Alkoxymethylenes

A-Amino derivatives, e.g. (71), are converted to the corresponding NH compounds by nitrous acid and give acyl and alkoxymethylene derivatives with the usual reagents. 

Comprehensive work in this field has been done by Slovak authors (98MI1, 95M1359, 96CCC269, 96CCC371, 97CCC99). They prepared 2-substituted (H, Me, Ph) 4-, 5-, 6-, and 7-nitrobenzoxazoles, which were then reduced to amines (not isolated) and subjected to subsequent nucleophilic substitution with activated enol ethers such as alkoxymethylene derivatives of malonic acid esters and nitrile, 3-oxobutanoic acid esters, pentanedione, or cyanoacetic acid esters to yield aminoethylenes 8. 

Several reactions giving rise to hydroxy- and amino-isoxazoles have also been investigated. Thus the reaction of alkoxymethylene-cyanoacetates and hydroxylamine leading to 5-amino- or 5-hydroxy-isoxazoles proved to be rather useful.It is of particular interest that, by changing the reaction conditions, Bauer and Nambury succeeded in obtaining isomeric aminoisoxazolones (24 25 26). It is also possible to prepare isoxazol-3-ones from some /S-ketoesters. ... 

Substituted malondialdehydes form pyrimidines substituted in the 5-position with an alkyl, aryl, halo, or hetero substituent. The pyrimidine is unsubstituted in the 4- and 6-positions. /3-Dialdehyde equivalents are frequently used in these reactions, for example, 3-alkoxy- or 3-aminoacroleins. With aldehydo ketones, the pyrimidine carries a substituent in the 4- or 6-position. The formyl group in the ketone is normally masked as an alkoxymethylene ketone or as an aminomethylene ketone. A commonly used procedure involves the preparation of a dimethylaminomethyl-ene ketone 645 by reaction of a methyl ketone 644 with DMF dimethylacetal and subsequent reaction with an amidine or guanidine to form the target pyrimidine 646 <2003MI237, 2004JHC461>. 

There are few cases in which free /3-aldehydo esters have been condensed successfully with ureas. Commonly, alkoxymethylene esters are used. The initial reaction leads to an acyclic intermediate that may require a separate treatment to induce ring closure. The reaction of a /3-keto ester with urea may be a two-step process in which case acid catalysis can be used in the formation of an acyclic intermediate, with ring closure effected by strong alkali. When the ester component is a lactone or chromone, the product contains a hydroxyalkyl <2000JME3837> or 2-hydroxyphenyl substituent <2004S942>, as shown by the synthesis of the 5-(2-hydroxyethyl)-4-pyrimidinone 657 and the 6-(2-hydroxyphenyl)-pyrimidine 659. 

The use of 4-heteroarylmethylene- and 4-aryhnethylene-5(47/)-oxazolones as dienophiles in the Diels-Alder reaction has been recently reviewed. More recently the reactivity of the exocyclic double bond of 4-(alkoxymethylene)-5(4//)-oxazolones with several dienes has been assessed. Reaction of 4-(methoxymethyl-ene)-2-phenyl-5(477)-oxazolone and 1,3-butadiene requires the presence of Et2AlCl as a catalyst and even then the Diels-Alder cycloadduct is obtained in low yield. 

Catalytic reduction followed by condensation with alkoxymethylene derivatives 175 afforded 176. Compound 176i was cyclized to 7-ethoxycarbonyl-6,9-dihydro-6-oxo-2-methyl-2//-triazolo[4,5- ]quinoline 177. The IR spectra of compounds 176 revealed CN group stretching vibrations at 2200 cm and NH stretching bands at 2950-3160 and 3445 cm. The UV spectra of 176 showed absorption bands at 280 and 290nm - very similar to those previously reported for 2-methylbenzotriazole. 

The reaction of halogenotriphenylphosphonium halides (triphenyl-phosphine dihalides) with alcohols is a useful method for the synthesis of alkyl halides (see Section II,2b p. 239). It has been found88 that (alkoxymethylene)dimethyliminium halides are formed in the reactions of these reagents with alcohols in N,N-dimethylformamide a possible mechanism is shown. Hydrolysis of the (alkoxymethylene)-dimethyliminium halide intermediate affords a formic ester, whereas... 

X2M(TV21-TV22-alkoxymethylene-TPP) are the only examples of TV,TV -dialkylporphyrin complexes (Scheme 39).16 TV-Aminoporphyrins are stable enough to be metallated only as their amide forms (Scheme 40).158 The X-ray structure analysis of Ni(TV-NTs-TPP) revealed that the Ni ion is coordinated with the macrocycle through three pyrrolic nitrogens and an amide nitrogen. A porphyrin TV-oxide, (7V-0)H2(0EP), and its Cu complex have been reported, but the complex appears to be unstable in solution (Scheme 41),159... 

The widely used synthetic method for the preparation of the title compounds involves the condensation of 2-aminopyridines with 1,3-bifunctional compounds (34) (/i-oxo esters, malonates, or 2-alkoxymethylene malonates)... 

Allopurinol, 1,5-dihydro-4//-pyrazolo[3,4-d]pyrimidin-4-one (53), was first synthesized by Robins <56JA784> and by Schmidt <58HCA1052) from 5-aminopyrazole-4-carboxylic acid derivatives. Several syntheses starting from a simple acyclic intermediate have been reported. Thus, reacting ethyl alkoxymethylene cyanoacetate with hydrazine and formamide at 14(M80°C gave allopurinol in high yield. An acid catalyst lowers the temperature required for cyclization of the intermediate 4-alkoxycarbonyl-3-aminopyrazole and raises the purity and the yield of allopurinol <69BRPI 284084). 

Thiophosphorsaure-amid-0,S-diester setzen sich mit Orthoameisensaure-trialkylestern in Gegenwart von Katalysatoren (z.B. p-Toluolsulfonsaure)807 bzw. Dimethoxy-dime-thylamino-methan in Verdunnungsmitteln (z.B. Ethanol)808 zu Thiophosphorsaure-(alkoxymethylen-amid)- (63—81%) bzw. -(aminomethylen-amid)-0,S-di-estern (64-96%) um ... 

Prim, und sek. Amine reagieren mit Thiophosphorsaure-(alkoxymethylen-amid)-0,S-diestem glatt unter Bildung der entsprechenden (Alkylaminomethylen-amid)-O,S-diester810,8n ... 

Enaminones react98 with alkoxymethylene compounds derived from 1,3-dicarbonyl derivatives according to Bottorf and coworkers99 to give substituted pyridines as a result of Michael addition of the enaminone nitrogen (equation 68). Similarly, nitroolefines can be condensed with enaminone derivatives to give 3-nitropyridine derivatives100 (equation 69). 

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