α-(4,6-Diphenyl-2-oxo-1-pyridyl)benzyl-lithiums and their reactions with electrophiles

Abstract

1 -Benzyl-4,6-diphenyl-2-pyridone is lithiated by LiNPrl, at the methylene carbon to form a carbanion which reacts with various electrophiles to give the corresponding 1 -(a-substituted-benzyl)-4,6-diphenyl-2-pyridones. Potassium dimsylate converts 1 -benzyI-4,6-diphenyl-Z-pyridone into the 3-methyl derivative, The anion derived from 1 -(a-methylbenzyl) -4,6-diphenyl-2-pyridone rapidly rearranges to the azepinone (1 8).HYDROGEN atoms on sP3-carbon attached to nitrogen arc rendered acidic if the nitrogen also carries a carbonyl group as demonstrated by Durst,l who lithiated (1) to give (2) as shown by the formation of (3) 011 rapid quenching with D,O. Beak similarly lithiated (4), but the product isolated was ketone (6) arising from rapid reaction with more (4). Such self-condensation was prevented by Seebach in the anion (7) of the isopropyl derivative (5) or in NNdimethyltriplienylacctamide. NNDi benzyl-benzamide and N-benzylhenzamide 5 have also been successfully lithiated (the latter requiring two equivalents of base) and all these carbanions reacted to give the expected products with electrophiles such as alkyl halides, aldehydes, ketones, and esters. Seebach and Schlecker have metallatecl N-methylsuccinimides a t the methyl group, but considerable steric hindrance around the carbonyls by Csubstituents is required to reduce diiner formation. MeEMe2 PhCONMeCHt COPh'CHRPh 0 0 ( 6 ) 0 ( 7 1We reasoned that N-alkylated lictc\roarom;itic carbony1 conipounds should also be capable of a-metal1 a t ' ion and that the considerable aromatic stabilisation of compounds such as pyridones 7 could be advantageous.Our initial experiments centred on cornpounds of type (8) which were prepared in fair to good yield from the corresponding amine and 4,6-diphenyl-2-pyrone (9) itself available in one moderate-yield step from commercial benzoylacetic ester. Alternatively, l-sub-5 New permanent address; Department of Chemistry, University of Florida, Gainesville, Florida, 1J.S.h. stituted 4,6-diplienyl-2-pyridoiles can be prepared via the corresponding 1-substituted 2-methyl-4,6-diphenylpyridiniuin cations.*O In compounds of type (8) the phenyl groups sliould discourage nucleophilic attack at ringPh fi0 I RC H, Ph (io ( 9 ) z = o (101 Z = N -0-a ; R = Ph c ; R = p -MeOC6H4 d ; R = p -MeC6H4 b ; R = u-CLCCH, carbon and the anions (11) resemble their oxygen analogues (10) which can readily be alkylated.llilfctallatioiz TeclzItiqu~s.-Potassium t-butoxide in diniethylformamide and sodium hydride in tetrahydrofuran did not react with 1-benzyl-4,6-diplienyl-2-pyridone (8). Treatment with potassium dimsylate in dimethyl sulplioxide at 60 "C formed a highly colouretl reaction mixture, indicative of anion formation, but subsequent treatment with an electrophile, such as 4-toluoaldehyde, gave as the only product identified 1-bcnzyl-3-methy1-4,6-diphenyl-2-pyridone (24:/0, unoytimised). We suggest that this product is formed by initial reagent addition to give (12) followed by the pathway (12)-+( 1 3 ) 4 14). The nearest heterocyclic analogies ...

Direct conversion of long-chain carboxamides to alkylammonium tosylates with hydroxy(tosyloxy)iodobenzene, a notable improvement over the classical Hofmann reaction

“…Thus, amine yields of nearly 50% from lauramide (R = Cu) and tridecanamide (R = C12) with hypochlorite in 33% dioxane have been reported, but it was noted in the same paper that "a run with palmitamide was a complete failure".4 Until now, the indirect procedure of Jeffreys has been the method of choice for the production of amines from long-chain amides; in methanolic hypohalite, the amides give urethanes 3 from which the amines can be liberated by hydrolysis.2,4-6 RCONH2 RNHCONHCOR RNHCOOCHa In recent years, the utility of hypervalent organoiodine compounds as Hofmann reagents has been recognized.7-10 However, except for one example (R = Cu, 57% yield),10 they have not been applied to long-chain amides. Our efforts have focused on hydroxy(tosyloxy)iodobenzene (4, HTIB), which reacts with carboxamides in acetonitrile to give alkylammonium tosylates (eq l).10 Such transfor-RCONH2 + PhI(OH)OTs 4, HTIB MeCN RNH3+, OTs-+ Phi (1) mations proceed through intermediate IV-phenyliodoniocarboxamide tosylates 5 and their collapse to alkyl isocyanates 6, p-toluenesulfonic acid, and iodobenzene.11…”

Seven‐Membered Heterocycles: Azepines, Benzo Derivatives and Related Systems

“…In both cases the isolated 4H-azepines are prone to isomerization to the more stable 3H-isomers. A substituted 2-pyridone has also been transformed into the 3H-azepinone 118 by treatment with LDA (Scheme 21.20) [139].…”