hydrogen atom.

Ar is preferably not substituted or by one or more identical or different substituents from the group consisting of halogen atoms, especially chlorine oda? Fiuciratcma, and substituted alkyl groups with up to 6 carbon atoms, especially methyl or ethyl groups. For example, Ar can represent an ₍ optionally substituted phenyl group _; especially an unsubstituted phenyl group or a 2-methyl, 2-fluoro, 2-chloro or 2,6-dichlorophenyl group.

Under a optionally substituted fully unsaturated heterocyclic group is an optionally SUbStItUIe ^ e ₁ pyridyl, pyrrolyl and Azacyclopentadienylgruppe is to be understood. For example, the group Ar can represent one of the following groups.

N ™ 3 N

When Ar is a heterocyclic group, this is preferred bound to the rest of the molecule through a carbon atom and the nitrogen atom is in the ring preferably adjacent to this carbon atom. For example Ar can mean a 2-pyridyl group ^ the unsubstituted or substituted in the 3- or 6-position by a chlorine or fluorine atom or a methyl or ethyl group is.

The reaction of the salt of the compound of the general formula II with the compound of the general formula III will most conveniently either without isolating the compound of general formula II from the reaction mixture of the cyclization reaction or by reacting the crude product resulting from evaporation of the solvent from the reaction mixture.

■ 310U61

~ Jr -

The oxolane alcohol of the formula II can be converted into a salt by reaction with a base. Alkali hydroxides, alkoxides or hydrides are suitable bases. The alcohol can be converted to the salt prior to mixing with the compound of formula III or the salt can be formed in situ by mixing the compounds of formulas II and III in the presence of a base. Any suitable solvent can be used for the reaction, for example an aromatic hydrocarbon such as benzene or toluene. The reaction can be carried out up to 150 ⁰ C, for example at a temperature in the range of 50th The reaction is conveniently carried out at the reflux temperature of the solution used.

The compounds of the general formula I can be prepared by processes analogous to known processes. The exact procedure used depends of course on the meaning d <
Procedures are:

1 8 the meaning of the substituents R to R from. Three suitable

1. A process that runs particularly satisfactorily,

if at least one of the radicals R ^ and R is a hydrogen

1 2

atom and R and R are not hydrogen atoms or

1 2 ^ 5 h
if all radicals R, R, R- ^ and R are hydrogen atoms and that is generally not so favorable if one of the

R ^ and R is an alkoxy group. . comprises the reaction of an epoxide of the general formula

(V)

with a Grignard reagent of the general formula

ο I I

R-CH = C-C- MgHaI (Vl)

/8th

4A

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in which Hal denotes a chlorine, bromine or iodine atom ₍ under conditions as are usual when a Grignard reagent is used.

2. A method of making compounds in which

1 2 '

at least one of the radicals R and R is not a hydrogen atom comprises the reaction of a compound of the general formula

R ⁷ R ⁵ R ³ ο
₈ III Il

R -CH = C-C-C-C-X (VII)

> J *

ρ in which X has the same meaning as given for R in the general formula I _g or an alkoxy group means ^ with a Grignard reagent of the general formula

R ¹ HgHaI (VIII)

in which Hai means a chlorine, bromine or iodine atom and R has the meaning given in the general formula with the exception of a hydrogen atom. When X is an alkoxy group means, you get a connection of the general

2 1

Formula Ij in which R has the same meaning as R, since the alkoxy group X is split off from the molecule when two groups R are added.

3. To produce compounds of the general formula I, at

1 2
where R and R are both hydrogen atoms, an ester of the formula VII in which X is an alkoxy group, with a selective Redi
hydride are implemented.

with a selective reducing agent, e.g. Lithium aluminum

It may in some cases be particularly advantageous ^ a compound of general formula I produce by first producing a corresponding compound in which _R

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1 8
one of the groups R to R has a different meaning and then to lead this group into the desired group.

The invention is illustrated in more detail by the following examples.

The indicated NMR values are based on tetramethylsilane in CDCl ₅ .

example 1

2-ethyl-4-methoxyethoxymethoxy-5-hydroxy-5-methylhex-1-en

CH ₂ -O- (CH _{2) 2} - 0 - CH ₃

C ₂ H ₅ O CH ₃

CH = C - CH_ - CH - C - CH-.
2, 5

OH

a) 5.9 g of sodium were dissolved in 300 ml of absolute ethanol and 31.72 g of ethyl acetoacetate were added. The mixture was stirred for 15 min, 40 g of 2-bromomethylbut-1-ene within Added 30 min and the mixture heated under reflux for 2 h. The mixture was then poured into salt water extracted a few times with diethyl ether, washed with salt water, dried and evaporated. When distilling 29 g of the residue under vacuum were obtained accordingly a 6O-5X> igen yield of 2-ethyl-4-methylcarbonyl-4-ethoxycarbonylbut-1-en, Bp 120-127 ° C at 13.3 mbar.

b) 25 g of the product according to a) were added to 6.2 g of a 50% strength solution of sodium hydride in oil, dissolved in 250 ml of benzene, and the mixture was stirred for 2 h. Then 20.4 g of dibenzoyl peroxide (CgHcCO ₂ )? ^{added in} 200 ml of benzene within 30 min. The mixture was stirred for a further 2 hours and then poured into water and a few times with diethyl ether

310H61 - 1 # -

extracted, dried and distilled under vacuum. 24 g were obtained ₍ corresponding to a yield in stage b) of 89.5 %, 2 ^ 1 ^ 1-4-1116 ^ 103 ^ 0 ^ 1-4 ^^ 0 ^ 08 ^ 0 ^ 1-4-benzoyloxybut-1 -en, bp 160 ° C at 1.33 mbar

c) 250 mg of sodium were dissolved in 250 ml of dry ethanol and 22.65 g of the product according to b) were added. The mixture was stirred overnight and then refluxed for 2 hours. 0.5 g of ammonium chloride and 0.25 ml of water were added and the mixture was stirred for a further 0.5 h. The mixture was then filtered and the solvent evaporated. The residue was dissolved in diethyl ether, the mixture was filtered and the ether was evaporated. 2-Ethyl-4-hydroxy-4-ethoxycarbonylbut-1-ene, which was identified by the NMR spectrum, was obtained. This residue was dissolved in 200 ml of methylene chloride containing 12.5 ml of methoxyethoxymethyl chloride and 22.5 ml of ethyldiisopropylamine and the mixture was stirred overnight. A further 5 ml of methoxyethoxymethyl chloride and 10 ml of ethyldiisopropylanine were added. The mixture was refluxed for 3 hours, then poured into water with 30% hydrochloric acid and then washed with brine, dried over potassium carbonate and evaporated. The residue was eluted through a silica gel column with the aid of methylene chloride. The solvent was evaporated and the product distilled. This gave 14.5 g of 2-ethyl-4-methoxyäthoxymethoxy-4-ethoxycarbonyl-but-1-ene, b.p. 158-162 ⁰ C at 16.0 mbar.

d) 3.3 g of magnesium were dissolved in a solution of 19.1 g of methyl iodide in diethyl ether and an ethereal solution of 14 g of the ester obtained under c) was added to the refluxing solution over the course of 20 minutes. The mixture was then stirred for an additional 2 hours. Then saturated ammonium chloride solution was added, the mixture was extracted with diethyl ether with acid solution, dried over magnesium sulfate and evaporated. The residue was distilled. To give 9.5 of the title compound, bp 115-120 g ⁰ C at 2.7 mbar. NMR spectrum: 0.9 (3H, triplet); 1.2 (6H,

'It

Singlet); 1.8-2.3 (4H, complex); 3.2 (IH, broad); 3.3 (3H, singlet); 3.5 (5H, complex); 4.7 (4H, complex),

Example 2

2.2-Dlmethyl-5 ~ methoxyethoxymethoxy ~ 5-hydroxy-methyl-5 » ethyloxolan

9.5 g of the corresponding; The olefinic alcohol prepared in Example 1 was dissolved in methyl chloride and added to 8.65 g of m-chloroperbenzoic acid (85 96 pure) in methylene chloride at ⁰ ° C. within 30 minutes. The mixture was stirred for 20 hours and then washed successively with an aqueous solution of sodium sulfite, sodium bicarbonate and sodium chloride and dried. The solvent was evaporated leaving a crude product ₍ which was identified as a mixture of the isomers of the desired product. NMR: 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 further as indicated in Example 3 without further purification.

Example 3

2.2-Dimethyl-3-methoxyethox: ymethoxy-5-benzyloxy-methyl-5-ethyloxolane

All of the crude product obtained in Example 2 was dissolved in 80 ml of toluene and made into a solution of 2.15 with stirring Sodium hydride (50% suspension in oil) in 150 ml of dry Toluene added within 15 minutes.

The mixture was refluxed for 40 minutes and 8.25 g of benzyl bromide in 50 ml of toluene were then added dropwise. It was refluxed and stirred for a further 18 h. The mixture was then poured into brine with diethyl ether

/ 12

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extracted and dried over magnesite sulfate. The solvent has been removed. 17.5 g of raw material were obtained which passed through a silica gel column with the aid of acetone / petroleum ether was chromatographed as the eluent. 8.2 g of des were obtained desired pure product. The NMR spectrum showed that a mixture of the geometric isomers was present.

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, broad triplet); 4.5 (2H, singlet); 4.7 (2H, singlet); 7.2 (5H, singlet)

Elemental analysis

C H

for ^C 20 ^H 32 ° 5 68.15 9.5 found 67.5 9.7

Example 4 2-methyl-4-methoxygthoxvmethoxv-5-hvdroxv-5-methoxyhex-1-en

The title compound was prepared analogously to the procedure described in Example 1 using 2-bromomethylpropene as starting material. / ■■

NMR; , '

1.1 (6H, singlet); 1.7 (3H, breWBS 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-ben2vIo _< icyTsethyl-5-methyl-oxolane

The title compound was obtained in an analogous manner to Procedure 2 Method prepared using the compound of Example 4 as a starting material. The NMR spectrum showed that the product was a mixture of the geometric isomers.

"V .: 310U61

1.2 (9H, singlet); 1.5-2.5 (2H, complex); 2.3 (3H, singlet); 3.4 (6H, complex); 3.9 (1H, broad triplet); £ 4 (2H, singlet); 4.6 (2H, broad singlet); 7.2 (5H, singlet).

Elemental analysis

C H

for ^C 19 ^H 3O ° 5 67.4 8.94

found . 67.4 9.3

Example 6 2-ethyl-5-hydroxy-5-spirocyclohexyl-pent-1-en

C ₅ H ₁ . QH

CH, = C - CH "- CH ₀ - C 2 2 2

3.21 g of magnesium was added to 75 ml of diethyl ether and cooled to ⁰ ° C. Under a nitrogen atmosphere, 13.3 g of 2-bromomethylbut-1-ene in 50 ml of diethyl ether were added over the course of 3 hours. The cooling bath was removed and stirring was continued for an additional hour. Then 5 g of methylenecyclohexane oxide in 25 ml of diethyl ether were added over the course of 20 minutes and the mixture was stirred for a further 30 minutes. The mixture was then poured into aqueous ammonium chloride solution ^ the organic phase separated ^ washed with salt water, dried over sodium sulfate and evaporated. The residue was distilled under reduced pressure. 11.18 g of a crude product were obtained ₍ which was chromatographed by chromatography using 2 % acetone in petroleum ether as the eluent. 7.85 g of the desired product were obtained, corresponding to an 81% yield. NMR: 1.0 ( 3H, triplet); 1.5 (12H, broad singlet); 2.0 (5H, complex); 4.6 (2H, broad singlet).

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Example 7 2-splrocyclohexyl-5-hydroxymethyl-5-ethyloxolane

5.5 g of the olefinic alcohol prepared according to Example 6 were dissolved in 20 ml of methylene chloride and ^{added dropwise to 6.5 g of m-chloroperbenzoic acid in 120 ml of methylene chloride at 0} ° C. The mixture was left to stand overnight at room temperature, then filtered and successively with Saline solution.

'Sodium /

containing sodium sulfite, aqueous ⁷ carbonate solution and brine, washed over magnesium sulfate and evaporated. The residue was distilled. This gave 5.6 g of the desired product, bp 85 -86 ⁰ C at 1.2 mbar.

Example 8

2-ethyl-5-hydroxy-5-ethyl-hept-1-en

CH ₁ . QH

r ⁵ ι

CH ₂ = C - CH ₂ - CH ₂ - C - C ₂ H ₅

C ₂ H ₅

The procedure described in Example 6 was repeated, using as epoxy

(C ₂ H ₅ )., C CH ₂

was used.

The desired compound was in 88.6 # yield and had the following NMR spectrum: 1.0 (10H, multiplet); 1.6 (6H, multiplet); 2.0 (4H, multiplet); 4.7 (2H, broad singlet);

Elemental Analysis '

for C ₁₁ H ₂₂ O C. 6th H calculated 77 4th 13.02 found 76 13.2

Example 9

2.2-Diethyl-5-hydroxymethyl-5-ethyloxolane .

The procedure of Example 7 was repeated with the The product of Example 8 was used as a starting material. The product was obtained in 80.5% yield.

Example 10 2-A ^; hyl-3-methoxy-methoxymethoxy-5-hydroxy-5-methylhex-1-ene

2.36 g of magnesium were dissolved in 120 ml of diethyl ether containing 6.2 ml of methyl iodide. Then 9.84 g of 2-ethyl-3-methoxyethoxymethoxy-4-ethoxycarbonylbut-i-ene in 20 ml of diethyl ether were added dropwise over a period of 20 minutes, the rate of addition being set so that a gentle reflux was maintained. It differed An excess of saturated ammonium chloride solution was added, the mixture extracted with diethyl ether, dried over magnesium sulfate and evaporated with salt solution. The crude product was purified over a silica oil column using 5 % acetone in petroleum ether as the eluent. 7.5 g of the desired product were obtained.

1.1 (3H, triplet); 1.3 (6H, doublet); 1.6-2.2 (4H, complex); 3.3 (3H, singlet); 3.4 (5H, complex); 4.5 (1H, multiplet); 4.6 (2H, broad singlet); 4.9 (1H, broad singlet); 5.0 (1H, broad singlet).

Claims (12)

Claims 1. J Unsaturated alcohols of the general formula R ' H- R-CH = C-C-C-C-R B H OH (I) in which R and R are each a hydrogen independently of one another atom or an optionally substituted alkyl, 12th Cycloalkyl or aryl group or R and R together an alkylene group, R, R, R ⁵ and R independently of one another in each case a hydrogen atom or an ₍ optionally substituted. Alkyl, alkoxy or aryl group, R ⁷ an optionally substituted alkyl group and R) Hydrogen atom or _{f denotes} an optionally substituted alkyl group. 2. A compound according to claim 1, characterized in that 1 2
net that R and R, independently of one another, each represent a hydrogen atom, an alkyl group with up to 6 carbon atoms or an optionally substituted phenyl group or R and R together represent an alkylene group of up to 6 carbon atoms mean. • ■. : - 2 - 3. A compound according to claim 1 or 2, characterized in that g e k e η η - 1 2 draws that R and R are independent of each other, respectively a hydrogen atom, a methyl or ethyl group or 1 2
R and R together represent a pentamethylene group. 4. A compound according to claim 1 to 3, characterized in that R, R, R ^ and R are independent of one another In each case a hydrogen atom or an alkyl or alkoxy group with up to 6 carbon atoms mean, which optionally is substituted by an alkoxy or alkoxyalkoxy group of up to 6 carbon atoms. 5. A compound according to claim 1 to 4, characterized in that g e k e η η - 7th
indicates that R 'denotes a methyl, ethyl, halomethyl or methoxymethyl group. 6. A compound according to claim 1 to 4, characterized in that g e k e η η - indicates that R is a hydrogen atom. 7. Use of the compounds according to claim 1 to 6 for the preparation a compound of the general formula H ⁶ -l ~ r5 (II) HO - CH " _R l in the R, R, R, R, R, R, R 'and R those in the general Formula I have given meaning by reaction with an electrophilic epoxidizing agent. 8. Use according to claim 7, characterized in that that an aliphatic or aromatic peracid is used as the epoxidizing agent. 9. Use according to claim 8, characterized in that that the epoxidizing agent used is m-chloroperbenzoic acid used. / 3 10. Use according to claim 7 to 9, characterized in that one works at a temperature in the range of -10 to 80 ^0C. 11. Use according to claim 1 to 10, characterized draws that a molar ratio of compound of the general formula I ζυ epoxidizing agent in the range from 1: 1 to 1: 2 applies. 12. Use according to claim 7 to 11, characterized in that at least part of the resulting compound of the general formula II is converted into an alkali or alkaline earth metal salt and with a compound of the general formula _n Ar-CH- Hai (III) in which Hal is a halogen atom, R ^ is a hydrogen atom or a, optionally substituted alkyl group and Ar is, optionally substituted phenyl group or one, optionally / unsaturated completely substituted ⁷ ring with z> or 6 carbon atoms in the ring of which one is a nitrogen atom and the remainder is carbon atoms, means forming a compound of the general formula R- R ⁹ R ^{8 R} 1 "" * 0 R. - CH \
- 0 - R ⁷ ^ R. CH ^ 1 Ar _S 3- 1 Q
where R to R and Ar have the meanings given above.