Naoaki Fukada

Reactions of β-imino-nitriles and -esters with carbon disulphide. A new synthesis and some reactions of 2-cyano-3-imino-dithiocarboxylic acids

Treatment of a series of β-imino-nitriles with carbon disulphide and sodium t-pentyl oxide at room temperature gave the corresponding 2-cyano-3-imino-dithiocarboxylic acids, accompanied in some cases by pyrimidine-2,4-dithiones. β-lmino-β-arylpropiononitriles, when treated with carbon disulphide in dimethylformamide at low temperature, afforded 1,3-thiazine-2,6-dithiones. When an excess of sodium t-pentyl oxide was used in this reaction, β-iminobutyronitrile yielded pyrido[4,3-d][1,3]thiazine-2,4,5,7(1H,8H)-tetrathione. β-lmino-β-phenylpropiononitrile, under the same conditions, gave a 1,5-diazocine-2,6(1H,5H)-dithione. β-lmino-esters in this reaction, afforded 1,3-thiazine-2,6-dithiones. Reactions of 2-cyano-3-imino-dithiocarboxylic acids with methyl and phenyl isocyanates, ethyl and phenyl isothiocyanates, picryl chloride, and hydrazine have also been studied.

Oxidation and bimolecular condensation reactions of 2-alkyliminocyclopentanedithiocarboxylic acids, 2-oxocyclopentanedithiocarboxylic acids, and 3-methyl-5-oxo-1-phenyl-Δ2-pyrazoline-4-dithiocarboxylic acid

The 2-oxocyclopentanedithiocarboxylic acids (9) and (10) and 3-methyl-5-oxo-1-phenyl-Δ2-pyrazoline-4-dithiocarboxylic acid (13), on oxidation, gave the 3,5-bis-(2-oxocyclopentylidene)-1,2,4-trithioles (11) and (12) and 3,5-bis-(3-methyl-5-oxo-1-phenyl-Δ2-pyrazolin-4-ylidene)-1,2,4-trithiole (14), respectively. The 2-alkyliminocyclopentanedithiocarboxylic acids (1)–(4), under similar conditions, underwent normal oxidation to the bis-(2-alkyliminocyclopentylthiocarbonyl) disulphides (5)–(8). The acid (9) afforded 6,7-dihydro-2-(2-oxocyclopentylidene)cyclopenta[d][1,3]dithiin-4(5H)-thione (15) when treated with dimethylformamide alone, and 2,4-bis-(2-oxocyclopentylidene)-1,3-dithietan (16) when treated with dimethylformamide and an acyl chloride. 2,4-Bis-(3-methyl-5-oxo-1-phenyl-Δ2-pyrazolin-4-ylidene)-1,3-dithietan (17) was likewise obtained from the acid (13).

Some reactions of 2-oxocyclopentanedithiocarboxylic acid and 3-methyl-5-oxo-1-phenyl-Δ2-pyrazoline-4-dithiocarboxylic acid

The title dithiocarboxylic acids, (1) and (6) respectively, were obtained by substitution reactions of the corresponding cyclic ketones with carbon disulphide in the presence of aqueous alkali. The acid (1) reacted with hydrazine to give 1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3(2H)-thione (2); the acid (6) simply afforded the hydrazide (11). Treatment of the acid (6) with aldehydes yielded the 1,3-dithietan-2-ylidenepyrazolines, (7)–(10). The acids (1) and (6) both gave benzodithiol-2-ylidene derivatives [(3), (4), and (12)] when treated with 2,4-dinitrochlorobenzene or similar reagents.

Stabilities and transfer activity coefficients from water to polar nonaqueous solvents of 1,2-bis[2-(2-methoxyethoxy)ethoxy]benzene- and benzo-18-crown-6-cation complexes

Formation constants (K ML) for 1:1 complexes of 1,2-bis[2-(2-methoxyethoxy)ethoxy]benzene (AC·B18C6), a linear counterpart of benzo-18-crown-6 (B18C6), and B18C6 with various mono- and divalent cations were determined in water at 25°C by conductometry; the K ML value for the B18C6-Li+ complex was also determined in acetonitrile. By using the K ML and literature values, transfer activity coefficients of the AC·B18C6- and B18C6-alkali metal ion complexes from water to polar nonaqueous solvents were calculated. The selectivity order in water of AC·B18C6 for univalent cations is different from that of B18C6, but for bivalent cations they are almost the same. For the same cation, the aqueous log K ML value is lower for AC·B18C6 than for B18C6 except for size-misfitting smaller cations (H+, Li+, Cd2+). In general, cyclization of the two binding-arms of AC·B18C6 increases the selectivity and stability for the cations in water. Although AC·B18C6 is always less hydrophilic than B18C6, the AC·B18C6-alkali metal ion complex is more hydrophilic than the corresponding B18C6 complex. It follows that the alkali metal ion in the AC·B18C6 complex is less effectively shielded and dehydration of AC·B18C6 upon complexation in water is less efficient, compared with B18C6. Hydrogen bonding between AC·B18C6 or B18C6 and water causes the unexpectedly lowest aqueous stability of the AC·B18C6- or B18C6-alkali metal ion complex among all the solvents. The same holds for the stabilities of the other metal ion complexes with AC·B18C6 or B18C6.

Solvent extraction of univalent and bivalent metal picrates with 1,2-bis[2-(2-methoxyethoxy)ethoxy]benzene (noncyclic crown ether) into CHCl3

The overall extraction equilibrium constants, Kex, of 1:1:m complexes of 1,2-bis[2-(2-methoxyethoxy)ethoxyjbenzene (AC · B18C6) with uni- and bivalent metal picrates, MAm were determined at 25°C between CHCl3 and water, and thereby the ion-pair complex-formation constants,KMLA,o, of AC · B18C6 with the univalent metal picrates in CHCl3 were calculated. The AC · B18C6 is an open-chain analog of benzo-18-crown-6 (B18C6). The equilibrium constants of AC · B18C6 were compared with those of B18C6. Kex sequences of AC · B18C6 for uni- and bivalent metals are Tl+ > K+ > Rb+ > Cs+ > Na+ > Li+ and Pb2+ > Ba2+ > Sr2+, respectively. The same extraction-selectivity was observed for B18C6, but the extractability of AC · B18C6 for the same cation is much lower than that of B18C6; the extraction selectivity of AC · B18C6 for alkali metals is lower than that of B18C6. TheKMLA,o sequence of AC · B18C6 is K+ > Rb+ > Tl+ > Cs+ ≌ Na+, which is consistent with that of B18C6. ButKMLA,o of AC · B18C6 is much smaller than the correspondingKMLA,o of B18C6; the selectivity of AC · B18C6 among alkali metal picrates in CHCl3 is lower than that of BI8C6. This reflects the difference in the structures between AC · B18C6 (acyclic and flexible) and B18C6 (cyclic and rigid).

Formation of 3-substituted 2-iminocyclopentanedithiocarboxylic acids and N-[amino(dimercapto)methyl]-2-methylcyclopentanimine from 2-substituted cyclopentanones. Some reactions of the imino-dithiocarb-oxylic acids

2-Ethyl, 2-isopropyl. 2-cyclopentyl. and 2-cyclopentylidenecyclopentanones, when treated with carbon disulphide and ammonia, gave the corresponding 3-substituted 2-iminocyclopentanedithiocarboxylic acids (5)–(7) and (9). Under the same conditions, 2-methylcyclopentanone gave 2-imino-3-methylcyclopentanedithiocarboxylic acid (2), and N-[amino(dimercapto)methyl]-2-methylcyclopentanimine (3), and 2-isopropylidenecyclopentanone gave7a-amino-4,4-dimethylperhydrocyclopenta[e][1,3]thiazine-2-thione (8). Reactions of the 2-iminocyclopent-anedithiocarboxylic acids with hydrazine, thiosemicarbazide, picryl chloride, and phenyl isothiocyanate have also been investigated.

Stabilities in water and Gibbs free energies of transfer from water to nonaqueous solvents of alkali metal ion complexes with 1,2-bis[2-(2-methoxyethoxy)ethoxy]benzene (acyclic polyether)

Stability constants of 1:1 complexes, ML+ (M+ and L being a univalent metal ion and a ligand, respectively), of Na+ and K+ with 1,2-bis[2-(2-methoxyethoxy)ethoxy]benzene (AC · B18C6), a linear counterpart of benzo-18-crown-6 (B18C6), were determined in water at 25°C by conductometry. The stability of ML+ is lower for AC · B18C6 than for B18C6 because of the macrocyclic effect, and AC · B18C6 is selective for Na+ in contrast to B18C6. Also determined were Gibbs free energies of transfer (ΔGH2O→S°) from water to nonaqueous solvent S (S=acetonitrile, propylene carbonate and methanol) of AC · B18C6 and B18C6 at 25°C through measurements of the distribution constants between tetradecane and the polar solvent. From these data as well as the literature values of KML in the nonaqueous solvents and of ΔGH2O→S° of M+, the ΔGH2O→S° values of ML+ complexes of the alkali-metal ions with AC · B18C6 and B18C6 were calculated. The ΔGH2O→S° values of M+ are positive but those of ML+ and L are negative in all the systems. This indicates that, although the M+ ions are more soluble in water than in the nonaqueous solvents, when the M+ forms a complex with the lipophilic L, the complex becomes more soluble in the nonaqueous solvent than in water. The lipophilicity of AC · B18C6 is higher than that of B18C6, but the reverse holds for the ML+ complexes. It was concluded that AC · B18C6 shields the M+ ions less effectively in the complexes from the surrounding solvents than B18C6.

Reaction of carbon disulphide with cyclic amides and related compounds. Free N-acyl- and N-carbamoyl-dithiocarbamic acids

2-Pyrrolidone, 2-piperidone, Iµ-caprolactam, imidazolidin-2-one, imidazolidine-2,4-dione, and 2,5-dioxopiperazine, after treatment with sodium hydride or in the presence of alkali, reacted with carbon disulphide to give the respective 1-dithiocarboxylic acid and/or 1,3-bisdithiocarboxylic acid which were readily esterified. The stable crystalline free acids could be easily isolated in the case of the five-membered ring compounds.

Preparation of β-alkylimino-dithiocarboxylic acids

The title compounds were prepared by the reaction of carbon disulphide with the product obtained by refluxing a mixture of a ketone and a primary amine with potassium fluoride. Ketones in which α-position is sterically hindered were reluctant to undergo this reaction.

Addition reaction of 2-iminocyclopentanedithiocarboxylic acid with Schiff's bases: a novel route to the synthesis of 1,3-thiazine derivatives

2-Iminocyclopentanedithiocarboxylic acid (1) reacted with Schiffs bases to give the adduct esters (2). The esters were easily converted into the corresponding thiazines (3a), (3e), and (3f) with accompanying elimination of anilines. In the case of cyclopentylideneanilines, the esters could not be isolated, instead the thiazine (4) was directly obtained.