Anhydrides with enamines

A great number of N-substituted 4-hydroxy-3-nitro-l,8-naphthyridin-2 (IH)-ones are obtained by reaction of N-substituted azaisatoic anhydrides with ethyl nitroacetate carbanion (Section II,A,4,a). A very specific method, more recently developed, is that of the inverse Diels-Alder method, involving the reactions of enamines with 5-nitropyrimidine (Section II,A,4,b). 

The 1,2,4-triazine ring is an ambident electrophile, and reacts with enamine-type nucleophiles. For example, addition of enamine 78 to a solution of triazine 77 in acetic anhydride furnished the pyrrolotriazine 31 (Equation 24) <2003TL2421>. 

In a similar way /V-(2-pyridyl)formimidates 187 (R = H, 3-Me) in methylene chloride were reacted with chloroketene 195, prepared from the appropriate carboxylic acid with trifluoroacetic anhydride followed by treatment of the mixed anhydride with triethylamine in situ, to give 3-ribofuranosyl-2-ethoxy-4//-pyrido[l,2-a]pyrimidin-4-ones 196 (R = H, 3-Me) and enamine 197 in 10—17% yields, respectively (84MI3 85CPB2671). 

Imines are formed by condensation of aldehydes or ketones with primary amines, but they form with more difficulty than enamines.84,85 A special case of enamine preparation was described with 20-oxo-steroids.86 Treatment of these ketones with a primary amine gives a 20-ketimine, which is acetylated with acetic anhydride, with migration of the double bond and formation of 20-(A-acetylalkylamino)-J17(20)-pregnene (14) reduction of 14 with lithium aluminum hydride affords the enamine. 

Heterocycle (427) gives naphthyridone (128) (69% yield) in a Vilsmeier reaction <83IJC(B)916>. Compound (428) and alkyne (429) yield product (430) (75% yield) in acetonitrile at 110°C and product (431) (58% yield) in toluene at 110°C <87CB1427>. Maleic anhydride reacts with enamine (432 R1 = Me, Et R2 = H, Me) giving pyranopyridtriones (433) (9-27% yield) <80S698>, and a mechanism has been proposed for this transformation. 

Tricyclic compounds of type 205 were produced in about 50% yield from the reactions of isatoic anhydride with lactams " and lactim ethers. ° When A -methylisatoic anhydride was applied instead of isatoic anhydride, the products were the unstable enamines 206, which may undergo further transformations depending on the reaction conditions. - - ... 

Nucleophilic substitution by halide, cyanide, carbon nucleophiles, such as enamines, and acetate (by reaction with acetic anhydride), with concomitant loss of the oxide function, occur smoothly in all three systems, though the site of introduction of the nucleophile is not always that predicted by analogy with pyridine chemistry (a to the AT-oxide), as illustrated by two of the examples below. 

Methanesulfonyl chloride and methanesulfonic anhydride and other alkanesulfonyl chlorides react with enamines of aldehydes and ketones in the same manner with no... 

Bis(methylthio)pyrimidines 40 have been obtained upon reaction of ketones with triflic anhydride (94MIS59]. Cycloaddition reactions of l,3-diaza-l,3-butadienes with haloketenes have been employed for the synthesis of pyrimidones [94T(50)7579). Reaction of 2-trimethylsilyloxy- and 2-trimethyI-silylthio-l,3-diazabutadienes (41) with enamines derived from aliphatic aldehydes (42) leads regio- and stereoselectiveiy to tetrahydropyri-midin-2(l -ones and thiones (43). This reaction type was also used for preparing quinazolines [94H(37)1109],... 

Trimethylsilylazide attacks citraconic anhydride with regiospecificity and catalytically adds to aldehydes in the presence of ZnCl2-18-crown-6. Silylazides react with vinyl and other alkenylsilanes to give bis(silyl)enamines through the thermal rearrangement of intermediate triazolines. Other azides give silyl-aziridines, which also result when silyl bromoazides, obtained from alkenylsilanes, are reduced with LiAlHi. ... 

Dicarboxylic acid dichlorides with less than seven carbon atoms do not react to give tetraketones similar to 117, but instead undergo an intramolecular acylation (72) to give on hydrolysis the vinylogous acid anhydride (118), e.g., from succinyl chloride and the enamine (113). 

Anhydrides have also been employed (31). The mixed anhydride of acetic and formic acid reacts with the enamine (113) to give a 50% yield of 2-hydroxymethylene cyclohexanone (119). 

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