Aliphatic amides

1 Aliphatic Amides The molecular ion peak of straight-chain monoamides is usually discernible. The dominant modes of cleavage depend on the length of the acyl moiety, and on the lengths and number of the alkyl groups attached to the nitrogen atom. 

The base peak in all straight-chain primary amides higher than propionamide results from the familiar McLafferty rearrangement. 

Primary amides give a strong peak at m/z 44 from cleavage of the R—CONH2 bond  

The base peak (mlz 59, H2NC(=OH+)CH2 ) in all straight-chain primary amides higher than propi-onamide results from the familiar McLafferty rearrangement. Branching at the a-carbon (CH3, etc.) gives a homologous peak at m/z 73 or 87.  

By the dehydration of the ammonium salt of the corresponding acid by heat or by distillation, for example  

An excess of acetic acid is usually added before heating in order to repress the hydrolysis (and also the thermal dissociation) of the ammonium acetate, thus preventing the escape of ammonia. The excess of acetic acid, together with the water, is removed by slow fractional distillation. The method is rarely used except for the preparation of acetamide. 

By heating the acid or its ammonium salt with urea  

Acetic acid Urea Acetamide Carbamic Acid 

The reaction commences at about 120° the carbamic acid formed decomposes immediately into carbon dioxide and ammonia. The latter may form the ammonium salt with unreacted acid the ammonium salt also reacts with urea at temperatures above 120° to yield the amide  

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Aliphatic amides may be hydrolysed by boiling with 10 per cent, sodium hydroxide solution to the corresponding acid (as the sodium salt) the alkahne solution should be acidified with dilute sulphuric acid any water-soluble acid may then be distilled from the solution. Alternatively, hydrolysis may be eflfected with 10-20 per cent, sulphuric acid. The resulting ahphatic acid (usually a liquid) may be characterised as detailed in Section 111,85. 

It may be noted that primary aliphatic amides are readily converted by hydro-xylamlne hydrochloride into hydroxamic acids, which may be detected by the addition of ferric chloride solution ... 

Amino-pyridazines and -pyridazinones react with monomethyl- or iV,A-dimethyl-formamide and other aliphatic amides in the presence of phosphorus trichloride, thionyl chloride, phosgene or benzenesuUonyl chloride to give mono- or di-alkylaminomethyl-eneamino derivatives. The same compounds can be prepared conveniently with A,iV-dimethylformamide dimethyl acetal in high yield (Scheme 50). 

When o-aminobenzophenone is heated with formamide in the presence of formic acid at 150°C for 20 min, a quantitative yield of 4-phenylquinazoline is obtained. In the absence of formic acid longer heating is necessary. Although this reaction does not proceed with o-acylamidobenzophenones, its extension to other o-acylanilines with aliphatic amides may prove fruitful. 

Hydroxyquinazolines are most conveniently obtained by the Niementow ski reaction whereby an anthranilic acid is fused with an aliphatic amide. This reaction has been used extensively and the yields are generally over... 

Cefmetazole (78) is a cephamycin-inspired cephalosporin differing from the mainstream compounds in having an aliphatic amide moiety attached to C-7. Its antibacterial spectrum is similar to the second generation agent cefoxitin. The synthesis starts with 7-aminocephalosporan-... 

The amide group of polyacrylamide offers a reactive site to change the ionic character or to cross-link the polymer. A polyacrylamide solution undergoes general reactions of the aliphatic amide group [1,2,11]. The impor-... 

The student should carry out the following simple experiments with acetamide or with any other aliphatic amide, e.g., n-caproamide they illustrate some of the general reactions of primary aliphatic amides. 

In addition, a fluid loss additive for oil-based drilling fluids, which consists of fatty acid compounds and lignite or humic acid, an oil-soluble or oil-dispersible amine or amine salt with phosphorie acid, or an aliphatic amide or hydroxyamide [392], has been described. 

Chloro- and sulfonamide-substituted aromatic amides showed decreased binding affinity and in vivo potency compared to the simple aliphatic amides. Side chains with an additional (CH2)i-2 linker between the amide and the phenylsulfonamide group resulted in partial or absent in vivo effects [113]. The (CH2)-linked compound, (153), showed around 80-fold selectivity for CB2 over CBi binding [107]. 

Aliphatic amides possess more strong a-C—H bonds in comparison with amines. This is the result of the carbonyl group influence on the stabilization of the formed a-amidoalkyl radical formed from amide in the reaction with the peroxyl radical. This influence is not so strong as that of the amine group. The values of the a-C—H bond in a few amides were estimated recently by the IPM method [4] and are given here. 

While ester, carbonate, carbamate and anilide hydrolyses have been catalysed effectively by antibodies, the difficult tasks of hydrolysis of an aliphatic amide or a urea remain largely unsolved. Much of this problem hinges on the fact that breakdown of a TF is the rate-determining step, as established by much... 

Mono-A-alkylation of the amides occurs under relatively mild liquiddiquid two-phase conditions (Table 5.10), using concentrated aqueous sodium or potassium hydroxide. Under soliddiquid conditions with sodium hydroxide-potassium carbonate or potassium hydroxide, or by using super-saturated aqueous potassium or sodium hydroxide, it is possible to control the reaction to obtain either the mono-or dialkylated derivatives f2-4]. Soliddiquid two-phase conditions also provide the most effective route to mono-AI-alkylalion of weakly acidic aliphatic amides, but it has been suggested that the procedure is not sufficiently selective for the monoalkylation of the more acidic amides [4],... 

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