Dimethylformamide diethyl acetal

Various other examples in this chapter have already highlighted how N,N-dimeth-ylformamide dimethyl acetal can be efficiently utilized as a synthon for the construction of heterocydic rings (see Schemes 6.189, 6.194, 6.195, 6.229, and 6.230). West-man and coworkers have described a two-step method for the generation of a wide variety of heterocydic scaffolds, based on the initial formation of alkylaminoprope-nones and alkylaminopropenoates from N,N-dimethylformamide diethyl acetal (DMFDEA) and the corresponding CH-acidic carbonyl compounds (Scheme 6.256)... 

In a more recent study, Westman and Lundin have described solid-phase syntheses of aminopropenones and aminopropenoates en route to heterocycles [32], Two different three-step methods for the preparation of these heterocycles were developed. The first method involved the formation of the respective ester from N-pro-tected glycine derivatives and Merrifield resin (Scheme 7.12 a), while the second method involved the use of aqueous methylamine solution for functionalization of the solid support (Scheme 7.12 b). The desired heterocycles were obtained by treatment of the generated polymer-bound benzylamine with the requisite acetophenones under similar conditions to those shown in Scheme 7.12 a, utilizing 5 equivalents of N,N-dimethylformamide diethyl acetal (DMFDEA) as reagent. The final... 

Condensation of aromatic acyl compounds with N,N-dimethylformamide diethyl acetal in a pressure tube under the action of microwave irradiation affords easy access to l-aryl-3-dimethylaminoprop-2-enones in almost quantitative yield after 6 min. These intermediates can then be reacted with hydrazine hydrate under conventional reflux in ethanol to form the corresponding 3-substituted pyrazoles [95] (Scheme 8.69). 

The reaction of diethyl aminomethylenemalonate (13) and N,N-dimethylformamide diethyl acetal in boiling acetic acid gave diethyl N-(dimethylaminomethylene)aminomethylenemalonate (285) in 64% yield (87KFZ1249). 

A, A-Dimethylformamide diethyl acetal serves as an aldehyde equivalent to give 5-dimethylamino-4,5-dihydro-l,2,4-oxadiazoles <86MI 404-04>. Oxadiazoles (171) (R = H) can be methylated or ben-zylated at N(4). With HCl or trichloroacetic acid compounds (171) are protonated on N(2) <73BSF2996>. 

Compound 51 was synthesized by the interaction of the isoquinolinone unsubstituted in position 4 and dimethylformamide diethyl acetal (81KFZ44, 81KGS511). 

Reaction of ethyl ll-cyano-4-oxo-7,8,9,10- tetrahydro-4//-pyrimido[l,2-b]-isoquinoline-3-carboxylate (118 with A,iV-dimethylformamide diethyl acetal in boiling benzene in the presence of aluminum chloride afforded 10-dimethylaminomethylene derivative 119 (84KFZ931). 

N, N-Dimethylformamide diethyl acetal (DMFDEA) is a interesting reagent, since it can be used to form alkylaminopropenones or alkylaminopropenoates when reacted with compounds having activated methylene groups such as (3-ketoesters, acetophenone and N-acylglycine. These alkylaminopropenones or alkylaminopropenoates can subsequently be reacted with dinucleophiles to form a variety of heterocycles. Westman and co-workers32 have used DMFDEA for the synthesis of propenoates and propenones, which were used directly without intermediate purification for the formation of a number of heterocycles in a combinatorial fashion. Some examples are outlined in Scheme 5.16. The reactions were performed in a two-step one-pot procedure, which in this case were more suitable for combinatorial synthesis. 

The reaction of the 9-amino group of 4//-pyrido[l, 2-a]pyrimidin-4-one 602 with N, N-dimethylformamide diethyl acetal in boiling acetone afforded 9-(N,A-dimethylaminomethylene)amine derivative 603 (91H1455). 

Acetophenone and ring-substituted acetophenones condense with dimethylformamide diethyl acetal to give the enaminones 151, which yield 5-arylisoxazoles (152) by reaction with hydroxylamine O-sulphonic acid (equation 66)87. 

Compounds possessing reactive methylene groups condense with dimethylformamide diethyl acetal to give enamines, which may serve as precursors for heterocycles (cf. equations 48 and 66). Thus diethyl 2,6-dimethylpyridine-3,5-dicarboxylate (292) yields the enamine 293, which is converted into isolable secondary (Z)-enamines 294 by the action of primary aromatic amines. Thermal or base-catalysed cyclization then affords the naphthyridones 295 (equation 120)147. 

The reaction of dimethylformamide diethyl acetal with the carbanion which forms when the isocyanide (31) is metalated gives an alkene (32) which reacts with methyl iodide to give an imidazole product (79LA1444). In the presence of base, 2-isocyanoalkane nitriles (33) react with alcohols, thiols or hydrogen sulfide to form imidazoles which have an oxygen or sulfur substituent at C-5 (Scheme 16) (79LA1602). 

When heated with a primary amine hydrochloride in DMF, 4-amino-2-azabutadienes (67), formed by the interaction of dimethylformamide diethyl acetal and an azomethine, cyclize to imidazoles (Scheme 36) (81AG(E)296). Imidazolidin-4-ones are formed when a- (A -acylhydroxyamino) esters react with ammonia (B-77MI40800). 

When 5-nitrosopyrimidine-4,6-diamines are treated with excess dimethylformamide diethyl acetal followed by warming with 10% aqueous ammonia in the presence of ethanol at 80 C for 20 minutes, the corresponding 8-(dimethylamino)adenine derivatives 5 are obtained in almost quantitative yield. ... 

Dimethylchromanes, 317 (2S,6S)-2,6-Dimethylcyclohexanone, 11 Dimethyl diazomethylphosphonates, 157 o,o -Dimethyldibenzylamide, 245 Dimethylformamide diethyl acetal, 157 Dimethylformamide dimethyl acetal, 158 Dimethyl fumarate, 302... 

Amino-2-azabutadienes 1-aminobutadienes. The reaction of dimethylformamide diethyl acetal with azomethines results in 4-amino-2-azabutadienes (1, equation I). 1-Aminobutadienes (2) are obtained by a similar reaction of a,J3- or fi,y-unsaturated esters (equation II). 

N,N-Dimethylforniaiiiide dimethyl acetal. (See N,N-Dimethylformamide diethyl acetal,... 

The aminouracil derivative (259) condenses with dimethylformamide diethyl-acetal to the dimethylaminomethyleneamino compound (260) the thermolysis of which leads to the pyrimido(4,5-b)pyrazine (26/)104 ... 

---