CS209290B1 - 1-/3-chlorphenoxy/-3-butyn-2-ol and method of its manufacture - Google Patents

Description

(54) 1- (3-chlorophenoxy) -3-butin-2-ol and a process for its preparation

The present invention provides 1- (3-chlorophenoxy) -3-butin-2-ol and a process for its preparation.

It is known from the literature that the alkylation of the phenolate with chloroacetal is slower than that of thiophenolate (Autenrieth W .: Ber 24 (1891)). In the synthesis of the subject matter of the present invention, it has been found that said alkylation proceeds even more slowly with the 3-substituted phenolates, presumably due to the 3-chlorine atom to the hydroxyl function. Since the alkylation of 3-chlorophenolate or 3-chlorophenol in an alkaline medium with chloroacetal has not yet been described, it was necessary to find the reaction conditions for this alkylation. Hydrolysis of 2a 4-chlorophenoxyacetaldehyde acetate to the corresponding aldehyde is known (U.S. Pat. No. 2,629,741), but not with the 3-chloro derivative. The preparation of 1- (3-chlorophenoxy) -3-butin-2-ol has not been described in the literature.

The present invention provides a process for the preparation of 1- (3-chlorophenoxy) -3-butin-2-ol of formula (I)

starting from the reaction of an alkali metal salt of 3-chlorophenol with methyl or ethylacetal chlorine or bromine 209290 acetaldehyde at a temperature of 85 to 200 ° C in a closed vessel in an alcohol corresponding to the acetal used to give the acetal of the 3-chlorophenoxyacetaldehyde II

Cl

OOCH CH (OR), ( ⁿ )> 9 - Z wherein R is methyl or ethyl. Hydrolysis of the acetal of formula (II) under acidic conditions releases it

3-chlorophenoxyacetaldehyde of formula ΠΙ

(ΠΙ) treated with an acetylene metal salt such as acetylene magnesium bromide in an anhydrous ether solution such as tetrahydrofuran at 0 to 50 ° C. Subsequent decomposition with water or ammonium chloride solution gives 1- (3-chlorophenoxy) -3-butin-2-ol of formula I.

The process for the preparation of the butinol of the formula I according to the invention makes it possible to prepare a substance which may be an intermediate in the production of the prostaglandin analogue F ₂ a, the so-called "estrumate" of the formula IV

which is important for its biological effects in the production of cattle, sheep and pigs as _one heat regulator (Crossley NS: Chem. Ind. 1976,

334). The synthesis is based on available raw materials,

3-chlorophenol, acetal and ACE haíogenacetaldebydu> ^f mesitylene. The first two steps of the synthesis are very simple, with good, preparatively significant yields. The compounds of formula (II) and (III) are isolated simply, in the final phase, simply by distillation under reduced pressure, the resulting product of formula (I) requiring purification and filtration through a silica gel column. The phenoxybutinol of the formula I is crystalline, stable for long periods of storage preferably in the absence of light and air. Its assumed structure is confirmed by elemental analysis, infrared and 1 H-NMR spectra. The production process is described in more detail in the following examples.

Example

A solution of 60.2 g (0.4 mol) was placed in the autoclave

Sodium 3-chlorophenolate (prepared by dissolving 3-chlorophenol in an equimolar amount of 10% sodium hydroxide solution and evaporating to dryness and drying under reduced pressure to constant weight) and 64 g (0.42 mol) of monochloroacetamide diethylacetal in 300 ml of ethanol. The reaction mixture was heated to 190 ° C over 2 hours and heated to 190-200 ° C for 14 hours. After cooling, most of the ethanol was distilled off from the reaction mixture under reduced pressure, and 250 ml of ether was added to the residue. The ethereal solution was washed 3 times with 100 ml of 5% sodium hydroxide solution, once with 100 ml of water and dried

And anhydrous potassium carbonate. After removal of desiccant and ether, the residue was distilled under reduced pressure. 62 g (63% of theory) of 3-chlorophenoxyacetaldehyde diethyl acetal, boiling at 155 DEG-156 DEG C./36 mbar, were isolated. For C ₁₂ H _{17 and} O ₃ (mol% 244.7) calculated: 58.90% C, 7.00% H, 14.49% Cl; Found: C 59.24, H 7.19, Cl 14.63.

Example 2

In a solution of sodium methoxide prepared by dissolving 9.2 g (0.4 gmol) of sodium in 250 ml of methanol, 51.44 g (0.4 mol) was dissolved

3-chlorophenol and then 52.3 g (0.42 mol) of chloroacetaldehyde dimethyl acetal are added. The reaction mixture was autoclaved as described in Example 1. After isolation as described in the previous example, 52 g (60%) of dimethyl acetal were obtained.

3-chlorophenoxyacetaldehyde, boiling point 143 DEG-144 DEG C./15 mm Hg. For C 10 H ₁₃ ClO ₃ (moL mass 216.7) calculated: 55.43% C, 6.05% H, 16.36% a; Found: C, 55.20. 6.28% H, 16.52% a.

Example 3

To 350 ml of water was added 0.5 g of p-toluenesulfonic acid »36.6 g (0.15 me4) of 3-chloro-methoxyaleadehyde diethyl acetal, and the mixture was heated at reflux for 6 hours. The liberated aldehyde was distilled from the mixture with steam and the distillate was shaken 3 times with 100 ml of ether. The combined ether extracts were washed first with 50 ml saturated sodium carbonate solution, then 3 times with 70 ml water each. After drying the ethereal solutions with magnesium sulfate overnight in the refrigerator and distilling off the ether, the product was isolated after two distillations.

19.6 g (76.8%) of 3-chlorophenoxyacetaldehyde, boiling point 89-9 ° C / 27 Pa. For C ₈ H ₇ O ₂ (moL mass 170.6) calculated: 56.32% N, 4.20% K 20.79% Cl; found. C 56.53, H 4.44, Cl 20.35.

J

Example 4

A solution of Grignard reagent was prepared from 4.8 g (0.2 gmol) of magnesium and 16.3 g (0.15 mol) of ethyl bromide in 100 ml of tetrahydrofuran, which was poured from unreacted magnesium into a separatory funnel and added under stirring for 3 to 5 ml portions to 140 ml tetrahydrofuran, saturated after each dose of acetylene reagent at 10 to 20 ° C. The reaction mixture was cooled in an ice bath and a solution of 17 g (0.1 mol) of 3-chlorophenoxyacetaldehyde in 20 ml of tetrahydrofuran was added dropwise. After stirring at 20 ° C for 15 hours, a saturated aqueous solution of 10.7 g (0.2 mol) of ammonium chloride was added dropwise to the reaction mixture. After pouring the tetrahydrofuran solution and washing the inorganic salts with the same solvent, tetrahydrofuran was distilled off and the residue (21 g) was applied in a benzene solution onto a 150 g silica gel column washed with 1: 1 chloroform-benzene. The last, most popular fraction was isolated 1- (3-chlorophenoxy) -3-but-2-ol in a yield of 8.75 g (44.5%) as a colorless oil which crystallized the next day and melted at 37-39. Deň: 32 ° C. For C ₁₀ H ₉ ClO ₂ (mol. Weight 196.6) calculated: 61.02% C, 4.62% H, 18.03% Cl; Found: C 61.33, H 4.71, Cl 18.28. Infrared spectrum:

680,910,1 045,1 070,1 132,1 310,1 430,1 480, 1 597, 2 130, 3 320, 3 600 cm ^-1 ; 1 H-NMR spectrum (δ-values): 2.49-2.70; 3.98-4.24; 4.68-4.90; 6.72-7.06; 7.06-7.36.

Claims (3)

SUBJECT OF THE INVENTION 1. 1- (3-chlorophenoxy) -3-butyne- 2-ol of formula I; Process for the preparation of 1- (3-chlorophenoxy) -3-butin-2-ol of the formula I according to claim 1, characterized in that the alkali metal salt of 3-chlorophenol is alkylated with chloroacetaldehyde or bromoacetaldehyde methyl acetal or ethyl acetate at 85 to 200 ° C. in an alcohol solution corresponding to the haloacetaldehyde acetal used in a sealed vessel to form 3-chlorophenoxyacetaldehyde acetal community; Π Oh ₂ ch / or / ₂ (D)> wherein R is methyl or ethyl, which hydrolyzed under acidic conditions to give the 3-chlorophenoxyacetaldehyde of formula III, from which reaction with an acetylene metal salt, for example, a Grignard reagent or sodium acetylide, yields the resulting compound of formula I. 3. The process according to claim 1, wherein the reaction of 3-chlorophenoxyacetaldehyde with the Grignard reagent is carried out in a cyclic ether as a solvent, for example tetrahydrofuran.