Patent GB-804125-A (GB)
Title: Derivatives of 4-hydroxycoumarin and their production
IPC: C07D311/54
Filed: 1956-09-03
Abstract: The invention comprises 4-hydroxycoumarin derivatives of the general formula <FORM:0804125/IV (b)/1> wherein R1 is a hydrogen atom, an alkyl or alkoxy radical containing not more than 4 carbon atoms or a halogen atom, R2 is an alkyl radical containing not more than 4 carbon atoms and R3 is an alkyl or alkoxy radical containing not more than 4 carbon atoms or a halogen atom, and R3 stands in either the 6 or 7 position of the coumarin ring.  The novel compounds may be prepared by reacting a styryl alkyl ketone of the formula R1.C6H5.CH = CH.CO.R2 with the appropriate R3-substituted-4 hydroxycoumarin at elevated temperatures, such as from 50-200 DEG  C.  The reactants may be melted together with or without alkaline condensation agents or they may be heated in an indifferent solvent such as benzene, toluene, xylene or chlorobenzene, preferably with a basic condensation agent such as an alkali metal or alkaline earth metal alcoholate, alkali metal acetate, trisodium phosphate, or an amine such as piperidine or diethylamine.  Alternatively the reactants may be heated in a basic organic solvent such as pyridine, quinoline or dimethylaniline.  Suitable styryl alkyl ketones are those in which R1 is chloro, methoxy, ethoxy, methyl or ethyl and R2 is methyl.  The preferred 4-hydroxycoumarines are the 6- or 7-chloro, alkyl or alkoxy-derivatives.  These latter compounds may be obtained as described in Specification 705,316, by condensation of substituted 2-hydroxyacetophenones with the diethyl ester of carbonic acid in the presence of sodium alcoholate, metallic sodium or sodium hydride. Examples describe the preparation from the appropriate styryl alkyl ketone and substituted 4-hydroxycoumarin of products of the above general formula in which R1 is Cl, R2 is CH3 and R3 is Cl in pos. 7; R1 is H, R2 is CH3 and R3 is Cl in pos. 7; R1 is CH3, R2 is CH3 and R3 is Cl in pos. 7; R1 is H, R2 is CH3 and R3 is Cl in pos. 6; R1 is H, R2 is CH3 and R3 is CH3O in pos. 7; R1 is Cl, R2 is CH3 and R3 is CH3O in pos. 7; R1 is H, R2 is CH3 and R3 is CH3 in pos. 6; R1 is Cl, R2 is CH3 and R3 is CH3 in pos. 6; R1 is Cl, R2 is CH3 and R3 is CH3 in pos. 7; R1 is CH3O, R2 is CH3 and R3 is CH3 in pos. 7.  The preparation of 6-chloro-4-hydroxycoumarin by reaction of 5-chloro-3-hydroxyacetophenone and diethyl carbonate in the presence of sodium hydride in toluene is also described.  The new 4-hydroxycoumarin derivatives are suitable as rodenticides and anticoagulants (see Group VI).ALSO:A rodenticidal composition comprises a 4-hydroxycoumarin derivative of the general formula <FORM:0804125/VI/1> wherein R1 is a hydrogen atom, an alkyl or alkoxy radical containing not more than 4 carbon atoms or a halogen atom, R2 is an alkyl radical containing not more than 4 carbon atoms, and R3 is an alkyl or alkoxy radical containing not more than 4 carbon atoms or a halogen atom in either the 6 or 7 position of the coumarin ring, together with a liquid or solid carrier.  Water is a suitable liquid carrier, and talc, bentonite, chalk, or charcoal are suitable solid carriers.  The composition may be administered to rodents by adding to foods or drinking water.  The baits can contain flour, oats, bread or other inert materials, and the compounds may be used in the presence of dyestuffs or hydrophobic substances such as stearic acid and higher melting waxes.  Mixtures of the active compounds may be used, e.g. 3-(a -(p-chlorophenyl) - b  - acetyl - ethyl) - 7 - chloro - 4 - hydroxycoumarin and 3 - (a  - phenyl - b  - acetylethyl)-6-chloro-4-hydroxycoumarin when used together exhibit a synergistic effect, the preferred ratio of the compounds being 1 : 1. The active ingredients may also be used with other anti-coagulants, such as dicumarol, 2-pivalyl indanedione-1,3.  3-(a -phenyl-b -acetyl-ethyl)-4-hydroxycoumarin or phenylindanedione.  In an example, 7-chloro-4-hydroxycoumarin and 4-chlorobenzylidene acetone are heated together and the melt (7-chloro-3-(a -(4-chlorophenyl)-b -acetyl-ethyl) -4-hydroxycoumarin) is stirred with talcum and the mixture can be used as active ingredient for the production of rodenticidal baits.  (For preparation of the 4-hydroxycoumarin derivatives, see Group IV (b).)