Amide in acid

Therefore, it is important to use an excess of water so as to shift the equilibria to the products. In contrast to esters, the hydrolysis of an amide in acid does result in the formation of an... 

In acid solution, the free amino acid will be protonated, with a positive charge, and probably soluble in water as are other organic ions. The acylated amino acid, however, is not basic since the nitrogen is present as an amide. In acid solution, the acylated amino acid is neutral and not soluble in water. Water extraction or ion-exchange chromatography (Figure 24-11) would be practical techniques to separate these compounds. 

Therefore, it is important to use an excess of water so as to shift the equilibria to the products. In contrast to esters, the hydrolysis of an amide in acid does result in the formation of an ion (Following fig.). The leaving group here is an amine and since amines are basic, they will react with the acid to form a water soluble aminum ion. This is an irreversible step that pulls the equilibrium through to the products. 

Mn02 - X are generally active cattilysts for oxidation reactions and also active electrode materials for dry cells. Probably due to the high oxidation activity, very few studies have been reported for acid-base properties and catalysis of Mn oxides. Mn02 has been claimed to be efficient for the hydration of nitriles to amides, in which the acidic character of the catalyst seems to play some role. In the case of hydration of acrylonitrile in aqueous solution, a relationship between the equi acid-base point (EABP) of met ll oxides and catalytic function has been suggested. Mn02 (EABP = 3,7) was active and selective for the formation of amide in acidic solution, and MnO (EABP = 11.2) was active in basic solution, but caused more hydration of the C = C bond. 

Oxamide differs from most aliphatic acid amides in being almost insoluble in water, and therefore can be readily prepared from the diethyl ester by Method 2(a). Place a mixture of 5 ml. of concentrated [d o-88o) ammonia solution and 5 ml. of water in a 25 ml. conical flask, for which a welTfitting cork is available. (The large excess of... 

Sodium and potassium hydroxides. The use of these efficient reagents is generally confined to the drying of amines (soda lime, barium oxide and quicklime may also be employed) potassium hydroxide is somewhat superior to the sodium compound. Much of the water may be first removed by shaking with a concentrated solution of the alkali hydroxide. They react with many organic compounds (e.g., acids, phenols, esters and amides) in the presence of water, and are also soluble in certain organic liquids so that their use as desiccants is very limited... 

The melting points of a few selected primary aromatic amides (together with those of the xanthylamides, where known) are collected in Table IV,191. A more detailed list will be found in the column headed Amides in Table IV,175 (Armnalic Carboxylic Acids). 

Hydrolysis may be effected with 10-20 per cent, sodium hydroxide solution (see p-Tolunitrile and Benzonitrile in Section IV,66) or with 10 per cent, methyl alcoholic sodium hydroxide. For diflScult cases, e.g., a.-Naphthoniirile (Section IV,163), a mixture of 50 per cent, sulphuric acid and glacial acetic acid may be used. In alkahne hydrolysis the boiling is continued until no more ammonia is evolved. In acid hydro-lysis 2-3 hours boiling is usually sufficient the reaction product is poured into water, and the organic acid is separated from any unchanged nitrile or from amide by means of sodium carbonate solution. The resulting acid is identified as detailed in Section IV,175. 

Inspired by the many hydrolytically-active metallo enzymes encountered in nature, extensive studies have been performed on so-called metallo micelles. These investigations usually focus on mixed micelles of a common surfactant together with a special chelating surfactant that exhibits a high affinity for transition-metal ions. These aggregates can have remarkable catalytic effects on the hydrolysis of activated carboxylic acid esters, phosphate esters and amides. In these reactions the exact role of the metal ion is not clear and may vary from one system to another. However, there are strong indications that the major function of the metal ion is the coordination of hydroxide anion in the Stem region of the micelle where it is in the proximity of the micelle-bound substrate. The first report of catalysis of a hydrolysis reaction by me tall omi cell es stems from 1978. In the years that... 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

With arylthioamides except for some nitrothiobenzamides (101), yields are usually higher than those obtained above, due to the increased stability of these amides under acidic conditions (3), Rj = Ph, yield 70 to 82% (264, 285, 336, 483, 578, 641). In this case, cyclizations are carried out several hours to reflux, in absolute alcohol, in the presence of melted sodium acetate and few drops of piperidine. 

Aromatic thioamides can be prepared as described in the literature by different ways, either by S -> O exchange between the corresponding benzamides and phosphorus pentasulfide in pyridine solution in the presence of triethylamine (65, 646) as strong base, or by action of H2S on the appropriate nitrile with pyridine and triethylamine solvents using the method of Fairfull et al. (34, 374, 503). In this reaction, thioacetamide in acidic medium can also be used as a H2S generator with dimethylform-amide as the solvent (485). 

FIGURE 20 7 The mecha nism of amide hydrolysis in acid solution Steps 1 through 3 show the for mation of the tetrahedral intermediate Dissociation of the tetrahedral inter mediate is shown in steps 4 through 6... 

In base the tetrahedral intermediate is formed m a manner analogous to that pro posed for ester saponification Steps 1 and 2 m Figure 20 8 show the formation of the tetrahedral intermediate m the basic hydrolysis of amides In step 3 the basic ammo group of the tetrahedral intermediate abstracts a proton from water and m step 4 the derived ammonium ion dissociates Conversion of the carboxylic acid to its corresponding carboxylate anion m step 5 completes the process and renders the overall reaction irreversible... 

The amide group is readily hydrolyzed to acrylic acid, and this reaction is kinetically faster in base than in acid solutions (5,32,33). However, hydrolysis of N-alkyl derivatives proceeds at slower rates. The presence of an electron-with-drawing group on nitrogen not only facilitates hydrolysis but also affects the polymerization behavior of these derivatives (34,35). With concentrated sulfuric acid, acrylamide forms acrylamide sulfate salt, the intermediate of the former sulfuric acid process for producing acrylamide commercially. Further reaction of the salt with alcohols produces acrylate esters (5). In strongly alkaline anhydrous solutions a potassium salt can be formed by reaction with potassium / /-butoxide in tert-huty alcohol at room temperature (36). 

Amides in general are stable to elevated processing temperatures, ak oxidation, and dilute acids and bases. StabiUty is reduced in amides containing unsaturated alkyl chains unsaturation offers reactive sites for many reactions. 

A/-Chloro fatty acid amides have been synthesized from the direct halogenation of the amide in boiling water (28). They are useful as reactive intermediates for further synthesis. Fluorination has also been reported by treating the fatty amide with fluorine-containing acid reagents at 200 °C to reach a fluorinated amide with less reactivity toward fluorocarbon polymers (29). 

Nitrile Process. Fatty nitriles are readily prepared via batch, Hquid-phase, or continuous gas-phase processes from fatty acids and ammonia. Nitrile formation is carried out at an elevated temperature (usually >250° C) with catalyst. An ammonia soap which initially forms, readily dehydrates at temperatures above 150°C to form an amide. In the presence of catalyst, zinc (ZnO) for batch and bauxite for continuous processes, and temperatures >250° C, dehydration of the amide occurs to produce nitrile. Removal of water drives the reaction to completion. 

Acylation. Aromatic amines react with acids, acid chlorides, anhydrides, and esters to form amides. In general, acid chlorides give the best yield of the pure product. The reaction with acetic, propionic, butanoic, or benzoic acid can be catalyzed with phosphoms oxychloride or trichloride. 

MDA reacts with acid anhydrides to form amides. In the reaction with maleic anhydride both of the amino hydrogens are replaced to form the imide, A[,Ar-(methylenedi-/)-phenylene) dimaleimide [1367-54-5]... 

Carboxylic Acid Group. Sorbic acid undergoes the normal acid reactions forming salts, esters, amides, and acid chlorides. Industrially, the most important compound is the potassium salt because of stabiUty and high water solubiUty. Sodium sorbate [7757-81-5] (E,E form [42788-83-0]) is less stable and not commercially available. The calcium salt [7492-55-9] which has limited solubiUty, has use in packaging (qv) materials. 

Introduction of the cobalt atom into the corrin ring is preceeded by conversion of hydrogenobyrinic acid to the diamide (34). The resultant cobalt(II) complex (35) is reduced to the cobalt(I) complex (36) prior to adenosylation to adenosylcobyrinic acid i7,i -diamide (37). Four of the six remaining carboxyhc acids are converted to primary amides (adenosylcobyric acid) (38) and the other amidated with (R)-l-amino-2-propanol to provide adenosylcobinamide (39). Completion of the nucleotide loop involves conversion to the monophosphate followed by reaction with guanosyl triphosphate to give diphosphate (40). Reaction with a-ribazole 5 -phosphate, derived biosyntheticaHy in several steps from riboflavin, and dephosphorylation completes the synthesis. 

PolybenZimidaZoles. The polyben2imida2oles (PBIs) are generally produced by the high temperature, melt polycondensation reaction of aromatic bis-ortho-diamines and aromatic dicarboxylates (acids, esters, or amides) in a reaction such as that shown in equation 11 to form ben2imida2ole [51-17-2] as the repeating unit. 

Hydrolysis of Nitriles. The chemical hydrolysis of nitriles to acids takes place only under strong acidic or basic conditions and may be accompanied by formation of unwanted and sometimes toxic by-products. Enzymatic hydrolysis of nitriles by nitrile hydratases, nittilases, and amidases is often advantageous since amides or acids can be produced under very mild conditions and in a stereo- or regioselective manner (114,115). 

There are two distinct classes of enzymes that hydrolyze nitriles. Nittilases (EC 3.5.5. /) hydrolyze nittiles directiy to corresponding acids and ammonia without forming the amide. In fact, amides are not substrates for these enzymes. Nittiles also may be first hydrated by nittile hydratases to yield amides which are then converted to carboxyUc acid with amidases. This is a two-enzyme process, in which enantioselectivity is generally exhibited by the amidase, rather than the hydratase. 

Pyridazinecarboxylic acids can also be prepared by hydrolysis of esters, nitriles and amides in the presence of acids or alkali. Another interesting method is partial decarboxylation of... 

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