Amides, substituted

If the amide is an N-(mono- or di)-substituted amide, or the imide an N-substituted imide, the above alkaline hydrolysis will give a solution... 

By treatment of this oxime with phosphorus pentachloride or thionyl fhloride in ether solution, smooth conversion into benzanilide, m.p. 163°, results. The change of any oxime into a substituted amide under the conditions mentioned is usually termed the Beckmann rearrangement. The above example may be represented ... 

This group comprises substances of the tjrpe RCONHR and RCONR R", i.e., substituted amides of the aromatic series. They are all well-defined crystalline sohds, sparingly soluble in cold but, often, appreciably soluble hi hot water and moderately soluble in ether they are generally neutral or feebly basic in reaction. 

It will be observed that the reaction involves two equivalents of the amine and produces, in addition to the substituted amide, an equivalent quantity of the amine hydrochloride. Acetic anhydride, on the other hand, converts the amine quantitatively into the acyl derivative, for example ... 

Hydrolysis of a substituted amide. A. With 10 per cent, sulphuric acid. Reflux 1 g. of the compound (e.g., acetanilide) with 20 ml. of 10 per cent, sulphuric acid for 1-2 hours. Distil the reaction mixture and collect 10 ml. of distillate this will contain any volatile organic acids which may be present. Cool the residue, render it alkaline with 20 per cent, sodium hydroxide solution, cool, and extract with ether. Distil off the ether and examine the ether-soluble residue for an amine. 

Thiazolium salts with alkyl (103, 722), arylalkyl (116), aryl (305), or heteroaryl (96) substituents on the nitrogen have been also prepared by this procedure. As in the thiazole series, N-substituted thioamides can be formed directly in the reaction mixture from phosphorus pentasulfide and N-substituted amides (127). These methods are important in the synthesis of thiamine 102 (vitamin Bj) (Scheme 45). 

Primary amines (RNH2) yield N substituted amides (R CNHR)... 

Adiponitrile undergoes the typical nitrile reactions, eg, hydrolysis to adipamide and adipic acid and alcoholysis to substituted amides and esters. The most important industrial reaction is the catalytic hydrogenation to hexamethylenediarnine. A variety of catalysts are used for this reduction including cobalt—nickel (46), cobalt manganese (47), cobalt boride (48), copper cobalt (49), and iron oxide (50), and Raney nickel (51). An extensive review on the hydrogenation of nitriles has been recendy pubUshed (10). 

Transamidation. Polyacrylamide reacts with primary amines such as hydrazine [302-01-2], N2H4, (54) and hydroxjlamine [7803-49-8]. NH O, (55—57) to form substituted amides with loss of ammonia. 

Amidation. Heating of the diammonium salt or reaction of the dimethyl ester with concentrated ammonium hydroxide gives adipamide [628-94-4] mp 228°C, which is relatively insoluble in cold water. Substituted amides are readily formed when amines are used. The most industrially significant reaction of adipic acid is its reaction with diamines, specifically 1,6-hexanediamine. A water-soluble polymeric salt is formed initially upon mixing solutions of the two materials then hea ting with removal of water produces the polyamide, nylon-6,6. This reaction has been studied extensively, and the hterature contains hundreds of references to it and to polyamide product properties (31). 

Acrylamide—acrylic polymers are made by free-radical polymerization of monomers containing the acryHc stmcture, where R is —H or —CH and is —NH2 or a substituted amide or the alkoxy group of an ester. 

With sodium azide, salts of secondary nitroparaffins rearrange to N-substituted amides (29). With SO2, primary or secondary nitroparaffins give imidodisulfonic acid salts (30). Potassium nitroform reacts quantitatively with nitryl chloride in ether to form tetranitromethane (31). 

Hydrolysis of primary amides cataly2ed by acids or bases is very slow. Even more difficult is the hydrolysis of substituted amides. The dehydration of amides which produces nitriles is of great commercial value (8). Amides can also be reduced to primary and secondary amines using copper chromite catalyst (9) or metallic hydrides (10). The generally unreactive nature of amides makes them attractive for many appHcations where harsh conditions exist, such as high temperature, pressure, and physical shear. 

Substituted Amides. Monosubstituted and disubstituted amides can be synthesized with or without solvents from fatty acids and aLkylamines. Fatty acids, their esters, and acid halides can be converted to substituted amides by reaction with primary or secondary aLkylamines, arylamines, polyamines, or hydroxyaLkylamines (30). Di- -butylamine reacts with oleic acid (2 1 mole ratio) at 200—230°C and 1380 kPa (200 psi) to produce di-A/-butyloleamide. Entrained water with excess -butylamine is separated for recycling later (31). 

Refluxing linoleic acid and a primary or secondary alkyl amine with -toluenesulfonic acid in toluene for 8—18 h also yields the substituted amides (32—34). The reaction of methyl esters with primary or secondary amines to make substituted amides is catalyzed with sodium methoxide. Reactions are rapid at 30°C under anhydrous conditions (35). Acid chlorides can also be used. Ai,A/-dibutyloleamide [5831-80-17 has been prepared from oleoyl chloride and dibutyl amine (36). 

Alkanolamides, a special subclass of substituted amides used as surfactants, are produced by three principal methods the reaction of fatty amides with formaldehyde, fatty acids with hydroxyalkylamines, and fatty esters with hydroxyalkylamines (37). A fatty amide and formalin can be heated in the presence of sodium hydroxide to yield 70—95% substituted alkanolamides (38,39). 

Another subclass of substituted amides that is of great commercial value is the ethoxylated amides. They can be synthesized from alkanolamides by chain extending with ethylene or propylene oxide or by ethoxylation directly from the primary amide (46—48). It was originally beheved that the stepwise addition of ethylene oxide (EO) would produce the monoethano1 amide and then the diethanolamide when sufficient ethylene oxide was added (49), but it has been discovered that only one hydrogen of the amide is substituted with ethylene oxide (50—53). As is typical of most ethylene oxide adducts, a wide distribution of polyethylene oxide chain length is seen as more EO is added. A catalyst is necessary to add ethylene oxide or propylene oxide to a primary or an ethoxylated amide or to ethoxylate a diethoxy alkanolamide synthesized from diethanolamine (54). 

Approximate, 1990. Table 4 Hsts many of the commercially available substituted fatty acid amides. The /V,/V-dimetby1 amides, ethoxylated amides, and other specialty substituted amides are available ia commercial quantities, but are of lower volume. Table 4. Substituted Fatty Acid Amides ... 

Substituted amides CAS Registry Molecular formula Melting range. Flash Gardner color... 

Substituted amides (not of the alkanolamide variety) are sold to diverse low volume markets. They have some utility ki polymers such as polyethylene, ethylene-vinyl acetate copolymers, acryUc polymers, PVC, polyamides, and polyesters. They have been found effective as pharmaceutical processkig aids, defoamers (qv), antimicrobials, pesticides, kisect repellents, dispersion stabilizers, and corrosion inhibitors. 

Inhibition of Nitrosamine Formation. Nitrites can react with secondary amines and A/-substituted amides under the acidic conditions of the stomach to form /V-nitrosamines and A/-nitrosamides. These compounds are collectively called N-nitroso compounds. There is strong circumstantial evidence that in vivo A/-nitroso compounds production contributes to the etiology of cancer of the stomach (135,136), esophagus (136,137), and nasopharynx (136,138). Ascorbic acid consumption is negatively correlated with the incidence of these cancers, due to ascorbic acid inhibition of in vivo A/-nitroso compound formation (139). The concentration of A/-nitroso compounds formed in the stomach depends on the nitrate and nitrite intake. 

Substituted Amide Waxes. The product of fatty acid amidation has unique waxlike properties (13). Probably the most widely produced material is N,1S7-distearylethylenediarnine [110-30-5] which has a melting point of ca 140°C, an acid number of ca 7, and a low melt viscosity. Because of its unusuaHy high melting point and unique functionaHty, it is used in additive quantities to raise the apparent melting point of themoplastic resins and asphalts, as an internal—external lubricant in the compounding of a variety of thermoplastic resins, and as a processing aid for elastomers. 

Ammonolysis or aminolysis of an ester can be used to make the respective amide or N-substituted amide. 

Reaction of cyanohydrins with absolute ethanol in the presence of HCl yields the ethyl esters of a-hydroxy acids (3). A/-substituted amides can be synthesized by heating a cyanohydrin and an amine in water. Thus formaldehyde cyanohydrin and P-hydroxyethylamine lead to A/- (P-hydroxyethyl)hydroxyacetamide (4). 

If primary or secondary amines are used, A/-substituted amides are formed. This reaction is called aminolysis. Hydra2ines yield the corresponding hydra2ides, which can then be treated with nitrous acid to form the a2ides used in the Curtius rearrangement. Hydroxylamines give hydroxamic acids. 

Cyanopyridazines add ammonia, primary and secondary amines and hydroxylamine to give amidines or amidoximes. Substituted amides, thioamides and carboximidates can be also prepared. With hydrazine, 3-pyridazinylcarbohydrazide imide is formed and addition of methylmagnesium iodide with subsequent hydrolysis of the imine affords the corresponding pyridazinyl methyl ketone. 

They are converted by nitrous acid into the organic acid, and in the case of substituted amides into nitrosamides,... 

With the latter class of substituted amides, PCI-, forms the imidochlorides, a reaction hich is usually formulated in two steps,... 

The substituted amides give both imidochloride and the cyanide with PC1-,... 

The carboxyl groups of amino acids undergo all the simple reactions common to this functional group. Reaction with ammonia and primary amines yields unsubstituted and substituted amides, respectively (Figure 4.9a,b). Esters... 

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