Isothiocyanates from primary amines

Amphetamine was extracted with ether from alkaline aqueous solutions (body fluids). If interfering compounds were present, the solution was first steam distilled, then the distillate was made alkaline and extracted. The ether extract was mixed with an equal volume of CS2, allowed to stand for 1 h and evaporated to a small volume. 

Mescaline (3,4,5-frimethoxyphenylethylamine) and STP or DOM (2,5-dimethoxy-4-methyl amphetamine) were extracted with ether from alkaline aqueous solution. The ether extracts were mixed with CSj and allowed to stand for several hours or heated at 50 C for 2 h, then evaporated to a small volume. 

The reactions with dopamine, norephedrine and noradrenaline were carried out in DMF. The solutions were mixed equal volumes of CS2 and TMSI, then warmed under erflux for 3h and evaporated to small volume. Pyridine, fotmamide and tetrahydrofuran were also satisfactory solvents for converting dopamine. 

The reaction mixtures were analyzed by GC with FID or ECD [48], by GC-MS and GC with mass-specific detection [49], by GC with combined positive- and negative-ion MS or mass specific detection [50] and by GC-FTIR spectrometry [60]. 

A solution containing Img of free base in 5 ml of EtOAc was shaken with 0.5 ml of CS2 for 30 min, the mixture was evaporated to dryness under reduced pressure and the residue was dissolved in EtOAc (1ml). Aliquots (1 pi) were used for GC on 1% SE-30 or 2.5% OV-225 on Gas-Chrom Q. 

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Indeed, this transformation has been developed into a procedure for the preparation of isothiocyanates from primary amines using hydrogen peroxide as the dehydrosulfurization reagent. It proceeds via the thiuram disulfide, although concentrations of the latter are always kept low (Fig. 8) (85). 

Figure 8. Proposed route for the preparation of isothiocyanates from primary amines.

N-Mono- and N,N-disubstituted UREAS AND THIOUREAS, 45, 69 N-Monosubstituted thioureas from primary amines and silicon tetra-isothiocyanate, 45, 69 N-Monosubstituted ureas from primary amines and silicon tetraisocyan-ate, 45, 69... 

Primary and secondary amines have been converted to dithiocarbamates, of which only those derived from primary amines undergo elimination of alkanethiol in the injection port to yield isothiocyanates [234] ... 

Isothiocyanates have been obtained directly from primary amines... 

Yavari, I., Souri, S., and Sirouspour, M. (2008). Efficient one-pot synthesis of unsymmetrical 2-thioparabanic acids from oxalyl chloride, benzoyl isothiocyanate, and primary amines. Synlett, 1633-1634. 

Dithiocarbamates generated from primary amines are generally less stable than their secondary amine counterparts, and can decompose to give the corresponding isothiocyanate (Eq. 6). 

Salts of dithiocarbamic acid can be prepared by the addition of primary or secondary amines to carbon disulfide. This reaction is similar to 16-9. Hydrogen sulfide can be eliminated from the product, directly or indirectly, to give isothiocyanates (RNCS). Isothiocyanates can be obtained directly by the reaction of primary amines and CS2 in pyridine in the presence of DCC. ° In the presence of diphenyl phosphite and pyridine, primary amines add to CO2 and to CS2 to give, respectively, symmetrically substituted ureas and thioureas ... 

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... 

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). 

PHA827). 3-Amino-6-phenylthieno[2,3-<7]pyrimidin-4-one-2(l H)-thione (17) was obtained similarly from isothiocyanate 15 (R1 = C02Et, R2 = H, R3 = Ph) via the thiosemicarbazide 16 (94PHA64). Isothiocyanate 15 [R1 = COPh, R2, R3 = (CH2)4] was reacted with hydrazine hydrate and various primary amines to give directly the 3-substituted 4-phenyl-2-thioxothieno[2,3-c/ pyrimidines 82b (90JHC269). 

Dielectrophilic species are 1,4-diketones, certain 1,3-dienes, a,B-unsaturated isocyanates, isothiocyanates, cyanates, and thiocyanates bearing electron-withdrawing (e.g., polyfluorinated and perfluorinated) substituents the most frequently used 1,1-dinucleophiles are water, potassium sulfide, primary amines, and ammonia. From this repertoire of building blocks many combinations are possible. Tetrakis(trifluoro-methyl)furans, thiophenes, and pyrroles have been synthesized from per-fluoro-3,4-dimethylhexa-2,4-diene on addition of water, potassium sulfide, or aniline (90CC1127) (Scheme 39). 

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