Malonamides

A purple or rose pink coloration i produced when sodium hydroxide and dilute copper sulphate solution are added to compounds containing two -CONH- groups attached either to one another, or to the same nitrogen atom, or to the same carbon atom. It is therefore also given by oxamide, NHjCO CONH, malonamide, NHtCO-CH, CONH, and by proteins and peptides. In fact the -COKH - is often spoken of as the peptide linkage. 

Compounds such as malonic esters, malonamide and cyanoacetamlde, in which a —CH— or —CHj— group is situated between —COjR, —CN, or —CONH— groups. 

Eluoropyridine derivatives can be constmcted from fluoroaUphatic feedstocks. 5-Eluoro-2,6-dihydroxynicotinamide [655-15-OJ, a precursor to the anti-bacterial, enoxacin [74011-58-8] was prepared in 63% yield from ethyl fluoroacetate [459-72-3] ethyl formate [109-94-4], and malonamide [108-13-4] (394). 

The first reaction can be conducted using various derivatives of methylenemalonic ester, such as malononitriles 7, malonamides 8, P-keto-esters 9 or Meldrum s acid 10. Substitutions of the aryl ring (including fused rings) and within the aryl ring are well tolerated for this reaction. 

Preparation. A continuous process is described in Ref 26 for its prepn from nitric acid and acetylene. Other prepns on both lab and industrial scales are by the action on Tetranitro-methane (TeNMe) of K hydroxide in aq glycerol (Ref 16), aq HOCHjSOaNa, or 30% aq H peroxide (Ref 19a) to give the K salt which is treated with sulfuric acid (Ref 16), syrupy phosphoric acid (Ref 20), or best by passing gaseous HC1 thru a suspension of the K salt in anhyd eth (Ref 19a). It has also been prepd by the action of nitric acid on malonamide,... 

Reaction of 1,3-dicarbonyl compounds with IVJV-dimethylformamide dimethyl acetal followed by malonamide in the presence of sodium hydride gives 5,6-disubstituted 1,2-dihydro-2-oxopyridine-3-carboxamides, whereas reaction of the intermediate enamines with cyanothioacetamide or cyanoacetamide in the presence of piperidine provides 2-thioxopyridine-3-carboxamides and 4,5-disubstituted l,2-dihydro-2-oxopyridine-3-carboxamides, respectively <95S923>. P-Enaminonitriles 14 react with p-ketoesters and alkyl malonates, in the presence of stoichiometric amounts of tin(IV) chloride, to afford 4-aminopyiidines 15 and 4-amino-2-pyridones 16 <95T(51)12277>. 

Fig. 8 Influence of concentration on the rate of absorption from the in situ rat intestine. The linear dependence of absorption rate on concentration suggests an apparent first-order absorption process over the range studied. Absorption rates have been calculated from the data in Ref. 15 and the straight lines are from linear regression of the data. Key (O) erythritol ( ) urea ( ) malonamide.

Not surprisingly, the diacid 13 and its diamide are waterlogged with 2-4 molecules of HzO from which they are difficult to liberate. Binding experiments in CHC13, a non-competing solvent, revealed that stoichiometric complexes, e.g. 48 were formed with diketopiperazines 40) (Kh 104) and amides such as malonamide. With structures of inadequate hydrogen bonding capacity, such as sarcosine anhydride, com-plexation does not occur. 

Photolysis at 254 nm of phenylbutazone (220) in aqueous solution raised to pH 8 to 9 with sodium hydroxide gave a mixture of ring-opened products. Reisch etal. identified samples of aniline, the malonamides (221) and (222) and the 2-oxohexanamide (225). When the solution was basified with diethylamine, the amino diamide (223) was produced in addition to (222) and (225). In methanol solution the malonamides (221) and (224) were obtained [132]. In an older study by Pawelczyk and Wachowiak, a 20% solution (pH 10.5) of phenylbutazone sodium was kept in a clear glass bottle in diffused daylight for 2 years. 

When diethyl aminomethylenemalonate (9, R1 = R2 = H) was reacted with aqueous ammonia at 100°C in a closed tube, malonamide was obtained. Decomposition of 9 (R1 = R2 = H) also occurred on the action of boiling aqueous barium hydroxide (1892JCS791). 

Spjuth, L. Solvent Extraction Studies with Substituted Malonamides and Oligopyri-dines, Diss. Chalmers Univ. Techn., Gothenburg, 1999. 

Fig. 26. The ten combining possibilities obtained by bonding the halves A-D from Fig. 25 with the malonamide bridge...

C3O2 + 2H2O HOOCCH2COOH Reaction with ammonia gives malonamide ... 

Aluminum foil, Iodine powder. Carbon disulfide, 1,4,6,9-Tetrabromodiamantane, Sodium bisulfite. Hydrochloric acid. Methanol, Acetonitrile, Acetone, Sodium hydroxide. Magnesium sulfate. Potassium permanganate. Toluene Methylene chloride, 2-Bromomethanol, Trioxane, Aluminum chloride. Magnesium sulfate, Nitroform, Acetone, Sodium bicarbonate. Hexane, Silver nitrate. Acetonitrile 1,2-Dichloroethane, HexamethyldisUane, Iodine, Cyclohexane, 1,3-Dioxolane, Nitroform, Methylene chloride, Dimethylformamide, Sodium sulfate. Hydrochloric acid. Magnesium sulfate. Nitric acid. Sulfuric acid Sulfuryl chloride. Acetic anhydride. Nitric acid. Sodium bicarbonate. Sodium sulfate Nitric acid. Sulfuric acid, Malonamide Nitric acid. Sulfuric acid, Cyanoacetic acid Sulfuric acid, Acetasalicyclic acid. Potassium nitrate Nitroform, Diethyl ether, 1-Bromo-l-nitroethane, Sodium sulfuate... 

Nitric acid. Sulfuric acid, Cyanoacetic acid Sulfuryl chloride. Acetic anhydride. Nitric acid. Sodium bicarbonate. Sodium sulfate Nitric acid. Sulfuric acid, Malonamide Nitroform, Diethyl ether, 1-Bromo-l-nitroethane, Sodium sulfate... 

TNM Nitric acid. Sulfuric acid, Malonamide Secondary high explosive... 

Numerous pyridines have been synthesized using cyanoacetamide (or cyanothioacetamide), malononitrile, malonamide and closely related compounds, which provide the N-C(2)-C(3) fragment for reviews see (86H(24)2023,87H(26)205,93CR1991). Principal co-reagents are a,(3-unsaturated ketones, arylidene malononitriles (review (83H(20)519)), and (3-diketones or (3-ketoaldehydes. 

Cyclization of malonamides (223) by treatment with phosphoryl chloride in boiling 1,2-dichloroethane gave l-(disubstituted amino)-3//-pyrim-ido[l,2-a]quinoline-3-ones (224) (95MI1). 

The malonamide (L) complex [CdChL -MeOH has been prepared in which the coordination about the metal is octahedral, with the malonamide acting as a bidentate N2 donor and the chlorine atoms mutually cis.357 This compound differs from the related, but five-coordinate, zinc complexes which have also been described.358,359 The complexes [Cd(tmu)X2] (X = Cl, Br or I) have been reported and, like the zinc complexes, the ligand has been shown to be coordinated through oxygen.360... 

Malonamid-ale 4-Fluoro-a-[(hydro-xymeihylamino)-benzyliden]-E15/1.682 (aus dcm 4.5-H, — 1,2-oxazol/hr)... 

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