Efficient synthesis of tertiary amines from secondary amines

Reliable N-alkylations of secondary amines have been developed. By using DIAD and TPP (or PS-TPP) a variety of secondary amines can be converted to the corresponding tertiary amines in good to excellent yields with diverse alkylhalides; no formation of quaternary amine salts are observed. These protocols are amenable to combinatorial chemistry libraries, and are also useful for the syntheses of secondary amines by an acid lysis of the cleavable tertiary amino resins.     

Prodrugs for amines

The purpose of this work is to review the published strategies for the production of prodrugs of amines. The review is divided in two main groups of approaches: those that rely on enzymatic activation and those that take advantage of physiological chemical conditions for release of the drugs. A compilation of the most important approaches is presented in the form of a table, where the main advantages and disadvantages of each strategy are also referred.     

Chloroaromatic ether amines

A new and useful class of aromatic amines, based on multichlorinated benzenes and polyphenyls, has been developed. The amines are prepared by reacting the alkali metal salt of p-aminophenol with the chloroaromatics under nucleophilic substitution reaction conditions. Oligomeric amines can be obtained by condensing, e.g., the dialkali salt of bisphenol A and the alkali metal salt of p-aminophenol with the chloroaromatics. The products are mixtures of mono-, di-, and triamines, as a result of the complex functionalities of the chloroaromatics employed. Unique features of the amines include: (1) flame-retarding characteristics; (2) markedly reduced amine reactivity (compared with aniline); (3) thermal stability; (4) good solubility in the usual organic solvents.     

N-Dealkylation of aliphatic amines and selective synthesis of monoalkylated aryl amines

Highly selective alkyl transfer processes of mono-, di- and trialkyl amines in the presence of the Shvo catalyst have been realized; in addition, a general method for N-alkylation of aniline with di- and trialkyl amines is presented.     

New synthesis of trifluorinated amines from 1-bromopropargylic amines in superacid

Treatment of 1-bromopropargylic amines affords the corresponding 1,1,1-trifluoro in one step in HF-SbF₅ medium. 1-Bromo-1,1-difluoro or 2-bromo-1,1,1-trifluoro derivatives could also be prepared, depending on the reaction conditions.     

N-Anions of heteroaromatic amines

The alkylation of the N-anions of 2- and 4-aminopyridines, 1-aminoisoquinoline, and 2-amino-1-ethylbenzimidazole with C₂-C₄ alkyl halides in liquid ammonia leads to the formation of a mixture of the products of mono- and dialkylation at the NH₂ group (usually with a predominance of the latter). The role of stepwise processes and the yield of the dialkyl derivative increase on passing from alkyl bromides to iodides and from the heavier and branched radicals (C₄H₉, i-C₃H₇) to lighter radicals (C₂H₅).For communication V, see [1].Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 967–971, July, 1973.     

N-anions of heteroaromatic amines

The corresponding 2,2-azobenzimidazoles are formed by the oxidation of N-anions of 2-aminobenzimidazoLe and 1-methyl-2-aminobenzimidazole in liquid ammonia by means of potassium permanganate and potassium persulfate, as well as by oxidation with iodine in ether and autooxidation. In the case of the dianion of 1-methyl-2-aminobenzimidazole, it was demonstrated that the reaction proceeds through a step involving the formation of a hydrazo derivative. Quantitative yields of the previously unknown 2,2-hydrazobenzimidazoles were obtained by reduction of 1,1-dimethyl- and 1,1-diphenyl-2,2-azobenzimidazoles with phenylhydrazine.See [1] for communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 238–241, February, 1972.     

N-nitrosation of secondary amines

Conclusions A method was proposed for the N-nitrosation of secondary amines using N₂O₄ complexes in combination with tertiary amines or pyridine.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 226–227, January, 1978.     

Nitroethylene nitroethylation of amines

The nitroethylation of amiens is demonstrated to be a general reaction for bases in the pK_a range of 2 – 8 and that it proceeds through a key intra-molecular quenching step. The reaction, illustrated with aromatic amines, aliphatic amines and heterocyclic bases, offers $\text{inter}$$\text{alia}$ attractive routes to diverse heterocyclic systems.     

N-anions of heteroaromatic amines

The N-anions of 3-aminoindazole and its 1-substituted derivatives are oxidized by air oxygen to give 3,3-azo- and in some cases 3,3-azoxyindazoles.See [1] for communication VI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 952–955, July, 1977.     

NIS-promoted guanylation of amines

An efficient NIS-promoted guanylation reaction is described. This procedure allows the guanylation of primary and secondary amines through the reaction with di-Boc-thiourea and di-Boc-S-methylisothiourea, respectively. We demonstrated that the use of NIS compares favorably with existing methods and is an attractive alternative to heavy metal or Mukayama’s reagent activation.     

Ruthenium catalyzed synthesis of secondary or tertiary amines from amines and alcohols

Unsymmetrical secondary and tertiary amines are prepared by the ruthenium catalyzed reaction of alcohols with amines, which provides highly efficient method for synthesis of cyclic amines.     

N-anions of heteroaromatic amines

The methylation of N-anions of heteroaromatic amines with methyl iodide in liquid ammonia in most cases gives good yields of the corresponding dimethylamino derivatives. The reaction is of preparative value.See [1,2] for communications I and II.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1230–1237, September, 1971.     

Polymers of tertiary amines

Polymers of tertiary amines and their hydrochlorides of molecular weights in the range 300–2000 have been prepared, starting from trans-1,4-dichlorobutene-2, and primary amines. The polymers present interesting solubility properties. Variation of the reaction conditions leads to crosslinked insoluble polymers. Reaction of the soluble tertiary amine polymers with organic acid dichlorides leads to polymers of tertiary amine–amides, a new type of polymer.     

Electrochemical chlorination of amines

We have studied the laws governing the electrochemical chlorination of primary and secondary amines in aqueous solution on a ruthenium-titanium anode under conditions of diaphragm electrolysis. It was found that in order to ensure the most complete conversion of the amines into the corresponding chloramines it is necessary to add NaHCO₃ to the electrolyte [amine:NaHCO₃=1(1.5–3)]. Under the conditions of electrolysis primary amines are converted almost quantitatively into dichloramines. High yields of the N-chloro-derivatives of secondary amines can be obtained with high current densities and concentrations of NaCl.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 620–625, March, 1990.