Amines, preparation from isothiocyanates

Amines, preparation from isothiocyanates, 18, 5 from ketones, 17, 76 m-Aminobenzaldehyde, 13, 28... 

A similar reaction has been more recently described by other authors. Thioureas 89—the intermediates in the preceding reaction—were prepared from isothiocyanate 88 and amines. Benzo-TAs 90, which contain substituents on the exocyclic nitrogen atom, were obtained (92MI1) (Scheme 28). 

Thioureas are most commonly prepared from reaction of isothiocyanates with amines. Also there are some reports on reactions of anime or carbodiimides with several thionating reagents. AA -Disubstituted thioureas bearing double NH groups have been developed as sensors, and as catalysts because of their hydrogen bonding ability. A,A -Disubstituted thiourea-linked sugar chains have been prepared by the reaction of isothiocyanate with amine. 

Other approaches to tetrazoles were also recently published. Primary and secondary amines 195 were reacted with isothiocyanates to afford thioureas 196, which underwent mercury(II)-promoted attack of azide anion, to provide 5-aminotetrazoles 197 . A modified Ugi reaction of substituted methylisocyanoacetates 198, ketones, primary amines, and trimethylsilyldiazomethane afforded the one-pot solution phase preparation of fused tetrazole-ketopiperazines 200 via intermediate 199 <00TL8729>. Microwave-assisted preparation of aryl cyanides, prepared from aryl bromides 201, with sodium azide afforded aryl tetrazoles 202 . 

Dipolar cycloaddition reactions, of nitrones to olefins, 46, 97 of 3-phenylsydnone, 46, 98 Dispiro[5.1.5.1]tetradecane-7,14-dione, photolysis to cyclohexylidene-cyclohexane, 47, 34 preparation from cyclohexanecarbonyl chloride and triethylamine, 47, 34 Displacement of bromine from 1-bromo-2-fluoroheptane to give 2-fluoro-heptyl acetate, 46, 37 N,N -Disubstituted formamidines from triethyl orthoformate and primary amines, 46, 41 N,N-Disubstituted thioureas from secondary amines and silicon tetra-isothiocyanate, 45, 69 N,N-Disubstituted ureas from secondary amines and silicon tetraiso-cyanate, 45, 69... 

The synthesis of 6-substituted derivatives 626 was achieved via reaction of 2-substituted-5-aminopyridine-4-car-boxylic acids and formamidine acetate in boiling 2-methoxyethanol <1996J(P1)2221>. The pyrido[3,4- lpyrimidinone 628 was prepared by amination of the thioureido derivative 627 with diisopropylamine followed by cyclization in boiling DMF <2004FRP2846657>. Pyridine 627 was prepared from the corresponding 3-amino derivative with ethoxycarbonyl isothiocyanate in DMF. 

This is a general method for the preparation of alkyl thioureas. Ethylthiourea, m.p. 103-106°, has been prepared from ethyl isothiocyanate in the same manner. Di- and tri-alkyl thioureas may be prepared from alkyl isothiocyanates in a similar manner by substituting an equivalent amount of an amine solution in place of the ammonium hydroxide. Thus, sym -dimethylthiourea is prepared from methyl isothiocyanate and methylamine solution. A solution of dimethylamine and methyl isothiocyanate gives trimethylthiourea. 

Isothiocyanates can be prepared from support-bound primary amines by treatment with thiophosgene [14] or synthetic analogs thereof (Entry 5, Table 14.2). In an alternative two-step procedure, the amine is first treated with CS2 and a tertiary amine to yield an ammonium dithiocarbamate, which is subsequently desulfurized with TsCl or a chloroformate (Entry 6, Table 14.2 Experimental Procedure 14.1). Highly reactive acyl isothiocyanates have been prepared from support-bound acyl chlorides and tetra-butylammonium thiocyanate (Entry 7, Table 14.2). These acyl isothiocyanates react with amines to give the corresponding 7V-acylthiourcas, which can be used to prepare guanidines on insoluble supports (Entry 6, Table 14.3). 

To a stirred solution of 74.6 g (0.5 mol) of benzylisothiocyanate in 500 mL toluene was added dropwise 46.6 g (0.5 mol) of aniline. The solution was refluxed 18 hours. After cooling, the reaction mixture was concentrated under reduced pressure. The residue was recrystallized from an appropriate solvent to yield N-phenyl-N -benzylthiourea. Isothiocyanates which are not commercially available may be prepared from aliphatic or aryl primary amines by the following methods Kurita and Iwakura, Org. Synth. 59, 195 Jochims, Chem. Ber. 101, 1746 (1968) or Castro, Pena, Santos, and Vega, J. Org. Chem. 49, 863 (1984). 

The same approach is taken to prepare 4-amino-7-((5)-2,3-dihydroxypropyl)pyrrolo[3,2-aT py-rimidine <91JCS(P1)195>. A variation of this approach used to prepare nonnucleoside derivatives proceeds via the activated amines (159), derived from the corresponding amine and benzyl isothiocyanate, which is cyclized with methanolic ammonia to yield the derivatives (160) (Equation... 

Condensation reaction between active methyl and methylene compounds and S-alkylated thioureas provides another useful synthetic pathway to the 1,1-enediamines. Rajappa and coworkers20 reported that nitromethane condensed with S-methylated thioureas 72, prepared from the reaction of amines and methyl isothiocyanate followed by S-methylation, to form asymmetric nitro 1,1-enediamines 73 (Scheme 5). 

It appears, then, that isocyanate and isothiocyanate CDAs are useful in LC resolutions of amines. Several of these agents are commercially available, and many others can be readOy prepared from a variety of commercially available optically active primary amines. The stereochemical stability of these CDAs is excellent, their reaction with amines is rapid and convenient, and the derivatives are readily and sensitively detected. These reagents are likely, therefore, to enjoy continued popularity. 

Tetramethylfluoroformamidinium hexafluorophosphate. The reagent is prepared from tetramethylurea by consecutive reactions with POCI3, HPFjj, and KF, and finds use in mediating the condensation of acids and hydrazine (to form hydrazides) and of amines and CSj in the presence of EtjN (to form isothiocyanates). 

In primary synthesis 2-perimidinamines (660) can be prepared from the naphthalene diamine with bromocyanogen or cyanamide (Scheme 106). 2-Anilino derivatives have been obtained in reactions with aryl isothiocyanates. 2-iV,7V-Dimethylamino derivatives (662) have been obtained via the alkylated amine (661) using dimethylamino(trichloro)methane. Nucleophilic substitution by amine readily occurs in the 2-position when carrying a halo, sulfenyl, or sulfonyl substituent <81RCR816>. 

Synthesis of 2-thioxotetrahydropyrimidin-4-(lH)-ones Libraries of 2-thioxotetrahy-dropyrimidin-4-(lH)-ones can be prepared by multicomponent reaction of amine, isothiocyanate, and yS-dielectrophile components (Scheme 7.23). [PEG -RMIM]X ionic liquids have been used in this reaction with microwave irradiation (Scheme 7.24) [75]. In a step-by-step approach, treatment of [PEG -RMIM]X with acryloyl chloride provided a supported acryloyl ionic liquid phase which was reacted with an amine and then isothiocyanate to give a thiourea. Cyclization-cleavage from the ionic liquid support to give the desired 2-thioxotetrahydropyrimidin-4-(lH)-one was achieved by using low-power microwaves at 120 °C for 15-45 min in the presence of diethylamine. 

A series of atropisomeric thioureas was prepared from optically pure isothiocyanates 397f and 398d with primary amines. Atropisomeric ureas were prepared by reacting 397e or 398c with various isocyanates. Tlie resulting ureas and thioureas were used as neutral enantioselective anion receptors for N-protected amino acid tetrabutylammonium salts (06CHI762). 

A) Bis-thioureas prepared by mechanochemicai ciick-type reaction between amines and aromatic isothiocyanates. (B) Stoichiometric controi in LAG mechanosynthesis of stericaiiy congested mono- and bis-thioureas from o-phenyienediamine. 

Active hydrogen compounds such as alcohols, thiols, amides, urethans, and sulfonamides can be alkylated by N-vinyl-amides, -urethans, or -sulfonamides in high yields. A one-step conversion of ar. nitro compounds to isocyanates has been reported Aliphatic isothiocyanates can be prepared from amines and carbon disulfide with dicyclohexylcarbodiimide under remarkably mild conditions... 

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