Process for selective mono-debromination of polybromoalkyl aryl or heteroaryl ketones
AssigneeMerck & Co., Inc.
InventorAnthony O. King
Life of this patent
Estimating the term…
Abstract
A process for selectively debrominating polybromoalkyl aryl ketones and polybromoalkyl heteroaryl ketones is disclosed. The process comprises contacting an alpha-polybrominated ketone with an alkali metal sulfite in the presence of a C2-C6 alkylcarboxylic acid to obtain a selectively mono-debrominated product.
Claims20
A selective mono-debromination process which comprises contacting an alpha-polybrominated ketone selected from a compound of Formula I and a compound of Formula II:
- with an alkali metal sulfite in the presence of a C2-C6 alkylcarboxylic acid to obtain a selectively mono-debrominated product, wherein:
- Y is aryl or heteroaryl having at least one ring heteroatom selected from O and S;
- R1 is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, nitro, cyano, SO2Ra, or CO2Ra;
- R2 is hydrogen, bromo, or C1-C6 alkyl;
- Ra is C1-C6 alkyl;
- and
- p and q are each independently integers from 0 to 4.
A process for preparing a dibromomethyl ketone of Formula V:
- wherein:
- Y is aryl or heteroaryl having at least one ring heteroatom selected from O and S;
- R1 is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, nitro, cyano, SO2Ra, or CO2Ra;
- Ra is C1-C6 alkyl;
- and
- p is an integer from 0 to 4;
- wherein the process comprises:
- (A) brominating a methyl aryl or heteroaryl ketone to obtain a reaction mixture comprising di- and tri-bromomethylketones of Formulas V and VI:
- and
- (B) contacting the reaction mixture obtained in (A) with an alkali metal sulfite in the presence of a C2-C6 alkylcarboxylic acid to selectively monodebrominate the tribromomethyl ketone.
A process for preparing an alpha-monobromoalkyl ketone selected from a ketone of Formula VI and a ketone of Formula VII:
- wherein:
- Y is aryl or heteroaryl having at least one ring heteroatom selected from O and S;
- R1 is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, nitro, cyano, SO2Ra, or CO2Ra;
- R2 is hydrogen or C1-C6 alkyl;
- Ra is C1-C6 alkyl;
- and
- p and q are each independently integers from 0 to 4;
- wherein the process comprises:
- (A) brominating an alkyl aryl or heteroaryl ketone selected from a ketone of Formula VIII and a ketone of Formula IX:
- to obtain a reaction mixture comprising mono- and di-bromoalkyl ketones selected from (i) ketones of Formula I and Formula VI:
- and (ii) ketones of Formulas II and VII:
- and
- (B) contacting the reaction mixture with an alkali metal sulfite in the presence of a C2-C6 alkylcarboxylic acid to selectively monodebrominate the dibromoalkyl ketone to the alpha-monobromoalkyl ketone.
Dependencies are inferred from the claim text.