CH636332A5 - Process for preparing monoalkylated dihydroxybenzenes - Google Patents

Description

The invention relates to a chemical process and in particular to a process for the monoalkylation of dihydroxybenzenes.

The monoalkylation of dihydroxybenzenes, e.g. Hydroquinone is difficult because both hydroxyl groups tend to react with the alkylating agent. Newman and Colla [Journal of Organic Chemistry, Vol. 39, pp. 214 and 215 (1974)] state that the monoalkylation of hydroquinone is a problem for which no generally satisfactory solution has yet been developed. Monoalkylation was accomplished using a large excess of hydroquinone, but this method is not effective when the yield is calculated on hydroquinone. In general, the alkylation of hydroquinone results from that

HO - "^

8th

(I)

Ö - A - Z

wherein A represents an optionally substituted straight-chain or branched-chain alkylene radical, in which the chain can be interrupted by oxygen or sulfur atoms, or an aralkylene or alkenylene radical, Z stands for an electron-withdrawing group and B stands for a hydrogen or halogen atom or an alkyl or alkoxy radical which is carried out by

55

(II)

wherein B has the meaning given above, with an alkylating agent of the formula:

60

W-A-Z

m in which W represents a halogen atom and A and Z have the meanings given above, in an alcoholic solvent and in the presence of approximately 2 equivalents of a base.

Examples of groups A are methylene and ethylene. Examples of electron-withdrawing groups Z are -COOR, -CN and -CONRR ', where R and R' are each un-

3rd

636332

independently of one another represent a hydrogen atom or an optionally substituted hydrocarbon radical or R and R 'together form a heterocyclic ring which includes the amide nitrogen atom. When R and R 'are hydrocarbon radicals, it is preferred that they are alkyl radicals, especially lower alkyl radicals.

Specific examples of groups Z are methoxycarbonyl, ethoxycarbonyl and aminocarbonyl.

If B represents an alkyl or alkoxy radical, then it is preferred that they are lower alkyl or lower alkoxy radicals. However, B is preferably a hydrogen atom.

Examples of alkyl and alkoxy radicals B are methyl, ethyl, methoxy and ethoxy.

Examples of halogen atoms B and W are chlorine and bromine.

Examples of alcoholic solvents that can be used in the process are ethanol and methanol.

An example of a base that can be used is sodium methoxide.

Examples of the dihydroxybenzene starting materials of formula (II) that can be used are hydroquinone, chlorohydroquinone and resorcinol.

Examples of alkylating agents of the formula (III) which can be used are methyl chloroacetate, ethyl chloroacetate and methyl a-chloropropionate.

The terms “lower alkyl” and “lower alkoxy” in this description refer to alkyl or alkoxy radicals having 1 to 4 carbon atoms.

The reaction can be carried out at normal room temperature or at elevated temperatures, for a reaction time of, for example, 4 to 24 hours, which depends on the temperature. The reaction product of formula (I) can be isolated by conventional methods, for example by distillation or by evaporating part of the solvent and allowing the rest of the reaction mixture to cool, so that the product crystallizes out. Another possibility is to pour the entire reaction mixture into water, to separate the precipitated product and, if necessary, to purify it by crystallization or distillation.

The process gives good yields, i.e. up to 80% or even more of monoalkylation products of hydroquinone and other dihydroxybenzenes and derivatives, even when using alkylating agents which are sensitive to alkali, e.g. Esters of chloroacetic acid, with virtually no hydrolysis of these agents.

The monoalkylated dihydroxybenzenes obtained according to the present invention are of value as intermediates in the synthesis of dyes. They enable the production of certain such dyes in cheaper and more expedient ways than the known ways.

For example, anthraquinone dyes of the type:

KH,

0 OH

(IV)

in which R represents an alkyl group, can be prepared by reacting 1 mol of 1-amino-2-bromo-4-hydroxyanthraquinone with 3 mol of, for example, hydroquinone to give an intermediate of the formula:

NH

together with some of the bis compound (VI) in which 2 moles of the anthraquinone starting material reacted with 1 mole of hydroquinone. The use of 3 moles of hydroquinone per mole of 1 amino-2-bromo-4-hydroxyanthraquinone is necessary to achieve a reasonable yield of the monocondensation product (V). The compound (V) is then reacted, for example, with chloroacetic acid ethyl ester or bromoacetic acid ethyl ester, the desired dye of the formula (IV) being obtained.

The above method has numerous disadvantages, namely:

(a) 2 moles of the original 3 moles of hydroquinone are not used in the reaction and must be discarded or recovered;

(b) the insoluble bis-compound (VI) formed as a by-product is useless and must be discarded, which is a waste of expensive raw material;

(c) an expensive purification step is necessary to obtain the desired intermediate (v) free of unreacted starting materials and by-products; and

(d) some alkylation of intermediate (V) by chloro- or bromoacetic acid esters takes place on the hydroxyl group in the 4-position of the anthraquinone nucleus, which is a further waste.

These disadvantages are eliminated by the method according to the invention, which enables a compound of the formula:

where R stands for an alkyl group, in a good yield from hydroquinone and a chloro- or bromoacetic acid ester. The compound (VII) can then be easily reacted with l-amino-2-bromo-4-hydroxyanthraquinone to give a dye of the formula (IV) without the difficulty of the above process.

The use of an intermediate product, which can be obtained by the process according to the invention, in the production of an anthraquinone dye is described below:

3.6 parts (4-hydroxyphenoxy) methyl acetate, 1.4 parts of anhydrous potassium carbonate and 5 parts of dimethylformamide are heated to 100 ° C. for 30 minutes with stirring. 3.2 parts of 1-amino-2-bromo-4-hydroxyanthraquinone are then added, followed by the addition of a further 3 parts of dimethylformamide. The reaction mixture is then heated to 110 ° C. for 1.5 hours. The mixture is cooled and diluted with 100 parts of methanol, 2 parts of 1-amino-2- (4'-methoxycarbonylmethoxy) phenoxy-4-hydroxyanthraquinone precipitate out, which is separated off by filtration as a red solid, mp 205 ° C.

The invention is illustrated by the following examples, in which the parts are expressed in weight.

example 1

13.8 parts of sodium are added to 300 parts of methanol under nitrogen, and the resulting solution becomes

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

636 332

4th

cooled to 28 ° C. 33 parts of hydroquinone are added, resulting in a yellow solution. Finally, 36 parts of methyl chloroacetate are added all at once to the reaction mixture, which is stirred for a further 17 hours at room temperature. 20 parts of glacial acetic acid are then added, the salts are removed by filtration and the filtrates are evaporated to dryness to give an oil. Addition of 400 parts of water to the oil induces crystallization. The solid thus formed is separated off by filtration, washed with water and dried, 35 parts of (4-hydroxyphenoxy) methyl acetate, mp 106 ° C., being obtained.

Example 2

9.2 parts of sodium are added to 210 parts of dry ethanol under nitrogen and the resulting solution is cooled to 25 ° C. 22 parts of hydroquinone are added, resulting in a yellow solution. Finally, 24.5 parts of ethyl chloroacetate are added all at once, and the reaction mixture is stirred under reflux for a further 18 hours. 20 parts of glacial acetic acid are added, the salts are removed by filtration and the filtrates are evaporated to dryness. 300 parts of water are added to the solid and the product is isolated by filtration. 22.8 parts of 4-Hydroxyphen-oxy-acetic acid ethyl ester, mp 126 ° C., are obtained.

Example 3

4.6 parts of sodium are added to 110 parts of pure methanol under nitrogen and the resulting solution is cooled to 25 ° C. 11 parts of hydroquinone are added, giving a yellow solution, and finally 13.7 parts of ethyl a-chloropropionate are added. The reaction mixture is then heated to reflux for 20 hours. 15 parts of glacial acetic acid are added, the salts are removed by filtration and the filtrates are distilled off, giving 21 parts of methyl 2- (4-hydroxyphenoxy) propionate, bp 126 ° C./0.25 mm.

Example 4

To 6.9 parts of sodium, which are dissolved in 120 parts of methanol, 11 parts of hydroquinone and 9.5 parts of ghloroacetic acid are added under nitrogen. The resulting suspension is heated to reflux for 4 hours, 10 parts of glacial acetic acid are added, and the solvent is removed by distillation to give 4-hydroxyphenoxyacetic acid as an impure gum.

150 parts of methanol and 5 parts of concentrated sulfuric acid are added, producing a white precipitate. The undesired salts are filtered off, a further 5 parts of concentrated sulfuric acid are added, and the solution is heated moderately overnight. Pouring the mixture into 200 parts of ice gives 6 parts of 4-hydroxyphenoxyacetic acid methyl ester, mp 106 ° C.

Examples 5 to 10 25 The following table relates to further examples according to the invention in which the dihydroxybenzene identified in the second column is reacted with the alkylating agent indicated in the third column under the conditions described in the preceding examples. The reaction solvent is shown in the fourth column. The main product of the reaction is given in the fifth column.

Example dihydroxybenzene

Alkylating agent

Main solvent product

5 hydroquinone

6 hydroquinone

7 hydroquinone

8th

9 10

Resorcinol

Resorcinol

Chloro-hydroquinone

Chloroacetamide methanol

N, N-diethyl - «- chloro methanol propionamide a-chlorophenylacetic acid-methanolic acid methyl ester

Chloroacetic acid methyl methanol ester

Bromoacetic acid-methanol

ethyl ester

Chloroacetic acid-methanol methyl ester

4-hydroxyphenoxyacet amide

N, N-diethyl-a-

(4-hydroxyphenoxy) -

propionamide

4-hydroxyphenoxyphe

nylacetic acid methyl

ester

3-hydroxyphenoxyacetic

acid methyl ester

3-hydroxyphenoxyacetic

acid ethyl ester

3-chloro-4-hydroxy

phenoxyacetic acid

methyl ester

Claims (8)

636332 2nd PATENT CLAIMS 1. Process for the preparation of monoalkylated dihydroxybenzenes of the formula: \ = ^ 0-A-Z (I> wherein A represents an optionally substituted unbranched or branched alkylene radical, the chain of which may be interrupted by oxygen or sulfur atoms, or an aralkylene or an alkenylene radical, Z represents an electron-attracting group and B represents hydrogen, a halogen atom or an alkyl or alkoxy radical, thereby characterized that you have a compound of the formula: _ > - / V H0- \ == ^ n OH (II) in an alcoholic solvent and in the presence of approximately two equivalents of a base with an alkylating agent of the formula: W-A-Z (III) wherein W represents a halogen atom. 2. The method according to claim 1, characterized in that Z represents -COOR, -CN or-CONRR1, where R and R1, which are the same or different, each represent hydrogen or an optionally substituted hydrocarbon radical or R and R1 together with the amide nitrogen atom form a heterocyclic ring. 3. The method according to claim 2, characterized in that the hydrocarbon radicals R and R1 are alkyl radicals. 4. The method according to claim 3, characterized in that the alkyl radicals R and R1 are lower alkyl radicals. 5. The method according to any one of claims 1 to 4, characterized in that the alkyl and alkoxy groups B are lower alkyl or lower alkoxy groups. 6. The method according to any one of claims 1 to 4, characterized in that B is hydrogen. 7. Monoalkylated dihydroxybenzenes, prepared by the process according to claim 1. 8. Monoalkylated dihydroxybenzenes according to claim 7, produced by the process according to one of claims 2 to 6. Monosodium salt and poor yields of monoalkylated product using 1 equivalent of the alkylating agent. Alternatively, it is possible to prepare a single-protected hydroquinone, which is itself a difficult process to alkylate and remove the protecting group. The above authors have found that aqueous dioxane gives good yields of monoalkylated product when using alkaline stable alkylating agents such as e.g. tert-butyl bromoacetate, the io tert-butyl group is not hydrolyzed by alkali. Similarly, N-methylpyrrolidone / water gave good yields of monoalkylated product when tert-butyl bromoacetate was used. However, if alkali sensitive groups are present, such as in a-i5 bromoisobutyric acid ethyl ester, then these solvent systems are not useful. Only moderate yields of monoalkylated product are obtained with this alkylating agent if dimethylformamide or dimethyl sulfoxide are used as the solvent. 20 A Review by Moser [Journal of the American Chemical Society, Vol. 72, pp. 1413-1415 (1950)] found that the reaction of the disodium salt of hydroquinone with 1 equivalent of ethyl chloroacetate yielded a 23% yield of monoalkylation product ( with hydrolysis also taking place). Using the monosodium salt of hydroquinone and 1 equivalent of ethyl chloroacetate, approximately 30% monoalkylation (7% acid; 23% ethyl ester) was obtained. The yields of these processes are far too low to be economically attractive. Although the above work relates to hydroquinone, similar difficulties are encountered to a greater or lesser extent with other dihydroxybenzenes and their ring-substituted derivatives. 35 The invention now relates to a process for the preparation of monoalkylated dihydroxybenzenes of the formula: 40