Lactam acetals

With lactam acetals (98), cyclic imidic chlorides (99) (X = Cl), lactim ethers (99) (X = OMe), or certain iminium salts (100) amidoximes form 5-(aminoalkyl) substituted oxadiazoles (Scheme 37)... 

Isocyanides have also been used to prepare unsaturated 5(4//)-oxazolones and they are particularly useful for the synthesis of 4-(aminomethylene)-5(4//)-oxazo-lones 374. For instance, cyclization of an unsaturated isocyanide obtained from condensation of alkyl isocyanoacetates and lactam acetals has been reported (Scheme 7.120). ° ... 

The bicyclic lactam acetal (40) was formed when pyrido[2,l-b][l,3]-oxazinium perchlorate (38) was treated with sodium methylate [70JCS(CC)900]. Treatment of 38 with sodium alcoholate and then with an alkyl halide gave quaternary salts 35, presumably as a mixtures of two stereoisomers (79TL809). 

Amide and lactam acetals in synthesis of heterocyclic compounds 92KGS762. 

A study of ketene A, O-acetals has shown that such compounds derived from lactam acetals may be used in the preparation of larger heterocyclic systems via reaction with a 1,3-dipolar species, the initial cycloadducts stabilizing their structures by aromatization. Pyrrolo[2,3-i/]-l,2,3-triazole derivatives, however, do not undergo such elimination reactions and stable cycloadducts may be obtained. Thus, the lactam acetals (133) give the ketene A,0-acetals (134), which on reaction with p-nitrophenyl azide yield substituted pyrrolo[2,3-d]-l,2,3-triazole derivatives (135) <86CB359l>. 

Diels-Alder cycloaddition reactions with tetrazines provide a useful approach to the preparation of pyrrolo[2,3-d]pyridazines. Thus, the lactam acetal (97), which is in equilibrium with the cyclic ketene A,O-acetal (98), reacts with tetrazines (99) to give the partially reduced product (100) <86CB3600>. The methylthio analogue of the acetal (97) also reacts similarly with tetrazines (Scheme 7) <87JHC545>. 

There are few references to dioxinopyrroles which are compounds which do lend themselves to systematic study. The lactam acetal of 1-methylpyrrole (288) reacts with aldehydes in anhydrous ether (or in the absence of solvent) at room temperature to give the tetrahydro-l,3-dioxino[4,5-6]pyrroles (289) (Scheme 21). These lose one molecule of aldehyde when treated with alcoholic potassium hydroxide to yield the benzhydrols (290) <83IJC(B)1079>. 

Scheme 105. When the reaction was performed with the lactam acetal, 2,2-dimethoxytetrahydroazepine, the product obtained was 1-methylisatin444,445.

Enaminones were obtained from lactam acetals by reaction with active methylene compounds610. Heterocyclic / -enaminoesters are synthons in the preparation of condensed systems611. Acylated alkyl aminoisobutyrylmalonates (145) can be converted to 3-oxo-2-pyrrolines (146)612,613. 

Finally, it should be noted that the investigations of Bredereck60,129 and Meerwein et al.130,131 on the preparation of lactam acetals have significantly widened the scope of utility of O-alkyl derivatives of lactams, and have extended some of the reactions of lactim ethers, discussed in this review, to N-substituted lactam acetals. 

Strong Lewis acids abstract alkoxide groups from amide acetals or lactam acetals to give the corresponding iminium salts, e.g. (96 Scheme 10). Alkoxide transfer from amide acetals to less stable carb-enium ions is also a route from amide acetals to iminium compounds (97). 

A(./V-Disubstituted chloromethyleneiminium chlorides (compare Section 2.1.2.2) react with alcoholic alkoxides at temperatures below 0 C to give amide acetals (433 Scheme 79, yields 30-70%)7" 9,24,28,30,32,35 gy the same method lactam acetals (435) are accessible. From dimethylformamide chloride and catechols the amide acetals (434) were prepared. - The bicyclic amide acetals (436) have been obtained from phenols, formamide and POCb. ... 

The reaction of chlorodiphenoxymethane with dimethylamine yields the amide acetal (459 equation 214). Dialkoxymethyl groups can be transferred by means of dialkoxyalkyltriethylammonium tetraflu-oroborate (460 equation 215) to primary amines and amides, amidines, secondary amines and amides once or twice to give amide acetals (461) and (462) Azodiazoles, e.g. (463) and (464) (Scheme 85), add to ketene dimethylacetal to give lactam acetals. ... 

Photodecomposition of the diazo group containing acetals (472 Scheme 87) furnishes lactam acetals (473) similar compounds are accessible from ketenes and azidoformates. From 1,3-dioxolanes and azidoformate the aminodioxolanes (474) were prepared. " ... 

A special modification of this heterocyclization is the treatment of pyrimidinenamino esters (151) with lactam acetals such as 15294 153 is the primary condensation product, and basic ring closure affords the tricycle 154 (Scheme 34). 

Diamino-6-methyl-l,3,5-triazine has been shown to react with aldehydes in the presence of potassium hydroxide or methanesulfonic acid <91CPB3I80>. Equation (13) shows a similar type of reaction in which formamide (or lactam) acetals condense with the active methyl group of a 1,3,5-triazinedione <85LA65>. 

Cyclic ketene 7V,S-aminals (187) with different ring sizes were used by Marcelis and van der Plas to form (188) (Equation (5)) <87JHC545>. Cyclic lactim ethers (189) and donor substituted 2,5-dihydropyrazines (191) react in their tautomeric ketene (9,A -aminal forms (190) and (192) (194) and (193) are accessible as has been shown in a number of examples (Scheme 34) <77AP(310)936, 90AP(323)89>. The sulfur analogue reacts in the same way. Finally, lactam acetals (195) can be used as an in situ source of cyclic ketene 0,A -aminals (196) and form pyridazines (197) on reaction with... 

Keto aldehyde 6 should be easily formed from lactam acetal ester 7, which should be readily available from isoxazolidine 8. The latter can be constructed by a convergent 1,3-dipolar cycloaddition of nitrone 9 with ethyl acrylate. This strategy to spirocyclic lactams is precedented with nitrones derived from A -benzylhydroxylamine [15]. 

Synthesis of enamines from carboxylic acid amides via 1-alkoxyazomethi-nium salts and amide acetals—Gyclic enamines via lactam acetals— Easy reaction of amide acetals with nucleophiles, urea acetals s. 16, 785 Enamines from carboxylic acid amides GHg + OG N < G G N <... 

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