Patent GB-1058857-A (GB)
Title: Tetrahydrofuranol derivatives
Inventor: YEOWELL HEATHER NINA GRANT NOW
IPC: C07D307/32
Filed: 1964-07-17
Abstract: Novel tetrahydrofuranol derivatives of general formula <FORM:1058857/C2/1> wherein R1 is a methyl or ethyl group and R2 is an ethyl or propyl group, R1 being ethyl when R2 is ethyl, and one of R3 and R4 represents a hydrogen atom and the other represents a hydroxy carbamoyloxy or N-monomethylcarbamoyloxy group are prepared (a) by reducing by methods known per se for the reduction of ketones to secondary alcohols a ketone of the above formula in which one of R3 and R4 is a keto group, and the other is hydrogen, and (b) by a known method for reducing unsaturated ketones, the ethylenic and ketone group of a 2,3-dihydrofuran-3-one of the general formula <FORM:1058857/C2/2> wherein R1 and R2 have the above significance and, in either case, if required, converting the resulting hydroxy compound into a monosubstituted or unsubstituted carbamoyloxy derivative by methods known per se including reacting the tetrahydrofuranol with (a) phosgene to form the corresponding chlorocarbonate and reacting this compound with ammonia or monomethylamine, and (b) phenylchloroformate to form the corresponding phenylcarbonate and reacting this compound with ammonia or monomethylamine.  2,5-Dihydroxy-compounds of the general formula <FORM:1058857/C2/3> wherein R1 and R2 have the above significance are prepared by reacting 3-hydroxy-3-R1R2-prop-l-yne with acetaldehyde, or by reacting the Grignard complex of 3-hydroxy-but-l-yne with a ketone R1R2C=O, R1 and R2 being as defined above, or by reacting CH3-CH(OH)-C­CH and R1R2C=O in the presence of strong base.  3 - Hydroxy - 3 - R1R2 - prop - 1 - yne, wherein R1 and R2 have the above significance, is prepared by reacting acetylene with ketones R1R2C=O in liquid ammonia, in the presence of sodamide, or in inert organic medium in the presence of strong base.  5 - Hydroxy - 5 - R1R2 - penta - 1,3 - diyne is prepared by reacting the monosodium derivative of diacetylene with R1R2C=O.  4 - Ethynylmethylene - 3,3 - R1R2 - 1 - R5R6-dioxolan is prepared by reacting the previously mentioned compound with R5R6C=O where R5 and R6 are hydrogen or alkyl, in the presence of an alkali metal carbonate in an inert organic medium, R1 and R2 are as hereinbefore defined.  3 - Ethyl - 3 - hydroxy - pent - 1 - yne is prepared by reacting acetylene and acetaldehyde. Compounds of the first general formula above wherein one of R3 and R4 represents a keto group and the other a hydrogen atom are prepared by cyclizing <FORM:1058857/C2/4> wherein R1 and R2 have the above significance by treatment with mercuric sulphate, or mercuric acetate in the presence of sulphuric acid, or with boron trifluoride in a lower alkyl ether in the presence of red mercuric oxide and trichloroacetic acid in a lower alkanol.  2,3 - Dihydro - furan - 3 - ones of the second general formula above are prepared by treating the previously mentioned dioxolons with a strong acid.  Pharmaceutical compositions having hypnotic and anaesthetic activity and which may be administered orally or parenterally in the form of compressed tablets, pills, dispersible powders, or granules, or as emulsions, solutions, suspensions, syrups or elixirs, contain a compound of the first general formula above as the active ingredient.