Oxamides, synthesis

Organic molecules have been used as catalysts from the early age of synthetic chemistry. Indeed, the discovery of the first organocatalytic reaction is attributed to J. von Liebig, who found - accidentally - that dicyan is transformed into oxa-mide in the presence of an aqueous solution of acetaldehyde (Scheme 1.1). Subsequently, this efficient reaction found industrial application by forming the basis of the Degussa oxamide synthesis. 

The direct conversion of alcohols and amines into carbamate esters by oxidative carbonylation is also an attractive process from an industrial point of view, since carbamates are useful intermediates for the production of polyurethanes. Many efforts have, therefore, been devoted to the development of efficient catalysts able to operate under relatively mild conditions. The reaction, when applied to amino alcohols, allows a convenient synthesis of cyclic urethanes. Several transition metal complexes, based on Pd [218— 239], Cu [240-242], Au [243,244], Os [245], Rh [237,238,246,247], Co [248], Mn [249], Ru [224,250-252], Pt [238] are able to promote the process. The formation of ureas, oxamates, or oxamides as byproducts can in some cases lower the selectivity towards carbamates. 

CO.NH.CH2OH mw 148j12, N 18.91% crysts (from 50% acetic acid), mp 204° prepd by condensation of fonnaldehyde (40%) with oxamide, (CONH2)2, in the presence of K COg (Ref 2). Welcher (Ref 3) reported a novel synthesis from (CN)a, paraformaldehyde ... 

In certain bicyclic and polycyclic thiadiazoles the ring can be hydrolytically cleaved to an o-diamine and sulfur dioxide. This process is a reversal of the reaction pathway involved in the synthesis of thiadiazoles from o -diamines and thionyl chloride or iV-sulfinylaniline under anhydrous conditions (see Section 4.26.5.1.1), and is analogous to, but much slower than, the hydrolysis of sulfurdiimides. In contrast to (1), which steam distilled without decomposition, steam distillation of [l,2,5]thiadiazolo[3,4-c][l,2,5]thiadiazole (21) produced only oxamide. Under milder conditions (75 °C, 12 h) a mixture of the diamine (22), oxamide and elemental sulfur was obtained (75JOC2749). Similar hydrolytic instability was observed in thiadiazole rings angularly joined to an anthraquinone (70RCR923) and ben-zofuroxan (78CPB3896). 

Industrial uses of HCN are for synthesis of methyl methacrylate and to form adiponitrile (for adipic acid and nylon) by addition to 1,3-butadiene in the presence of nickel(O) phosphite complexes. Waste HCN is also oxidatively hydrolyzed to give oxamide for use as fertilizer. 

The earliest example of this type of synthesis was probably the Wallach synthesis 70AHC(12)103> in which an A, A/ -disubstituted oxamide underwent ring closure with phosphorus pentachloride. The chloro-containing intermediate which formed was reduced by hydriodic acid to give a 1-substituted imidazole. An adaptation of this reaction to the synthesis of 5-chloro-l-methylimidazole is shown in Scheme 1. 

The earliest method of this type was the old Wallach synthesis, which formed the imidazole ring by cyclization of an MiV -disubstituted oxamide with phosphorus pentachloride the usual product was a 1-substituted 5-chloroimidazole (1) (Scheme 2.1.1) [1-4]. Although initially thought to be rather limited in its application, the method was later extended to cyclization of higher symmetrical and unsymmetrical oxamides, and now provides access to a variety of 5-chloroimidazoles [5-8]. 

Pyrrole-2-c oxamide, lV,iV-dimethyl-conformation, 4, 194 Pyrrole-3-carboxamide, N,iV-dimethyl-conformation, 4, 194 Pyrrolecarboxamides synthesis, 4, 242 Pyrrole-2-carboxamides synthesis, 4, 148, 360 Pyrrolecarboxylhydrazides Curtius degradation, 4, 362 Pyrrole-2-carboxylic acid, l-benzyl-3-hydroxy-ethyl ester... 

Dialkyl oxalates are of great interest as solvents, as C2 building blocks in fine chemicals synthesis and as intermediates in the manufacture of oxamide, which serves as a fertilizer mainly in the cultivation of rice. Hydrogenation of dimethyl oxalate was extensively studied at the beginning of the 1980s, when Ube (Japan) and Union Carbide searched jointly for an alternative route to the base chemical ethylene glycol, independent of natural mineral-oil resources [51, 70, 71]. 

The old Wallach synthesis, which ring closed an A, A -disubstituted oxamide, has been adapted to the synthesis of imidazopyridines. Kinetic and labeling experiments support a mechanism involving a nitrile ylide species in this transformation <93JCS(Pl)675). Chlorination and cyclization of... 

Gabriel synthesis. Following Al-alkylation of the oxamide, selective saponification removes the ethyl ester to afford RNHCOOBn. The N-Boc derivative is similarly transformed. 

Biphenanthridine (138) has been prepared by reductive dimerization of phenanthridine by alkali metals, and its structure confirmed by an independent synthesis via a double Pictet-Gams cyclization of an oxamide, as shown in Scheme 46 (62JOC4171). It has also been prepared by thermolysis... 

Oxidative carbonylation of alcohols in the presence of CO provides an economically viable route to dialkyl carbonates and/or oxalates (Eqs. (8.4) and (8.5)), both of which have important industrial applications. Dialkyl carbonates (e.g., dimethyl carbonate, propylene carbonate) are excellent solvents for a variety of organic substances [14]. Dialkyl oxalates have utility as solvents, C2 building blocks in fine chemicals synthesis, and intermediates in the manufacture of oxamide (as a fertilizer) [15]. Hydrogenation of dialkyl oxalates provides an alternative route to ethylene glycol that is independent of oil-derived resources [15,16]. 

Oxidative carbonylation of amines affords alkylurea469 and oxamide 470 [192]. Substituted ureas were prepared efficiently in the presence of Pdl2 and KI under CO and CO2 pressure (total 60 atm) [193]. Synthesis of 2-oxazolidinone (471) by the carbonylation of 2-aminoethanol was carried out efficiently using a catalytic system of Pdl2-KI [194]. 

Buckwalter DJ, Hudson AG, BMoore R, Long TE (2014) Synthesis and characterization of poly(propylene glycol) polytrioxamide and poly(urea oxamide) segm ted copoljmers. PolymInt63(7) 1184-1191... 

Buckwalter DJ, Zhang MQ, Inglefield DL, Moore RB, Long TE (2013) Synthesis and characterization of siloxane-containing poly(urea oxamide) segmented copolymers. Polymer 54(18) 4849 857... 

E. SYNTHESIS OF UREAS AND OXAMIDES BY CARBONYLATIVE OXIDATION UTILIZING NITROGEN-BASED NUCLEOPHILES... 

The compound [Cu(L389)] is isolated after oxidation of [Cu(L340)] by prolonged heating in dimethylformamide [383], The compound [Ni(L398)] can be isolated as a byproduct from the synthesis of [Ni(L337)] (its composition and structure have b n proved by X-ray diffraction (Eq. 2.192) [376]). It is presumably formed by oxidation of [Ni(L337)j to the oxamide, and subsequent condensation of the latter with an excess of en added to the reaction mixture. 

Block and graft copolymer systems have also invoked interest with studies on poly(m-phenylene-isophthalamide)-fe-ethylene oxide or -h-dimethylsiloxane systems where conditions have been established for (AB) and triblock ABA and BAB synthesis. Poly(m-phenylene-isophthalamide) has been grafted with acrylonitrile following metallation in liquid ammonia. Regular copolyamide sequences have been prepared by a two-stage low-temperature solution polymerization yielding biphenylene terephthalamide-adipamide and dimethyl piperazine terephthalamide-adipamide copolymers. The preparation of regular aliphatic-aromatic copolyoxamides from diamine-oxamides and aromatic diadd... 

The Hantzsch thiazole synthesis from thioamides and a-halogeno-ketones has been applied to iVAr-(dimethyl)dithio-oxamide to give 2-(dimethylthio-carbamoyl)thiazoles, but in some cases it took another course. Thus, 1-alkylthiocarbamoyl-l-cyanoacetophenones (91) react with bromo-ketones with elimination of alkylamine, giving 2-methylidene-l,3-oxathioles (92). The thio-anilide of acetoacetic acid reacts with 2-bromo-l-tetralone to give the spiro-... 

Dibutyl oxalate, which is the starting material for oxahc acid and oxamide (6000 and 600 t/year, respectively) synthesis, is prepared nowadays using such a carbonylation route. 

Jadhav, P. K. Man, H. W. 1996. Synthesis of 7-membered cyclic oxamides Novel HIV-1 Protease Inhibitors. Tetrahedron Lett. 37 1153-1156. 

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