N

R"

Scheme 22

A nucleophilic group in the main side chain intervenes in the process via intramolecular addition, as happens with the tranquilliser proxibarbital (59d, R=allyl, R-2-hydroxypropyl) which gives the tetrahydrofuranone (63) ( Scheme 23).75

The second general reaction is dealkylation to give products (64) (path c), and this is the main path followed when one of the substituents is a stabilised alkyl group (secondary or allylic). This is the case with pentobarbital (59e, R=Et, R-2-pentyl, R'-H)76 and secobarbital (59f, R=allyl, R'=2-pentyl, RM=H) (Scheme 22).77

This general scheme holds for the monoanion (the predominant species at pH 10), and the acidity of the medium affects to some extent the product distribution.75' 76> 78> 79 A different process occurs for the acidic form of cyclobarbital (59g, R=Et, R-l-cyclohexyl, R"=H),80 which is photo-oxidised to the ketone (65) rather than cleaved (Scheme 23). Monoalkylbarbiturates (64) undergo hydroxylation at position 5 to give products (66) (see Scheme 22).76 The 2-thio analogue of phénobarbital (67) gives (68) by selective reduction of the thiocarbonyl function by irradiation in alcohols (Scheme 24).81

LVN" PRhr,

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