Patent GB-427428-A (GB)
Title: Method of producing follicle hormone hydrate
IPC: C07J75/00
Filed: 1933-10-26
Abstract: Follicle hormone hydrate of the formula C18H24O3 is obtained from the hormone reduction product of the formula C18H24O2 described in Specification 428,132, by treatment thereof with an agent for splitting off water so as to produce an unsaturated phenol of the formula C18H22O and then treating this with an oxidizing agent capable of adding two hydroxyl groups to the compound at the double bond.  According to the example, the initial hormone reduction product is heated with anhydrous potassium bisulphate and the product sublimed in a high vacuum. The sublimate is dissolved in 30 per cent acetic acid and treated with hydrogen peroxide in presence of silver sulphate and acid sodium sulphate as catalysts.  The mixture obtained is diluted with water and extracted with ether, and the ether extract evaporated to yield crystals, which may be recrystallized from alcohol.  In place of hydrogen peroxide, dilute permanganate or a peracid such as perbenzoic acid may be used as the oxidizing agent. The Specification as open to inspection under Sect. 91 relates also to a process, stated to yield the same acid product, wherein the reduction products of follicle hormone are esterified with such acids, e.g. hydrobromic, hydriodic and toluene sulphonic acids, as yield esters which spontaneously decompose to give the unsaturated phenols.  These acids are preferably used in admixture with dehydrating agents such as glacial acetic acid, sulphuric acid or phosphoric acid.  The unsaturated phenols are stated to oxidize very readily, for instance, on boiling their solutions in water, aqueous salt solutions, aqueous methanol and the like, in the presence of air or oxygen.  According to an example, dihydrofollicle hormone dissolved in glacial acetic acid is mixed with a glacial acetic acid-hydrobromic acid mixture at low temperature and after standing for two days is poured into a further quantity of glacial acetic acid and the precipitate so obtained is dissolved in ether.  The ethereal solution is washed with caustic soda solution and with water and is then dried, and finally the ether is evaporated.  The product is fractionally p  crystallized from aqueous methanol, if necessary after treatment with active carbon, and yields two crystalline bodies of m.p. 120--121,5 DEG  C. and 210--213 DEG  C. respectively.  The process may be applied to dihydrofollicle hormone of m.p. 172--173 DEG  C. or to its isomer of m.p. 202--204 DEG  C., or to reduction products of equilin, hippolin and the like and of synthetic products of similar physiological properties.  This subject-matter does not appear in the Specification as accepted.ALSO:Follicle hormone hydrate of the formula C18H24O3 is obtained from the hormone reduction product of the formula C18H24O2 described in Specification 428,132, by treatment thereof with an agent for splitting off water so as to produce an unsaturated phenol of the formula C18H22O and then treating this with an oxidizing agent capable of adding two hydroxyl groups to the compound at the double bond.  According to the example, the initial hormone reduction product is heated with anhydrous potassium bisulphate and the product sublimed in a high vacuum. The sublimate is dissolved in 30 per cent acetic acid and treated with hydrogen peroxide in presence of silver sulphate and acid sodium sulphate as catalysts.  The mixture obtained is diluted with water and extracted with ether, and the ether extract evaporated to yield crystals, which may be recrystallized from alcohol.  In place of hydrogen peroxide, dilute permanganate or a peracid such as perbenzoic acid may be used as the oxidizing agent.  The Specification as open to inspection under Sect. 91 relates also to a process, stated to yield the same end product, wherein the reduction products of follicle hormone are esterified with such acids, e.g. hydrobromic, hydriodic and toluene sulphonic acids, as yield esters which spontaneously decompose to give the unsaturated phenols.  These acids are preferably used in admixture with dehydrating agents such as glacial acetic, sulphuric acid or phosphoric acid.  The unsaturated phenols are stated to oxidize very readily, for instance, on boiling their solutions in water, aqueous salt solutions, aqueous methanol and the like, in the presence of air or oxygen.  According to an example, dihydrofollicle hormone dissolved in glacial acetic acid is mixed with a glacial acetic acid-hydrobromic acid mixture at low temperature and after standing for two days is poured into a further quantity of glacial acetic acid and the precipitate so obtained is dissolved in ether.  The ethereal solution is washed with caustic soda solution and with water and is then dried, and finally the ether is evaporated.  The product is fractionally crystallized from aqueous methanol, if necessary after treatment with active carbon, and yields two crystalline bodies of m.p. 120-121.5 DEG  C. and 210-213 DEG  C. respectively.  The process may be applied to dihydrofollicle hormone of m.p. 172-173 DEG  C. or to its isomer of m.p. 202-204 DEG  C., or to reduction products of equilin, hippolin and the like and of synthetic products of similar physiological properties.  This subject-matter does not appear in the Specification as accepted.