Carbon disulfide, dithiocarbamate synthesis

Considerably less is known about the chemistry of palladium and platinum 1,1-dithio complexes. Of late, there has been only one report that dealt with the synthesis of a large number of palladium dithiocar-bamates 392). Twenty-five yellow palladium dithiocarbamate complexes were obtained by reaction of PdCla with NaR2dtc in methanol solution. Several other reports have appeared in which a few dithiocarbamate complexes of palladium were synthesized. Thus, the novel [Pd (OH)2dtc 2], which is soluble in water, was isolated 393). The synthesis of optically active palladium(II) complexes of AT-alkyl-a-phen-ethyldithiocarbamates, similar to (XXIV), via the reaction between the optically active amine, CS2, and PdCl2, has been described. From ORD and CD spectra, it has been established that the vicinal contribution of a remote, asymmetric carbon center could give rise to optical activity of the d—d transitions of palladium 394). Carbon disulfide has been shown to insert into the Pt-F bond of [PtF(PPh3)3]HF2, and X-ray studies indicated the structure (XXIX). 

There is an enormous literature on thiocarbonyl compounds, due in part to the technical and industrial importance of many of them, including thioamides, thioureas, xanthates, dithiocarbamates and so forth. An excellent, and recent, general review is available.107 There are also specialized reviews germane to the present chapter Griffin, Woods, and Klayman2 discussed the use of thioureas in the synthesis of heterocycles the preparation of thiazoles from thioamides is included in a three-part volume on Thiazoles 108 the use of carbon disulfide in the synthesis of trithiones and related heterocycles has been reviewed by Mayer109 and Huisgen110 has reported numerous examples of 1,3-dipolar cycloadditions in which carbon disulfide was used. 

To increase the yields of the ring closure reactions, a new method was developed that was successfully applied for the synthesis of alicyclic fused systems of both the parent oxazolidine-2-thione and tetrahydro-1,3-oxazine-2-thione (85S1149). As an example, the synthesis of 2-thioxoperhydro-l,3-benzoxazine 103 is described. The dithiocarbamate 101, prepared from the amino alcohol 100, carbon disulfide and triethylamine, was treated with ethyl chloroformate in the presence of triethylamine, to give the thioxo derivative 103 via the transition state 102 (85S1149). In this way, the fused-skeleton thioxooxazines (91, X = S, 92) can be prepared with considerably higher yields (50-70%) than by the earlier methods (85S1149). 

Carbon disulfide is the starting point for dithiocarbamate synthesis via reaction with an amine... 

N-Bis(methylthio)methylene derivatives of amines (iminodithiocarbonates) were first introduced by Hoppe and Beckmann468 for the synthesis of a-amino acids from glycine. The A bis(methylthio)methyleneamines are prepared by reaction of a primary amine with carbon disulfide (HAZARD) in the presence of triethylamine and iodomethane to form a methyl dithiocarbamate derivative, which is then S-alkylated with a second equivalent of iodomethane in the presence of potassium carbonate as the base. Scheme 8,233 illustrates an alternative one pot procedure applied to the synthesis of /erf-butyl N-[bis(methylthio)-methylene]glycinate and its use in diastereoselective conjugate addition under... 

The formation of desaurins from ketones, carbon disulfide, and base 1275,1281,1282,1285-1290 believed to involve nucleophilic attack on a thioketene by the dianion of a 1,1-dimercaptoalkene, as shown for the synthesis of 572. Related syntheses involve the use of thiophosgene instead of carbon disulfide and the use of diazoalkanes or phosphonium and sulfonium ylides instead of a ketone and base. Treatment of perfluoroiso-butylene with fluoride ion and elemental sulfur in a dipolar, aprotic solvent ° °° or with sources of anionic sulfur (potassium sulfide, sodium hydrosulfide,potassium thiocyanate,sodium thiosulfate, dithiocarbamate salts, dithiophosphate salts ) give the dimer (573) of bis(trifIuoromethyl)-thioketene. Similarly, other 2,4-bis(methylene)-l,4-dithietanes are obtained by treating 2,2-dichlorovinyl ketones with anionic sulfur re-... 

Use of carbon disulfide has particular significance for the synthesis of dithiocarbamates and thioureas in thioacylation reactions. ... 

These are easily prepared by the reaction of amines with carbon disulfide (1) in the presence of alkali (Scheme 17).2 The synthesis of dithiocarba mates (4) was first reported by Debus in 1850. Dithiocarba mates (4) form metal chelates, and sodium dimethyl dithiocarbamate is used in quantitative inorganic analysis for the estimation of metals, e.g. copper and zinc. Dithiocarba mates are also employed as vulcanisation accelerators and antioxidants in the rubber industry, and as agricultural fungicides.3 The parent dithiocarbamic acids are unstable, decomposing to thiocyanic acid and hydrogen sulfide however, the salts and esters are stable compounds. Dithiocarba mates (4) are oxidised by mild oxidants to the thiuram disulfides (38) (Scheme 17). 

Cadmium decreases testosterone production by preventing the synthesis of cholesterol, a precursor of all steroid hormones. Other chemicals that interfere with steroid hormone synthesis include aminoglute-thimide, cyanoketone, and ketoconazole. Copper chelating compounds, such as dithiocarbamates, metam sodium, and carbon disulfide, suppress the conversion of dopamine to norepinephrine and subsequently to epinephrine. 

Thiram and other dithiocarbamates are metabolic poisons. The acute effects of thiram are very similar to that of carbon disulfide, supporting the notion that the common metabolite of this compound is responsible for its toxic effects. The exact mechanism of toxicity is still unclear, however it has been postulated that the intracellular action of thiram involves metabolites of carbon disulfide, causing microsome injury and cytochrome P450 disruption, leading to increased heme-oxygenase activity. The intracellular mechanism of toxicity of thiram may include inhibition of monoamine oxidase, altered vitamin Bg and tryptophan metabolism, and cellular deprivation of zinc and copper. It induces accumulation of acetaldehyde in the bloodstream following ethanol or paraldehyde treatment. Thiram inhibits the in vitro conversion of dopamine to noradrenalin in cardiac and adrenal medulla cell preparations. It depresses some hepatic microsomal demethylation reactions, microsomal cytochrome P450 content and the synthesis of phospholipids. Thiram has also been shown to have moderate inhibitory action on decarboxylases and, in fish, on muscle acetylcholinesterases. 

Dithiocarbamic acids, R2NC(S)SH, are rather unstable and seldom isolated or used as such. Usually their alkali metal or (substituted) ammonium salts are prepared for further use as starting materials in the synthesis of various metal complexes or organometallic derivatives. The most common is the reaction of primary or secondary amines with carbon disulfide in alkaline medium. 

The reaction of carbon disulfide with 1,2-alkylene diamines (I) yields N-(2-aminoethyl) dithiocarbamic acids (II) which split off hydrogen sulfide thermally to give imidazolidine-2-thiones (III) (Hofmann-process). The simplest example, the reaction of carbon disulfide with ethylenediamine, is described in Organic Synthesis (5). The reaction is general for N,N -dialkyl-, N,N -diaryI, as well as for N,N -bis-(arylakyl) ethylene diamines. The rate of reaction is determined by the basicity of the diamine. Electron-donor substituents in the para-position of N-aromatically substituted ethylene diamines accelerate dithiocarbamate formation electron-acceptor groups retard it. 

Both ( )- and (Z)-allyl dithiocarbamates have been stereoselectively prepared in high yields from acetates of MBH adduets in catalyst-free one-pot three-component coupling reactions of carbon disulfide and amine in water under a mild and green procedure (Scheme 3.152). The reaction pathway involves the nucleophilic displacement (-S n2 ) of MBH acetates by dithio-carbamate anions. The utility of these allyl dithiocarbamates has been demonstrated in the synthesis of 3,5-dibenzyl-l,3-thiazines derivatives 344 and 345 (Scheme 3.153). ... 

The aliphatic amines are valuable intermediates for chemical synthesis applications, Reaction of ethylamine with cyanuric chloride yields triazine-type herbicides, Diethylamine is used in the preparation of vulcanization accelerators where reaction with carbon disulfide yields a dithiocarbamate. Triethyl-amine is used as an acid acceptor in chemical syntheses and as a salt former in various purification processes. The amine is used as a corrosion inhibitor in aqueous systems, as a catalyst in polyurethane applications, in textile and photographic applications, and in anodic electrocoating. 

CS2 as a type of liquid sulfur source was applied in benzothiazole synthesis as well. In 2011, Ma and co-workers found that copper salt can catalyse the reaction between 2-haloanilines and dithiocarbamate, which was generated in situ from amines and carbon disulfide (Scheme 2.145a). ° 2-N-Substi-tuted benzothiazoles were produced in good yields. Later on, they found that thiols can be applied as well. Condensation of carbon disulfide with thiols in... 

Recently, Ma et al. developed a three-component reaction for the synthesis of 2-A -substituted benzothiazoles 107 via the copper-catalyzed coupling of 2-iodoanilines, carbon disulfide, and secondary amines (Scheme 3.56) [149]. In these reactions, the condensation of CS with an amine in the presence of a base generates dithiocarbamate salts XXXV, which undergo coupling with 2-iodoanilines to give XXXVI and subsequent intramolecular condensation and elimination to afford the substituted benzothiazoles 107. 

In the same manuscript, the authors described the synthesis of polyfunctionalized Z-dithiocarbamates 61, which are important building blocks due to their numerous biological activities [59]. This 6-MCR proceeded through a one-pot and six-component Ugi/nucleophilic addition sequence in high yields (Scheme 7.25). The main difference with the aforementioned 5-MCR was the use of carbon disulfide and an amine for the nucleophilic addition. 

It is not clear when dithiocarbamates were first prepared, but certainly they have been known for at least 150 years, since as early as 1850 Debus reported the synthesis of dithiocarbamic acids (1). The first synthesis of a transition metal dithiocarbamate complex is also unclear, however, in a seminal paper in 1907, Delepine (2) reported on the synthesis of a range of aliphatic dithiocarbamates and also the salts of di-iTo-butyldithiocarbamate with transition metals including chromium, molybdenum, iron, manganese, cobalt, nickel, copper, zinc, platinum, cadmium, mercury, silver, and gold. He also noted that while dithiocarbamate salts of the alkali and alkali earth elements were water soluble, those of the transition metals and also the p-block metals and lanthanides were precipitated from water, to give salts soluble in ether and chloroform, and even in some cases, in benzene and carbon disulfide. 

Bereman and Nalewajek (72) described the synthesis of dithiocarbamates derived from indole, indoline, carbazole, and imidazole (Fig. 7). Again, the amides are initially generated in dry THF upon addition of potassium metal, and later addition of excess carbon disulfide at —78°C leads to generation of the potassium salts of the dithiocarbamates (Eq. 4). While the indoline and imidazole derivatives are relatively air stable, the others are extremely air sensitive decomposing in a matter of minutes. The potassium salt of the dithiocarbamate derived from 2,2 -dipyridylamine (Fig. 7) has been prepared in a similar fashion, and while air stable, it is extremely hygroscopic (73). 

The bis(2,2,2-triiluoroethyl) dithiocarbamate salt, NaS2CN(CH2CF3)2, is a valuable precursor to a range of complexes that find widespread uses in analytical chemistry (74-82). It can be readily prepared from the amine using sodium amide as the base in the presence of carbon disulfide (Eq. 5) (76, 75), and a synthesis of the lithium salt has also been reported (83, 84). 

Ma et al. developed a copper-catalyzed cascade condensation/S-arylation/hetero-cyclization for the three-component synthesis of 2-iV-substituted benzothiazoles 113 from amines, carbon disulfide, and 2-haloanilines (Scheme 5.75) [78]. The first step in this process is the reaction between amine and carbon disulfide in the presence of bases to form dithiocarbamate salt A. Then, the in situ-generated A undergoes... 

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