Diamids

Figure 2-31. Sample SOfile for sulfamide (sulfuric diamide).

Urea (the diamide of carbonic acid) can be prepared by the historic method of Wohler. When an aqueous solution of ammonium cyanate is allowed to stand, the cyanate undergoes molecular rearrangement to urea, and an equilibrium mixture containing about 93% of urea is thus formed. Urea is... 

Also known as nitrolim and lime nitrogen. The fresh product contains approximately 55 per cent, of calcium cyanamide, 20 p>er cent, of lime, 12 per cent, of graphite and small amounts of other impurities. It should be protected from moisture when stored in order to prevent slow polymerisation to dicyano-diamide. 

Alternatively, treat a solution of 3 9 g. of the 6is-diazo ketone in 50 ml. of warm dioxan with 15 ml. of 20 per cent, aqueous ammonia and 3 ml. of 10 per cent, aqueous silver nitrate under reflux in a 250 or 500 ml. flask on a water bath. Nitrogen is gently evolved for a few minutes, followed by a violent reaction and the production of a dark brown and opaque mixture. Continue the heating for 30 minutes on the water bath and filter hot the diamide of decane-1 lO dicarboxyhc acid is deposited on cooling. Filter this off and dry the yield is 3 -1 g., m.p. 182-184°, raised to 184-185° after recrystallisation from 25 per cent, aqueous acetic add. Hydrolyse the diamide (1 mol) by refluxing for 2-5 hours with 3N potassium hydroxide (4 mols) acidify and recrystaUise the acid from 20 per cent, acetic acid. The yield of decane-1 10-dicarboxyhc acid, m.p. 127-128°, is almost quantitative. 

Polyfunctional molecules (glycols, dibasic acids, hydroxy acids, diamides, etc.). 

A solution of 0.10 mol of freshly distilled diethylaminopropyne in 80 ml of dry (distilled from phosphorus pentoxide) acetonitrile was cooled to 5°C and dry carbon dioxide was introduced into the vigorously agitated solution at a rate of about 0.3 1/min. The temperature rose above 20°C within a few minutes, but was kept at about 30°C by occasionally immersing the flask in a bath of ice-water. The introduction of CO2 was continued until the temperature had dropped to 25°C and the typical odour of the yneamine had disappeared completely. The yellow solution was concentrated in a water-pump vacuum. The residue, a sirupy liquid, had the theoretically required weight and consisted of reasonably pure (about 955 ) allenyl-diamide. If desired the product car be distilled (short-path distillation) in a high vacuum. It solidified upon standing at -25 C. 

Diamides and triamides have been obtained from the action of an aqueous saturated solution of ammonia on the corresponding ester (Scheme 18) (88). Amides can also be obtained by the Curtius (16) or Hofmann reactions (80). Thus the Curtius reaction with 2-substituted 4-thiazolecarboxylic acids gives the 4-acetamido compounds (16). 

Amides. Names for amides are derived from the names of the acid radicals (or from the names of acids by replacing acid by amide) for example, S02(NH2)2, sulfonyl diamide (or sulfuric diamide) NH2SO3H, sulfamidic acid (or amidosulfuric acid). 

Gc chiral stationary phases can be broadly classified into three categories diamide, cyclodextrin, and metal complex. 

Diamide Chiral Separations. The first chiral stationary phase for gas chromatography was reported by GH-Av and co-workers in 1966 (113) and was based on A/-trifluoroacetyl (A/-TFA) L-isoleucine lauryl ester coated on an inert packing material. It was used to resolve the tritiuoroacetylated derivatives of amino acids. Related chiral selectors used by other workers included -dodecanoyl-L-valine-/-butylamide and... 

Urea can be considered the amide of carbamic acid, NH2COOH, or the diamide of carbonic acid, CO(OH)2. At room temperature, urea is colorless, odorless, and tasteless. Properties are shown ia Tables 1—4. Dissolved ia water, it hydrolyzes very slowly to ammonium carbamate (1) and eventually decomposes to ammonia and carbon dioxide (qv). This reaction is the basis for the use of urea as fertilizer (qv). 

Acryhc esters dimerize to give the 2-methylene glutaric acid esters catalyzed by tertiary organic phosphines (37) or organic phosphorous triamides, phosphonous diamides, or phosphinous amides (38). Yields of 75—80% dimer, together with 15—20% trimer, are obtained. Reaction conditions can be varied to obtain high yields of trimer, tetramer, and other polymers. 

Phosphonomethylated Ethers. A phosphoms-containing ether of ceUulose can be prepared by the reaction of cotton ceUulose with chioromethylphosphonic acid [2565-58-4] ia the presence of sodium hydroxide [1310-73-2] by the pad-dry-cure technique (62). Phosphoms contents of between 0.2 and 4.0% are obtained. This finish is durable but has high ion-exchange properties and is flame resistant only as the ammonium salt. DurabUity on medium weight fabrics is obtained with chi oromethylph osph onic diamide. This finish has never penetrated the flame retardant market (63). 

Derivatives similar to those mentioned for the monofunctional fluorinated carboxyflc acids have been prepared tetrahydrodiols, tetrahydrodiamines, diamides, and diesters. 

Hydrazine [302-01-2] (diamide), N2H4, a colorless liquid having an ammoniacal odor, is the simplest diamine and unique in its class because of the N—N bond. It was first prepared in 1887 by Curtius as the sulfate salt from diazoacetic ester. Thiele (1893) suggested that the oxidation of ammonia (qv) with hypochlorite should yield hydrazine and in 1906 Raschig demonstrated this process, variations of which constitute the chief commercial methods of manufacture in the 1990s. 

Phenformin. Phenformin hydrochloride [834-28-6] (1-phenethylbiguanide, A/-(2-phenylethyl)imidodicarbonimidic diamide), is a white to off-white odorless crystalline power having a bitter taste. The melting point is 175—178°C. It is freely soluble in water and alcohol, and practically insoluble in chloroform, ether, and hexane. Its pH in solution is 6.0—7.0. 

Subsequent chlorination of the amide takes place ia a two-phase reaction mixture (a dispersion of diamide ia hydrochloric acid) through which a chlorine stream is passed. The temperature of this step must be maintained below 10°C to retard the formation of the product resulting from the Hofmann degradation of amides. Reaction of the A/,A/-dichloroamide with diethylamine [109-89-7] ia the presence of base yields /n j -l,4-cyclohexane-bis-l,3-diethylurea (35), which is transformed to the urea hydrochloride and pyroly2ed to yield the diisocyanate (36). 

Amidation. Reaction of maleic anhydride or its isomeric acids with ammonia [7664-41-7] (qv), primary amines (qv), and secondary amines produces mono- or diamides. The monoamide derivative from the reaction of ammonia and maleic anhydride is called maleamic acid [557-24-4] (8). Another monoamide derivative formed from the reaction of aniline [62-53-3] and maleic anhydride is maleanilic acid [555-59-9] (9). 

Oxamide. This diamide [471 6-5] H2NCOCONH2, mol wt 80.07, is sparingly soluble in water and insoluble in various organic solvents. It... 

Its manufacture begins with the formation of dodecanedioic acid produced from the trimeri2ation of butadiene in a process identical to that used in the manufacture of nylon-6,12. The other starting material, 1,12-dodecanediamine, is prepared in a two-step process that first converts the dodecanedioic acid to a diamide, and then continues to dehydrate the diamide to the dinitrile. In the second step, the dinitrile is then hydrogenated to the diamine with hydrogen in the presence of a suitable catalyst. 

Then in a series of chemical transformations the diamine or lactam can be prepared from brassyUc acid (177,178). The diamine is formed as described above for the 12-carbon diamine, ie, diacid —> diamide —> dinitrile —> diamine. The lactam is made from the dinitrile as follows. 

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). 

Complexes of titanium, such as 2,6-(RNCH2)2NC H2TiCl2, prepared by reaction of TiCl with 2,6((CH2)3Si)RNCH2)2NC H2, can react with various Grignard reagents to prepare conformationady rigid diamide mono- and dialkyl titanate complexes (218,219). 

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. 

Carbamic acid is the monoamide of carbonic acid the diamide is the weU-known compound urea [57-13-6] also called carbamide (see Urea). Guanidine [113-00-8] could be regarded as the amidine of carbamic acid (see Cyanamides). 

Ammonium acetate and sodium methoxide are effective catalysts for the ammonolysis of soybean oil (49). Polyfunctional amines and amino alcohols such as ethylenediamine, ethanolamine, and diethanolamine react to give useful intermediates. Ethylenediamine can form either a monoamide or a diamide depending on the mole ratio of reactants. With an equimolar ratio of reactants and a temperature of >250° C, a cyclization reaction occurs to give imidazolines with ethylenediamine (48) ... 

Dicyanoacetylene, 2-hiitynedinitri1e, is obtained from dimethyl acetylenedicarboxylate by ammonolysis to the diamide, which is dehydrated with phosphoms pentoxide (44). It bums in oxygen to give a flame with a temperature of 5260 K, the hottest flame temperature known (45). Alcohols and amines add readily to its acetylenic bond (46). It is a powerhil dienophile in the Diels-Alder reaction it adds to many dienes at room temperature, and at 180°C actually adds 1,4- to benzene to give the bicyclo adduct (7) [18341 -68-9] C QHgN2 (47). 

Organic Acids and Their Derivatives (Anhydrides, Nitriles, Ureas). Alkyleneamines react with acids, esters, acid anhydrides or acyl hahdes to form amidoamines and polyamides. Various diamides of EDA are prepared from the appropriate methyl ester or acid at moderate temperatures (25,26). 

Under more forcing conditions with acid anhydrides, EDA can form tetraacyl derivatives (29). However, much milder conditions or less active acylating agents are needed to obtain the monoamide essentially free of the diamide (30—32). 

The anticonvulsant primidone (1035) resembles phenobarbital but lacks the 2-oxo substituent. It was introduced in 1952 and has remained a valuable drug for controlling grand mal and psychomotor epilepsy. As might be expected, primidone is metabolized to yield phenobarbital (1034 X = 0) and C-ethyl-C-phenylmalondiamide (1036), both of which have marked anticonvulsant properties however, primidone does have intrinsic activity and an appropriate mixture of its metabolites has only a fraction of its activity (73MI21303). Primidone may be made in several ways, of which desulfurization by Raney nickel of the 2-thiobarbiturate (1034 X = S) or treatment of the diamide (1036) with formic acid (at 190 °C) seem to be the most satisfactory (54JCS3263). 

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