Oxalic amides

Scanlan, E.M., Slawin, A.M.Z., and Walton, J.C. (2004) Preparation of [5- and y-lactams from cabamoyl radicals derived form oxime oxalate amides. Organic e[ Biomolecular Chemistry, 2, 716-724. 

Fig. 95 Oxalic amides in silver-catalyzed Minisci reactions...

An efficient use of triphosgene, as an acid activator, for the synthesis of substituted 2-azetidinones via ketene-imine cycloaddition reaction using various acids and imines has been achieved <02T2215>. Novel routes to monocyclic (3-lactams 13 and 14 through the photochemical decomposition of oxime oxalate amides <02CC2086> and a-oxoamides <02OL1443> have also been described. 

Nguyen et al. have recently examined the structure-directing properties of the hydroxyl group, which would appear to be a useful supramolecular functionality capable of forming strong, predictable O-H O networks such as that illustrated in synthon IV [34]. The structures of a number of new urea and oxal-amide derivatives (8-10) were found, however, to exhibit considerable variation... 

Scheme 17 Oxime oxalate amides as fS-lactam precursors...

Attempts were also made to access penicillin derivatives by this route. Several thiazolidine-containing oxime oxalate amides were prepared and photol-ysed under the same conditions, but without success [84]. It is known that and other conventional cyclisations onto oxime ether acceptors (> C = NOR) are faster than onto alkene acceptors [85]. In the hope that cyclisation onto an oxime ether acceptor would also be more efficient, oxime oxalate amide 80 containing both a thiazolidine ring and oxime ether acceptor was prepared. The photosensitised reaction of 80 did yield the desired carbamoyl radical 81, as shown by EPR spectroscopy. However, the presence of the thiazolidine ring evidently inhibited 4-exo cyclisation because no significant amount of cyclisation to radical 82 took place and none of the penicillin derivative was isolated. 

Scanlan and Walton have described the synthesis of a series of oxime oxalate amides (147). These undergo methoxyacetophenone-sensitized irradiation to afford the radicals (148) formed by CC bond fission and loss of CO2. The radicals can undergo cyclization to afford lactams. Thus, for example, the derivative (147e) cyclizes to yield the radical (149) that is oxidatively converted to the final product (150) obtained in 70% yield. 

Amide oxalic amide-iutrile. QHgON . -MW, 70. M.p. 60°. Sol. HgO, EtOH, EtgO. Heat —> HCN -I- cyanurio add. Cone. HQ—> oxamide. 

One has to take into account the possibility that the oxalic amide derivatives of the type (83) can form micelles, as they contain both hydrophilic and hydrophobic structures. 

Ethyl oxalate is the only liquid ester which gives this rapid separation of the amide, which is therefore characteristic. Methyl and ethyl formate react rapidly with ammonia, but the soluble formamide does not separate methyl succinate gives crystalline succinamide after about I hour s standing, other esters only after a much longer time. The solid esters, other than methyl oxalate, are either soluble in water and remain so when treated with ammonia, or alternatively are insoluble in water and hence clearly not methyl oxalate. 

Of the common esters, methyl oxalate (solid, m.p. 54°) and ethyl oxalate (liquid) give amides almost immediately upon shaking with concentrated ammonia solution. The resulting oxamide, m.p. 417°, is valueless as a derivative. The esters may, however, be easily hydrolysed and identified as above. 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

The treatment of kasuganobiosamine with dimethyl ester of oxalic acid followed by concentrated aqueous ammonia gave two kinds of amides. The amide (11a) with pK a 7.6 was identical with the amide of kasugamycinic acid, which was prepared from kasugamycinic acid by treatment with anhydrous hydrogen chloride-methanol followed by concentrated aqueous ammonia. The other isomer (lib) with pK a 7.8, was named amide of isokasugamycinic acid. 

The reaction of cyclooctanone with diethyl oxalate, followed by decarbonylation of the resulting glyoxylate, has been reported to yield 32% of 2-carbethoxycyclooctanone.2 The reaction of cyclooctanone with sodium amide in ether, followed by the... 

Many of these salts melt or sublime before or during decomposition and reaction temperatures generally increase with molar mass. Thermal analyses for a selection of ammonium carboxylates have been given by Erdey et al. [915] who conclude that the base strength of the anion increases with temperature until it reaches that of NH3. Decompositions of ammonium acetate (>333 K) and ammonium oxalate (>473 K) proceed through amide formation. Ammonium benzoate and ammonium salicylate sublime (>373 K) without decomposition but ammonium citrate decomposes (>423 K) to yield some residual carbon. 

Treatment of D-glucoascorbic acid (XV) with diazomethane gives a 2,3-dimethyl derivative (LXXIX) and this upon repeated treatment with silver oxide and methyl iodide yields 2,3,5,6,7-pentamethyl-D-glucoascorbic acid (LXXX). Ozonization of the latter followed by hydrolysis gives oxalic acid and 3,4,5-trimethyI-D-arabonic acid (LXXXI). This acid was shown to possess a free hydroxyl group at C2 by reason of the fact that the amide of LXXXI gives a positive Weerman reaction for a-hydroxy amides, i.e., when the amide is treated with sodium hypochlorite, sodium isocyanate is produced, the latter being identified by... 

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