Malonic acid diamide

Barbituric acid can be considered as a cyclized malonic acid diamide (malonyl-urea). It is therefore a cyclic diketone that may be classified, in the sense of the compounds discussed in Section 12.6, as a coupling component with a methylene group activated by two carbonyl groups in the a- and a -positions. The reaction with arenediazonium salts was studied by Nesynov and Besprozvannaya (1971). These authors obtained coupling products (in good yield) that they considered to be arylhydrazones. Coupling with 4-(phenylazo)benzenediazonium chloride was studied by Chandra and Thosh (1991). The lH NMR spectra of these compounds are consistent with the arylhydrazone structure 12.68. 

Nitrition of ketones 313 and malonic acid diamide 312 also leads to the formation of furoxans 314 (Scheme 78) C1999CHE1415, 2004T1671, 2005MRC563>. 

Malonic acid diamide, m4 Malonylurea, bl Margaryl alcohol, hi a Mellitic acid, b20 MEM chloride, m74 Menadione, m321 1,8-Mentanediamine, d51 / -Mentha-1,8-diene, L17, L18 / -Mentha-6,8-dien-2-one, c20 Mercaptobenzene, tl 56... 

NHC(0)R 149). Malonic acid reacts with SF5NCO at BO C to give both the amide acid, SF5NHC(0)CH2C00H, and the diamide, SFsNHC(O)-CH2C(0)NHSF5 149). This diamide is also obtained from the reaction of SF5NH2 with carbon suboxide 149). 

The barbiturate series of hypnotics are easily and cheaply made from phosgene [577]. Typically, a dialkyl malonic ester is treated with strong aqueous ammonia to give the diamide of the substituted malonic acid. Equation (4.14). This substance is then heated in an autoclave with phosgene for several hours at about 100 C to give the corresponding dialkyl barbituric acid [577]. 

The diamides of malonic acid (124) confirm the 1-2 ring opening and were also detected among the degradation products.305,308,312-315 Compounds... 

Trochimczuk A.W. Chelating resins with N-substituted diamides of malonic acid as ligands. European Polymer Journal 1998 341657-1662. 

Method One, Willstatter (862-864). Diethyl sodium malonate + trimetbylene bromide - diethyi y-bromopropylmalonate diethyl bromo-y-bromopropylmalonate -> diethyl amino-Y-anunopropylmalo-nate a,a-pyrrolidinedioarbonic acid diamide proline. 

The pyrido[l,2-a]pyrimidines (63) were obtained by Shur and Israelstam by reacting 2-aminopyridines and diethyl malonate in polyphosphoric acid at 160-170°C. 2-Aminopyridine and diethyl malonate at 13(TC gave the diamide (65 R = H), which could then be cyclized in polyphosphoric acid at 160 C to pyrido[l,2-ci]pyrimidine (63 R = H). From 2-amino-6-methyl-pyridine and 2-amino-5-halopyridines at temperatures up to 170°C, only the diamides (66) were isolated.41... 

The chemistry of selenazoles is reviewed in a book <04MI777>. Addition of malonic dinitrile with phosphorus pentaselenide in aqueous ethanol affords selenomalonic diamide 282, which undergoes double cyclization with phenacyl bromide to furnish bis(selenazole) 283 <04S875>. 2-Acyl-l,3-selenazoles 287 are prepared in two steps from bromomethyl ketones 284 and selenoamides 285. A facile preparation of l,3-selenazole-5-carboxylic acids 289 is based on the cyclization of selenazadienes 288 with chloroacetyl chloride <048233>. 

Sugai and coworkers [30] have studied the substrate specificity and enantio-selectivity of NHase and amidase from R. rhodochrous IFO 15564 by applying a series of a,a-disubstituted malononitriles, which the NHase converted into the corresponding malonic diamides. Subsequently, the amidase preferentially hydrolyzed the pro-(R) amide in an enantiotopic group-selective manner. The introduction of a fluorine atom at the a-position caused an inhibitory effect on the amidase. A direct application of this route led to the synthesis of ( )-a-cyano- -fluoro-a-phenylacetic acid (CFPA). 

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