Amides ammonia equivalent reactions

A facile one-pot, Cul-catalyzed amidation/hydrolysis leads to net Ar-NH2 bond formation using the ammonia equivalent in crystalline 2,2,2-trifluoroacetamide. Aryl iodides react in DMF at 45 °C, while bromides require dioxane at 75 °C. DMEDA (iV,iV-dimethylethylenediamine) is the ligand of choice. Yields are consistently good, although or/Ao-substitution is not tolerated. Both eleetron-rich and -poor substrates can be used with iodides imder the milder conditions. Simple addition of methanol and water to the reaction mixture with continued stirring leads to the desired corresponding anilines. 

The first Mo(CO)6-promoted, microwave-assisted protocols for aminocarbonylation of aryl bromides and iodides to primary benzamides were presented in 2006 [34]. Hydroxylamine hydrochloride was used as a solid ammonia equivalent as it was found that hydroxylamine was smoothly reduced in situ by Mo(CO)6, generating free ammonia that could undergo the carbonylation. The conditions found suitable for this reaction included an aryl halide, Mo(CO)6, NH2OH HCI, 1,2, DBU, and DIEA in dioxane followed by 20 min of microwave heating at 110 °C for Ar-I and 150 °C for Ar-Br. Eight primary benzamides were synthesized from aryl bromides in 70-81% yield and the same amides from aryl iodides in 76-84% yield (Scheme 4.20). The method was also used in the synthesis of weak HIV-1 protease inhibitors (Scheme 4.21) [34]. 

Note that the synthesis of this terminal alkyne requires a total of rAree equivalents of base. The double dehydrohalogenation itself requires two equivalents. However, a third equivalent is required because, as the alkyne forms, its acidic hydrogen atom reacts with the amide ion to convert the alkyne to its conjugate base. Without the extra equivalent of amide ion, the reaction would not go to completion. The water in the workup step acts as an acid to protonate the alkynide and to convert any excess amide ion to ammonia. 

Reaction with ammonia and amines (Section 20 14) Acid an hydrides react with ammonia and amines to form amides Two molar equivalents of amine are required In the example shown only one acyl group of acetic anhydride becomes incor porated into the amide the other becomes the acyl group of the amine salt of acetic acid... 

Triazole has been prepared by the oxidation of substituted 1,2,4-triazoles, by the treatment of urazole with phosphorus pentasulfide, by heating equimolar quantities of formyl-hydrazine and formamide, by removal of the amino function of 4-amino-l,2,4-triazole, by oxidation of l,2,4-triazole-3(5)-thiol with hydrogen peroxide, by decarboxylation of 1,2,4-triazole-3(5)-carboxylic acid, by heating hydrazine salts with form-amide,by rapidly distilling hydrazine hydrate mixed with two molar equivalents of formamide, i by heating N,N -diformyl-hydrazine with excess ammonia in an autoclave at 200° for 24 hours, and by the reaction of 1,3,5-triazine and hydrazine monohydrochloride. ... 

This procedure, which is based on the work of Ishii and co-workers, affords a mild and general method for converting a wide variety of esters to primary, secondary, and tertiary amides (Table 1). While the preparation of the tertiary amide, N,N-dimethylcyclohexanecarboxamide, described here is carried out in benzene, aluminum amides derived from ammonia and a variety of primary amines have been prepared by reaction with trimethylaluminum in dichloromethane and utilized for aminolysis in this solvent. Although 1 equivalent of the dimethylaluminum amides from amines was generally sufficient for high conversion within 5-48 hours, best results were obtained when 2 equivalents of the aluminum reagent from ammonia was used. Diethyl-aluminum amides can also effect aminolysis, but with considerably slower rates. 

Homologues of ethoxyacetylene can be obtained by reaction of the metallated ethynyl ether in liquid ammonia with primary alkyl bromides and iodides 167]. Because of their better solubiliiy, the lithium compounds are preferred over their sodium and potassium analogues, lithium ethoxyacetylide is generated from the readily accessible 2-bromovinyl ethyl ether and two equivalents of lithium amide. This starting compound is obtained as a mixture of the E-and Z-isomer. When this mixture is heated with powdered KOH, only the Z-isomer is converted into ethoxyethyne. Alkali amides are able to conven both isomers into ethoxyethyne and its alkali compounds. A possible explanation for this violation of the "rule of... 

Ethyl 1-hydroxycyclohexylacetate has been prepared by the Reformatsky reaction of cyclohexanone with zinc and ethyl bromoacetate (56-71 %)3 and by the condensation of ethyl acetate with cyclohexanone in liquid ammonia using two equivalents of lithium amide (69%).4... 

Wilmarth et al. (1953) compared the rates of isotope exchange reactions between molecular hydrogen and equivalent solutions of KOD in D20 and KND2 in ND3 and concluded that the second reaction is faster than the first by a factor of 1014. This shows the exceedingly high catalytic activity of the potassium amide solution in liquid ammonia. 

Cyclopropen-1-yl sodium derivatives are also readily prepared. Thus reaction of cyclopropene with one equivalent of sodium amide in liquid ammonia leads to 1-sodiocyclopropene which is alkylated by haloalkanes 77,78 reacts with ketones to produce tertiary alcohols and opens epoxides to produce 2-cyclopropenyl-ethanols in moderate to good yields79). Moreover, on reaction with two equivalents of base followed by haloalkane, 1,2-dialkylated species are obtained sequential reactions can also be used to produce unsymmetrically substituted cyclopropenes78). Reaction with a deficiency of sodium amide can also cause addition of the cyclopro-penyl anion to unreacted cyclopropene, leading to products derived from the 2-cyclo-propylcydopropen-l-yl anion and to 1,2-dicyclopropylcyclopropene 77). 

Isatin reacts with ammonium hydroxide or ammonium acetate to furnish a mixture of compounds. Amongst them are isamic acid and its corresponding amide, isamide. Since 1877 there had been a discussion as to their structure, which in 1976 was finally elucidated, by Sir John Comforth on the basis of chemical and spectroscopic data228. Isamic acid can be regarded as a dimer formed by the addition/condensation of one equivalent of ammonia with two equivalents of isatin. This intermediate suffers lactonization and subsequent conversion to isamic acid by an internal nucleophilic attack, where upon the acid is converted to isamide by reaction with a second equivalent of ammonia. 1-Methylisatin reacts similarly, furnishing N-methylisamic acid (Scheme 51). 

Other bases have been employed to deprotonate these complexes 63). The singly deprotonated complex [Os(en-H)(en)2]l2 can be obtained by reaction of [Os(en)3]l3 with one molar equivalent of potassium or potassium amide in liquid ammonia, with a six-fold molar excess of KOC2H5 in ethanol, or with a four-fold molar excess of KOH in ethanol. However,... 

Triglycerides can be converted to the corresponding amides using C. antarctica, with ammonia in fe/t-butyl alcohol.228 Olive oil gave a 90% yield of oleamide in 72 h at 60°C. Industrial reactions of this type are run at 200°C. The enzyme can also be used to convert oleic acid to oleamide in 90% yield in tert-amyl alcohol containing two equivalents of mbutyl alcohol. The intermediate butyl ester is formed in situ. Candida antarctica lipase can also be used to prepare monoesteramides from dimethyl succinate... 

A similar phenomenon has been reported by Sugiyama and coworkers, who found that the vinylogous amide (23) reacts with benzaldehyde to give (24) as the sole product (equation 90). When (23) is treated with two equivalents of sodium amide in ammonia, followed by treatment with benzaldehyde, aldol (25) is formed in 25% yield. Although the authors invoke a dianion in the latter reaction, it is unlikely that one could be formed under the reaction conditions used. Instead, it is likely that deprotonation at the endocyclic a-position is preferred kinetically, and that this leads to the product observed with NaNH2/NH3 (irreversible enolate formation). Reaction of this enolate must be slow, for steric reasons, as witnessed by the low yield in the aldol reaction. Under conditions of enolate equilibration, the more stable extended dienolate is produced. 

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