Diamides, hydrolysis

Investigations of the interaction of the divalent cations of magnesium, calcium, manganese, iron, nickel, copper and zinc with the diacid diamide hydrolysis products of both ICRF 159 and ICRF 192 showed that the metal-binding affinities were similar in all cases with the exception of zinc which was bound less avidly by the hydrolysis product of ICRF 159131). No cytotoxic mechanism for the zinc chelate of the hydrolysis product of ICRF 159 has been established. It is unlikely that the intracellular chelation of zinc is the primary mechanism of cytotoxicity as the hydrolysis product of ICRF 192 binds zinc most avidly. 

Succinic acid reacts with urea in aqeous solution to give a 2 1 compound having mp 141°C (116,117), which has low solubiUty in water. A method for the recovery of succinic acid from the wastes from adipic acid manufacture is based on this reaction (118,119). The monoamide succinamic acid [638-32-4] NH2COCH2CH2COOH, is obtained from ammonia and the anhydride or by partial hydrolysis of succinknide. The diamide succinamide [110-14-3], (CH2C0NH2)2, nip 268—270°C, is obtained from succinyl chloride and ammonia or by partial hydrolysis of succinonitrile. Heating succinknide with a primary amine gives A/-alkylsucckiknides (eq. 9). 

The method of evaluation of the rate constants for this reaction scheme will depend upon the type of analytical information available. This depends in part upon the nature of the reaction, but it also depends upon the contemporary state of analytical chemistry. Up to the middle of the 20th century, titrimetry was a widely applied means of studying reaction kinetics. Titrimetric analysis is not highly sensitive, nor is it very selective, but it is accurate and has the considerable advantage of providing absolute concentrations. When used to study the A —> B — C system in which the same substance is either produced or consumed in each step (e.g., the hydrolysis of a diamide or a diester), titration results yield a quantity F = Cb + 2cc- Swain devised a technique, called the time-ratio method, to evaluate the rate... 

Perfluorosuccinamide-Lithium Aluminum Hydride (Danger of Explosion). In an attempt to reduce perfluorosuccinamide to the corresponding diamine, it was added to an ether soln of lithium aluminum hydride in a nitrogen atm. Hydrolysis was then attempted, but as a second drop of w was added, a violent expln and ether fire resulted. It was shown that the diamide and the lithium aluminum hydride reacted to give an unstable complex which detonated at room temp Ref T.S. Reid G.H. Smith, C EN 29,3042 (1951) CA 46, 3279 (1952)... 

Reactions leading to surface-active diamides form emulsions of the hydrated [A1(H20)6]C13 complex. However, by hydrolysis of the RPOCl2-AlCl3 complex with water at a molecular ratio of 1 6-7.5 in methylene chloride at a temperature of -10°C, the A1C13 from the complex reacts selectively forming a precipitation of [A1(H20)6]C13, which can be easily filtered off. From the solvent the alkanephosphonic acid dichloride can be isolated in good quality (Table 4). 

The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

The compounds are, in general, stable and fairly resistant to hydrolysis in spite of the >POF grouping. We showed, for example, that diphenylphosphorodiamidic fluoride could be recrystallized from aqueous alcohol. Tetramethylphosphoro-diamidic fluoride was not affected to any extent by contact with water at 18° for 6 hr. The reaction between n/2 aqueous sodium hydroxide solution and the compound was studied. The extent of hydrolysis (removal of fluorine) after 30 min. was about 8-9 per cent, and even after 500 hr. it was only 29-9 per cent. The compound is also affected by acid. 

Initially, one molecule of fatty acid reacted with the secondary amine of BETA, followed by a second fatty acid molecule, reacting with one of the two primary amines. The product formed was the N-(2-aminoethyl) diamide, which will be referred to as the diamide. The diamides could be cyclized by heating under vacuum to form imidazolines, which were unstable to hydrolysis. In the presence of water, or upon exposure to atmospheric moisture, they revert back to the diamide. 

Controlled hydrolysis of the cyano groups of 58 can give any one of the three possible products the diacid 85, the amide/acid 87, or the diamide 88 in excellent yields (72GEP2216925). Decarboxylation of 87 to 3,5-diamino-6-carbamoylpyrazine (89), and its subsequent conversion to 3,5-diaminopyra-zinoic acid (90) by hydrolysis has also been demonstrated. 

Attempts to prepare 2,3,5,6-tetraaminopyrazine (91) by Hoffman degradation of the diamide (88) were unsuccessful. This is apparently due to both intermolecular and intramolecular urea formation from the intermediate isocyanate giving a mixture of products, which upon attempted hydrolysis to 91 undergo a significant amount of attack on the pyrazine ring (70UP1). 

Diomides. These compds are the dibasic acid derivs of ammonia or amines, and contain two -CONH2 groups. Numerous combinations of diacids, diamines, and amino acids have been interacted. Copolymers contg various proportions of two or more diacids have been prepd (Ref 2). The diamide of carbonic acid is called urea, H2NCONH2. It is a product of animal metabolism and is prepd industrially by reaction of CO2 with excess NH3 at high temp, or by an older method involving the hydrolysis of cyanamide (Ref 5)... 

HYDROLYSIS OF DIAMIDES, LACTAMS AND N-acyl-ammonium IONS... 

The hydrolysis of diamides has been studied by Bruylants et al.178t258t259, who found that, for complete hydrolysis, the reaction may be looked at as a sequence of two consecutive-competitive reactions, viz. 

KINETIC DATA FOR THE ACID AND BASE HYDROLYSIS OF SOME DIAMIDES... 

Sugo, Y., Sasaki, Y., Tachimori, S. 2002. Studies on hydrolysis and radiolysis of V,lV,lV ,./V -tetraoctyl-3-oxapentane-l,5-diamide. Radiochim. Acta 90 161-165. 

Dinitriles and diamides also can sometimes be partially hydrolyzed by use of enzymes. As with other enzymatic reactions, small structural modifications can substantially modify the suitability of a given substrate. Scheme 10.3 gives illustrative examples of the highly substrate-dependent hydrolysis of dinitriles and diamides by use of a microorganism. 

Scheme 10.3. Microorganism-mediated hydrolysis of dinitriles and diamides [9],...

Thus it appears that the starting methyl ester gg undergoes base-catalyzed cyclization to give the intermediate 12, which is opened by hydroxide attack at phosphorus to give lg. The desired diamide 9, formed either by direct hydrolysis of c or by opening of the intermediate 2 at the carbonyl carbon, loses ammonia with assistance from the free carboxylate to give li-... 

One of the possibilities to convert the amino nitrile (R,S)-3 to (5)-terMeucine (7) is shown in the reaction sequence of Scheme 25.3. Hydrolysis of the aminonitrile (R,S)-3 to the diamide 5 was performed in concentrated sulfuric acid. Removal of the phenylacetamide group using H2 and Pd-C gave (S)-tert-leucine amide (6). Acidic hydrolysis of the amide 6 yielded (S)-tert-leucine (7) in 73% overall yield for the 3 steps and an enantiomeric excess of >98%. The overall yield for this nonoptimized protocol is 66% based on pivaldehyde. Obviously, other routes to convert the amino nitrile to the amino acid can be envisaged. As an example, by heating the diamide in sulfuric acid, after dilution with water, the diacid can be obtained that, after hydrogenolysis, affords the amino acid in 2 steps from the amino nitrile 3. 

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