CS269565B1 - 3-alkoxymethyl-4-hydroxyphenylalkyl ketones and a process for their preparation - Google Patents

Abstract

The solution concerns the new 3-Alkoxy- . and methyl 1-4-hydroxyphenylalkylketones generally of the formula I, in which R1 is alkyl with 1 to 12 carbon atoms, R2 is alkyl 3 in a linear chain with 1 to 19 carbon atoms, alkyl with | branched chain and 3 to 5 carbon atoms; ka and alkenyl with 3 carbon atoms i method J of preparation by reaction of 4-hydroxy-3-chloromethylphenyl-j nylalkyl ketones II with the corresponding alcohol ! III in sodium bicarbonate medium. 1; Compounds of this type can be used as starting materials for the preparation of biologically active substances.

Description

The invention relates to 3-alkoxymethyl-4-hydroxyphenylalkyl ketones of the general formula I. OH

CH ₂ OR ² (COR ¹

- I 2 where R is alkyl with 1 to 2 carbon atoms, R is straight chain alkyl with 1 to 10 carbon atoms, branched chain alkyl with 3 to 5 carbon atoms and alkenyl with 3 carbon atoms.

Substances of general formula I are derivatives of p-hydroxyacetophenone or of p-hydroxypropiophenone and are used in the preparation of substances with biological properties (in the preparation of beta-adrenolytics, antiarrhythmics and local anesthetics). The substances themselves, mainly with a higher alkyl chain, show a certain antimicrobial activity against the Staphylococcus aureus strain

3-Alkoxymethyl-4-hydroxyphenylalkylketones of general formula I can be prepared according to the invention by leaving the corresponding 4-hydroxy-3-chloroethylphenylalkylketones of general formula II, where R^ means the same as in formula I, prepared according to the literature Trave R., Gazz. Chem. Italian. 81, 773 (1951)., Sohda S., Hasatashi F., Tomazo T., Norujasu H., J. Med. Chem. 22, 279 /1979/ .OH CH ₂ C1

T COR ¹ reacts with the corresponding alcohol of general formula III R ² -O-H

III where R is the same as in formula I, in the presence of NaHCOj by a modified procedure according to Sohda S., Masatashi F., Tomazo T., Norujasu H., □..Med. Chem. 22, 279 /1979/ More details follow from the following method of preparation Example: 4-hydroxy-3-propoxymethylphenylmethylketone.

0.14 mol of 4-hydroxy-3-propoxymethylphenylmethylketone is dissolved in 150 ml of 1-propanol at laboratory temperature and 0.29 mol of NaHCO- is gradually added. The mixture is left to react for ⁴ hours at room temperature and then heated for 4 hours at 30-40 C. After filtering off NaHCO 3 and distilling off the excess alcohol under reduced pressure, the oily residue is recrystallized from heptane or hexane.

4-hydroxy-3-propoxymethylphenylmethyl ketone, white crystalline substance is formed in a yield of % of theory, 1.1. 52-3°C.

Elementary analysis for ^12^16^3 Calc. /Found

C 69.21 /69.22

H 7.74 /7.87

IR - spectral characteristics 3 220 cm \ ςθ 1 686 cm qq 1615 cm ^-NMR Ar OH =8.37 /lH,s/., Ar-CH ₂ 0 = 4.6 /2H,é/., CHy-C = 2.40 /3H,s/., -~ O

_CH3 - _CH2 =0.85 (3H,t)

Using the mentioned procedure, the following previously undescribed substances are prepared:

1. 3-ethoxymethyl-4-hydroxyphenylmethyl ketone, m.p. 64-5°C /cyclohexane/

2. 4-hydroxy-3-propoxymethylphenylmethylketone, m.p. 52-3°C /n-hexane/

CS;269565 Bl

3. 4-hydroxy-3-isopropoxymethylphenylmethylketone, m.p. 70-3°C /n-hexane/

4. 3-Allyloxymethyl-4-hydtoxyphenylsiethyl ketone, m.p. 38-40°C, /n-hexane/

5. 3-butoxymethyl-Λ-hydroxyphenylmethyl ketone, m.p. 53-4°C /n-hexane/

6. 4-hydroxy-3-isobutoxymethylphenylmethylketone, m.p. 40-3°C /n-hexane/

7. 4-hydroxy-;-sec. butoxymethylphenylmethylketone, m.p. 42-4°C /n-hexane/

8. 4-Hydroxy-o-pentoxyaethylphenylmethylketone, m.p. 34-5°C /n-hexane/

9. 4-Hydroxy-3-isopentoxymethylphenylmethylketone, m.p. 47-8°C /n-hexane/

10. 3-hexyloxynethyl-4-hydroxyphenylmethyl ketone, m.p. 41-3°C /n-hexane/

11. 3-Heptyloxynethyl-4-hydroxyphenylmethyl ketone, m.p. 60-2°C /n-hexane/

12. 4-hydroxy-3-octyloxymethylphenylmethylketone, m.p. 44-5°C /n-hexane/

13. 4-hydroxy-3-nonyloxymethylphenylmethylketone, m.p. 45-7°C /n-hexane/

14. 4-hydroxy-3-methoxyaethylphenylethyl ketone, m.p. 78-80% /n-hexane/

15. 3-ethoxy»ethyl-4-hydroxyphenylethyl ketone, m.p. 65-7°C /n-hexane/

16. 4-Hydroxy-3-propoxy«ethylphenylethylketone, m.p. 61-3°C /n-hexane/

17. 4-hydroxy-3-isopropoxymethylphenylethyl ketone, m.p. 73-5°C /n-hexane/

18. 3-allyloxymethyl-4-hydroxyphenylethyl ketone, m.p. 35-7°C /n-hexane/

19. 3-butoxymethyl-4-hydroxyphenylethyl ketone, m.p. 68-70°C /n-hexane/

20. 4-Hydroxy-7-3ec. butoxymethylphenylethyl ketone, m.p. 42-4°C /n-hexane/

21. 3-hexyloxynethyl-4-hydroxyphenylethyl ketone, m.p. 51-3°C /n-hexane/

22. 3-heptyloxymethyl-4-hydroxyphenylethyl ketone, m.p. 45-7°C /n-hexane/

23. 4-hydroxy-3-octyloxymethylphenylethyl ketone, m.p. 54-7°C /n-hexane/

24. 4-hydroxy-3-nonyloxymethylphenylethyl ketone, m.p. 59-61°C /n-hexane/

25. 3-decyloxyethyl-4-hydroxyphenylethyl ketone, m.p. 52-5°C /n-hexane/

Claims (2)

SUBJECT OF THE INVENTION 1 · ¹ 2 · where R is alkyl of 1 to 2 carbon atoms, R is straight chain alkyl of 1 to 10 carbon atoms, branched chain alkyl of 3 to 5 carbon atoms and alkenyl of 3 carbon atoms. 1. 3-Alkoxymethyl-4-hydroxyphenylalkyl ketones of the general formula I , OH ch ₂ or ² 2. Method for the preparation of 3-Alkoxymethyl-4-hydroxyphenylalkylketones of the general formula I according to point 1, characterized in that the 3-chloromethyl-4-hydroxyphenylalkylketone of the general formula II is allowed to react with ch ₂ ci COR ¹ where r! is a carbon chain with 1 to 2 carbon atoms with the corresponding alcohol of general formula III -OH CS 269565 B1 where R is the same as in formula I in the presence of an alkaline bicarbonate, preferably sodium bicarbonate, at a temperature of 30-40°C.