DE1543880C3 - Process for the production of benzo- or naphtho-dioxoles or -oxathiols - Google Patents

Description

in which X is an oxygen or sulfur atom and where the benzene ring is replaced by an or a plurality of alkyl groups or halogen atoms or one formyl group can be substituted or may be condensed with another benzene ring to form a naphthalene ring, by condensation a compound of the general formula

15th

XH

OH

(H)

lysator, copper bronze was used (J. Org. Chem., 16, 1736 [1951]). At atmospheric pressure and with benzyl alcohol or ethylene glycol as solvents lower yields were obtained, which was also heated over a longer period of time. (J. App. Chem., 32, 878 [1959], and 34, 2338 [1961]).

It has now been found that the rate of reaction in the production of benzo or Naphtho-dioxoles or -oxothiols can be increased considerably if the reaction takes place in a highly polar, aprotic solvent is carried out.

In GB-PS 9 56 624 it is stated that tetramethylene sulfone is used as a solvent for special purposes can be used in which a high dielectric constant and a low autoprotolysis constant are desired, but this gave no indication of the process according to the invention refer to.

The inventive method for the preparation of heterocyclic compounds of the general formula

'X \

CH ₂ (I)

the X is an oxygen or sulfur atom and the benzene ring is substituted as above or may be condensed with a methylene dihalide at an elevated temperature under alkaline Conditions in the presence of an organic solvent, characterized in that that a highly polar aprotic solvent is used as the organic solvent.

25 in which X denotes an oxygen or sulfur atom and where the benzene ring can be substituted by one or more alkyl groups or halogen atoms or a formyl group or can be condensed with another benzene ring to form a naphthalene ring, by condensation of a compound of the general formula

XH

35

(H)

OH

The invention relates to a process for the production of benzo- or naphtho-dioxoles or -oxathiols of the general formula

(D

in which X denotes an oxygen or sulfur atom and where the benzene ring is replaced by one or more Alkyl groups or halogen atoms or one formyl group may be substituted or with another Benzene ring can be condensed into a naphthalene ring. Such ring systems are z. B. methylenedioxybenzene, 1,3-benzoxathiol and its derivatives.

It is known that derivatives of methylenedioxybenzene, e.g. B. safrole, piperonal, piperonyl butoxide («- [2-2 - η - butoxyethoxy) - ethoxy] - 4,5 - methylenedioxy-2-propyltoluene) and sesoxane (2- (3,4-methylenedioxyphenoxy) -3,6,9-trioxaundecane), from safrole-containing ethereal substances oils can be produced, in particular from camphor oils. According to a different procedure Methylenedioxybenzene and its derivatives are produced by using a catechol Methylene halide and aqueous alcoholic alkali heated together. ("Organic Synthesis", Vol. I. P. 660 [1964]). This reaction proceeds slowly, in particular with methylene chloride, so that it is expedient must be heated under pressure for a long time. As Katain the X means an oxygen or sulfur atom and the benzene ring may be substituted or fused as above with a methylene dihalide elevated temperature under alkaline conditions in the presence of an organic solvent characterized in that the organic solvent used is a highly polar aprotic solvent used.

Although the increased reaction rate in the highly polar aprotic solvent the Enables the reaction to be carried out in a minimum of time, the ion concentration should ensure an optimal yield the grouping

(obtained by reacting the compound of formula II with alkali) in the solvent not be more than 1 m. The concentration of these ions is thereby preferably as low as possible held that the catechol or hydroxybenzenethiol is slowly added to the reaction mixture. During With this slow addition, the ions react immediately after their formation and are therefore always lying in a very strong dilution. Will the door the reaction required alkaline conditions

prepared by adding an alkali metal hydroxide to the reaction mixture, it is recommended usually, the connection

XH

OH

and the alkali hydroxide separately, simultaneously and slowly, a solution of the methylene dihalide in to add the highly polar aprotic solvent.

Many common organic solvents are somewhat polar, depending on the symmetry in their molecules. An essential feature of the process according to the invention, however, is that the solvent is "highly polar", which is to be understood as meaning a solvent with a dielectric constant of at least 25, at 25 ^° C. At the same time, the solvent to be used must be "aprotic," meaning that it does not contain any hydrogen atoms that can form hydrogen bonds with anions. Alcohols and glycols are therefore not such a solvent, as the hydrogen atom of the hydroxyl group (s) can form hydrogen bonds with anions.

Suitable highly polar aprotic solvents are dimethylformamide, dimethylacetamide and dimethyl sulfoxide and sulfolane, with dimethyl sulfoxide or a derivative thereof being preferred. Suitable Methylene dihalides are, for example, methylene dichloride, methylene dibromide and methylene chlorobromide. Methylene dichloride is preferred.

Suitable starting materials of the formula II are, for example, catechol or o-hydroxybenzenethiol, which are optionally substituted by alkyl groups or the formyl group or halogen atoms can, or o-dihydroxy or o-mercaptohydroxynaphthalene.

Alkaline conditions are required for the process, since the compound of the formula II, but the anionic grouping of the formula derived therefrom

reacts with the methylene dihalide. These alkaline Conditions can be established, for example, by adding an alkali hydroxide to the reaction mixture. Used as a solvent, dimethyl sulfoxide or sulfolane is used, alkali hydroxides are suitable substances for these anions to form in situ. However, if the solvent is dimethylformamide or dimethylacetamide, this leads to water released in the formation of the anion sometimes leads to undesirable hydrolysis of the Solvent. In this case it is therefore often advisable to use a pre-formed dialkali metal derivative of To use compound of formula II or a base such as sodium hydride, so that no water is generated in the formation of the anion. The products of the process are suitable for use in agriculture and veterinary.

They are also valuable starting materials for production of organic compounds in the food, cosmetic and pharmaceutical sectors Preparations and in the agricultural and veterinary fields.

The following examples explain the process according to the invention. The information in parts by weight and Volume parts are in the ratio of kilograms to liters.

B is ρ ie 1 1
Methylenedioxybenzene

a) 11 parts by weight of catechol and 10 parts by weight of methylene chloride were dissolved in 40 parts by volume of dimethyl sulfoxide. Then, 8.3 parts by weight of powdery sodium hydroxide were added, and the reaction mixture was heated at reflux under nitrogen in a bath at 120 ⁰ C. The reaction was brisk. After 10 minutes, steam was passed into the reaction mixture and this was subjected to steam distillation. The distillate obtained was saturated with sodium chloride and extracted with petroleum ether (boiling point 40 to 60 ⁰ C). The petroleum ether extract was washed with aqueous sodium hydroxide and then distilled. 5.6 parts by weight of methylenedioxybenzene (46% yield) with a _{boiling point of 76O} 173 ° to 175 ° C. in the form of a colorless UI which had a refractive index of n's = 1.5377 were obtained.

b) The reaction was carried out as described under (a), except that 100 parts by volume of dimethyl sulfoxide were used. The heating time was 30 minutes. After the work-up described under a) 8.35 parts by weight of methylenedioxybenzene were obtained in 68% yield.

c) The reaction was carried out as described under a), but 150 parts by volume of dimethyl sulfoxide were used. The heating time was 70 minutes. The yield of methylenedioxybenzene was 8.9 parts by weight (73% of theory).

d) The reaction was carried out as described under a), with dimethyl sulfoxide in place of 40 parts by volume of sulfolane were used. The heating time was 3½ hours. The reaction mixture was then worked up as described under a). The yield of methylenedioxybenzene was 4.1 parts by weight (34% of theory).

e) To 11 parts by weight of catechol in 50 parts by volume of methanol were added 4.6 parts by weight of sodium, then the methanol was distilled off at low pressure at 100 ° C and then a solution of 9 parts by weight of methylene chloride in 50 parts by volume of dry to the dry residue of disodium catechol kept under nitrogen Dimethylformamide added. The mixture was stirred under reflux for 1 hour. Steam was then passed in and the product was steam distilled. The distillate thus obtained was saturated with sodium chloride and extracted with petroleum ether (b.p. 40 to 6O ⁰ C). The extract was washed with aqueous sodium hydroxide and then distilled. This gave 6.55 parts by weight of methylenedioxybenzene. The yield was 54% of theory.

f) 500 parts by volume of dimethyl sulfoxide and 100 parts by volume Methylene chloride were under nitrogen in a

Separated at which solids and could enforce the same time, heated apparatus 125 to 130 ⁰ C. Then 110 parts by weight became catechol cookies

in amounts of 5.5 parts by weight each and 83 parts by weight of sodium hydroxide pellets were added in amounts of 4.15 parts by weight each at 5 minute intervals, the total addition time being 105 minutes. The reaction mixture was stirred thoroughly and the internal temperature was kept at 125 to 130.degree. 20 minutes after completion of the addition of catechol and sodium hydroxide were further 20 parts by weight of methyl chloride and 3 parts by weight of sodium hydroxide at a temperature of 125 to 13O ⁰ C the reaction mixture was added, and the whole was stirred at this temperature for a further 70 minutes. The addition attachment for the solids was then replaced by a Vigreux column on which a distillation head was located and with which constant amounts of distillate could be drawn off. There were then added 50 volume parts water and, at 98 to 100 ⁰ C, an azeotropic mixture of methylenedioxybenzene and water distilled off to obtain more water was added in the course of distillation to the reaction mixture slowly. After about 600 parts by volume of distillate had been collected, the methylenedioxybenzene no longer separated from the distillate. Distillation of the residue then gave 490 parts by volume of dimethyl sulfoxide.

The methylenedioxybenzene layer was separated off and the aqueous layer was extracted three times with 50 parts by volume of ether each time. The ether extracts combined with the methylenedioxybenzene layer were dried and then distilled. The yield of methylenedioxybenzene with a _{boiling point of 76O} 173 to 175 ° C. was 91% of theory.

Example 2

4-methyl- (1,2) -methylenedioxybenzene

The reaction was carried out as in Example 1 c), except that 12.4 parts by weight of 4-methylcatechol were used and the heating time was 2 hours. Here, there was obtained 9.5 parts by weight of 4-methyl (l, 2), bp -methylendioxybenzol _753i5 196-197 ⁰ C and a refractive index of n = 1.5308% °. The yield was 70% of theory.

Example 3
3-isopropyl (1,2) methylenedioxybenzene

The reaction was carried out as in Example 1 c), but 15.2 parts by weight of 3-isopropylcatechol were used and the heating time was 2 hours. Here, (, l 2) to obtain 30.1 parts by weight of 3-isopropyl -methylendioxybenzol from Kp. _W 98 ⁰ C and a refractive index of nf = 1.5181. The yield was 80% of theory.

Example. 4th

3-methyl- (1,2) -methylenedioxy-, 5- (1,1,3,3-tetramethylbutyl) benzene

H ₃ CC-CH ₂ -CX

CH,

divide methylene chloride in 75 parts by volume of dimethyl sulfoxide was mixed with 4.2 parts by weight of powdered sodium hydroxide. The mixture was refluxed at 120 ° C under nitrogen for 2 hours. The mixture was then cooled, a little water was added and the oil which separated out was extracted three times with 50 parts by volume of petroleum ether each time. The extract was washed twice with dilute sodium hydroxide solution and then distilled. This gave 9.2 parts by weight of 3-methyl- (1,2) -methylenedioxy - 5 - (1,1,3,3 - tetramethylbutyl) benzene with a boiling point of ₁₄ 162 ⁰ C and a refractive index of η ξ? = 1.5139 in the form of a colorless, slightly sticky oil. The yield was 74% of theory.

"5

Example 5

4-formyl- (1,2) -methylenedioxybenzene (piperonal)

13.8 parts by weight of protocatechus aldehyde in 20 equal parts and 8.3 parts by weight of sodium hydroxide, also in 20 equal parts, were added at a rate of one portion per 5 minutes to a mixture of 50 parts by volume of dimethyl sulfoxide and 10 parts by volume of methylene chloride, made up to 125-130 ⁰ C was heated and kept under a nitrogen atmosphere in a device with which the solids could be separated and added at the same time. 20 minutes after the addition was completed by Protocatechusaldehyd and sodium hydroxide, further 2 parts by volume of methylene chloride and 0.3 parts by weight of sodium hydroxide at 125 were added to 13O ⁰ C. The reaction mixture was heated for an additional 70 minutes. In order to isolate the product, the reaction mixture was subjected to steam distillation. By extraction with ether and evaporation of the solvent, 9.15 parts by weight of piperonal F. 35 ° C. were obtained from the distillate. The product was identified by comparison with an authentic sample. The yield was 61% of theory.

45 Example 6
2,3-methylenedioxynaphthalene

The reaction was carried out as in Example 5, except that 16 parts by weight of 2,3-dihydroxynaphthalene were used. 16.3 parts by weight of 2,3-methylenedioxynaphthalene with a melting point of 99 to 100 ^° C. were obtained. The yield was 94% of theory.

A solution of 11.8 parts by weight of 3-methyl-5- ( 1,1,3,3-tetramethylbutyl) catechol and 5% by weight. Example .7

The reaction was carried out as in Example 5, except that 6.3 parts by weight of o-hydroxybenzenethiol were used. To give 1.6 parts by weight 1,3-benzoxathiol Kp. _19114-117 ⁰ C. The yield was 23% of theory.

Example 8 in vacuo and subsequent recrystallization

Purified ethanol. Mp 212-214 ° C; Yield 50% of 3,4,5,6-tetrabromo- (1,2) -methylenedioxybenzene of theory.

The reaction was carried out as in Example Ic) by weight analysis in percent for C ₇ H ₂ Br ₄ O ₂ : with the exception that 3,4,5,6-tetrabromo-

catechol was used in place of catechol. Calculated ... C 19.2, H 0.5, Br 73.0;

The product obtained was then found by sublimation .... C 19.1, H 0.6, Br72.4.

Claims (1)

Claim: Process for the preparation of benzo- or naphtho-dioxoles or -oxathiols of the general formula (D o ^/