Patent GB-627839-A (GB)
Title: Improvements in the production of benzofuranone derivatives
Filed: 1946-03-06
Abstract: Benzofuranone compounds of the general formula <FORM:0627839/IV (b)/1> wherein X represents one or more hydrogen, halogen or hydrocarbon substituents, e.g. chlorine or n-propyl, said hydrocarbon substituents may be in the form of a cyclic group fused to the benzene ring, R1 represents hydrogen, or a substituted or unsubstituted hydrocarbon radical, and R2 is a radical containing a nitrogen atom bonded to the benzofuranone ring by a branched, unbranched or substituted aliphatic hydrocarbon chain containing up to eleven carbon atoms, are prepared (i) by introducing the group R2 into a compound of the general formula <FORM:0627839/IV (b)/2> wherein X and R1 have the above significance, by replacing the hydrogen atom with an alkali metal and reacting the product with an R2-halide, or (ii) starting with a compound containing the benzene ring substituted with groups on adjacent carbon atoms from which the furanone ring is formed, namely, a group -OR0, wherein R0 is a group replaceable by hydrogen in hot acid or alkali, and a group comprising a carbon atom which is attached to the benzene ring, and the remaining valencies are satisfied by two hydrogen atoms and a cyanogen group, introducing the group R2 by replacing one of the hydrogen atoms in the starting compound with an alkali metal and reacting with an R2-halide, repeating the procedure to introduce the group R1 when it does not represent hydrogen, treating the resulting product with acid or alkali to replace the group R0 with hydrogen and to convert the cyano group to a carboxyl group, and eliminating water between the resulting carboxyl and hydroxyl groups to form the furanone ring.  The group R2 may be an amino or acylamino group or a nitro, cyano or hydroxylamino group or a heterocyclic group.  When the product obtained by adding an R2 group to the benzofuranone compound contains a basic amino group, the resulting compound and the inorganic salt formed by the addition of the R2 group are extracted with dilute aqueous acid, the extract is made alkaline and the desired compound is then extracted with an organic solvent.  A dehydrating agent, e.g. thionyl chloride, may be used to eliminate water in method (ii) above, and is then removed, and the resulting product is taken up in an organic solvent and water at 0 DEG  C., the aqueous layer is made alkaline and the desired product extracted with an organic solvent.  The benzofuranone compounds containing a basic amino group may be converted to salts by treatment with a non-toxic acid, e.g. sulphuric, phosphoric, hydrochloric, levulinic, mucic, acetic or tartaric acid, or they may be converted to quaternary salts by treatment with an alkyl chloride or bromide when they contain a tertiary amino group.  When the group R2 represents a nitro, cyano, hydroxylamino or acylamino group in the required benzofuranone compound, it may be converted to an amino group, e.g. by reduction. A number of examples are given.  3 - Phenyl - 5 - n - propyl - and 3 - m - tolyl - 2(3)-benzofuranone are prepared by heating p-n-propylphenol and mandelic acid and m-methyl-mandelic acid and phenol respectively.  The Specification as open to inspection under Sect. 91 refers to the preparation of compounds of the general formula <FORM:0627839/IV (b)/3> by the methods given above.  R4 and R5 form a chain of carbon atoms, R1 represents hydrogen or substituted or unsubstituted hydrocarbon radical, R2 is a group containing a nitrogen atom and at least one carbon atom adjacent the furanone ring and X has the above significance.  The group R2 may be of the type <FORM:0627839/IV (b)/4> wherein R6, R7, R8, R9, R10 and R11 may each be hydrogen, hydroxy, halogen or hydrocarbon, R12 a group containing the nitrogen atom, and m, n and p individually zero or a small whole number, but not all zero.  3 - (b  - diethylaminoethyl) - 3 - phenyl - 2(3) - hexahydrobenzofuranone is prepared by refluxing benzyl cyanide with sodamide and reacting the resulting sodium salt of benzyl cyanide with b -diethylaminoethyl chloride to yield b -diethylaminoethylbenzyl cyanide, and the sodium derivative thereof formed by reaction with sodamide is reacted with cyclohexene oxide to give a  - (2 - hydroxycyclohexyl) - a  - (b  - diethylaminoethyl) benzyl cyanide which is hydrolysed with hydrobromic acid, and water eliminated between the hydroxy group and the resulting carboxyl group to form the furanone ring.  3 - Amino - 3 - phenyl - 2(3) - benzofuranone hydrochloride is prepared by heating a mixture of thionyl chloride and a -phenyl-a -(o-hydroxyphenyl)-a -aminoacetic acid hydrochloride.  This subject-matter does not appear in the Specification as accepted.