Substituted thiocarbamates

The Bristol-Myers Squibb group has reported on the synthesis and bioactivity of various 3 -A-thiourea and 3 -A-thiocarbamate-substituted taxol analogs (308). The thiocarbamate analogs of general type 8.2.2 and 8.2.3 proved to be the most active, with greater activities in tubulin-assembly and cytotoxicity assays than taxol. The corresponding thiourea analogs were all less active than taxol. 

DiaminO 4,4-dimethyl-l,3,5-thiadiazine hydrobromide was isolated as by-product (418). Benzene sulfonates of cyanohydrin prepared from sodium cyanide and an halobenzoaldehyde, when treated with thiourea or its derivatives, afford 2,4-diamino-5-(p-halogenophenyl)-thiazole benzene sulfonates (447). Similarly, cyanoamido thiocarbamates obtained from cyanamide and isothiocyanates yield substituted 2,4-diaminothiazoles (598). 

Tandem radical cyclizations of suitably substituted /V-aryl thiocarbamates, thioamides and thioureas have been induced by exposure to 4 equiv. of tnj(trimethylsilyl)silane (TTMSH (TMS)3SiH), 1 equiv. of 2,2 -azo-/h.v-isobu-tyronitrile (AIBN as a radical initiator) and UV light to provide furoquinolines, isofuroquinolines, cyclopentaquinolines, indoloquinolines and related ring systems (Scheme 31).58... 

Formation of enantio- and diastereoenriched l-aza-4-oxa-7-thiabicyclo[3.3.0]octan-8-ones 453a and 453b was accomplished by ring closure of acyl-substituted. Y-bcnzyl thiocarbamates 452 in presence of Amberlyst 15 and 1,3-propanedithiol via a rearrangement of the oxazolidine ring (Equation 213) <2000JPR828>. 

As in the case of propachlor mercapturic acid sulfoxide, the biological significance of xenobiotic mercapturic acids that contain oxidized sulfur is not known. Casida et al. (39) have reported that sulfoxidation of some thiocarbamate herbicides is a beneficial step in the detoxication process. However, cysteine conjugates can exhibit adverse biological activities. Smith (40) has reviewed work on the metabolism of the toxic principle in kale and has shown that C-S lyase action on S-methylcysteine sulfoxide produces the toxic principle. Virtanen ( ) has reviewed the processes in other plants that lead to the production of compounds with biological activity from -substituted cysteine sulfoxides. 

This work has been extended from aryl and alkyl substituted systems (42) (R = aryl, alkyl) to analogues where R is an amino group, so giving access to synthetic equivalents of the nonstabilized amino nitrile ylides (45). Adducts were obtained in good-to-moderate yield with A-methyhnaleimide (NMMA), DMAD, electron-deficient alkenes and aromatic aldehydes (27,28), and with sulfonylimines and diethyl azodicarboxylate (29). Similarly the A-[(trimethylsilyl)methyl]-thiocarbamates (46) undergo selective S-methylation with methyl triflate and subsequent fluorodesilylation in a one-pot process at room temperature to generate the azomethine ylides 47. 

The sense and degree of asymmetric induction of the Pd(0)-catalyzed rearrangement of the cyclic and acyclic O-allylic thiocarbamates in the presence of BPA are the same as, or similar to, those in the Pd-catalyzed substitutions of the corresponding cyclic and acyclic racemic allylic carbonates and acetates with sulfinates and thiols. It is therefore proposed that Pd(0)/BPA reacts with the racemic O-allylic thiocarbamate with formation of a jt-allyl-Pd(II) complex, which contains as counter ion the corresponding thiocarbamate ion (Scheme 2.1.4.19) [23, 24]. Substitution of the jt-allyl-Pd(II) complex by the thiocarbamate ion gives the S-allylic thiocarbamate and the Pd catalyst. 

Research Focus Preparation of IV-substituted imide dialkyl-thiocarbamic acid esters as high-activity polymerization initiators. 

Freund,168-160 formulating the oxides as substituted 1,2,4-thia-diazolidines (152) and the sulphides as 1,2,4-dithiazolidines (155), justified the assignment of unlike hetero-nuclei on the grounds that sulfides were also obtainable by the action of bromine on alkyl dithiocarbamates (see below), while oxides were unobtainable by the corresponding reaction of alkyl thiocarbamates. Hantzsch and... 

A low-temperature study in superacid media of mono-, di-, and tri-protonated thiourea has been earned out.302 The experimental results were confirmed by theoretical calculations. Monoprotonation occurs at sulfur and, whereas the mono- and di-protonated forms are thermodynamically stable, the triprotonated ion is only kinetically stable. The pyrolysis of A-acctylthiourea and A.A -diacetyIthiourea (335) are ultimolecular first-order eliminations.83 Acid-catalysed ethanolysis of N,N -di- and tri-substituted aryl- and alkylaryl-thioureas gives 0-ethyl AAaryl thiocarbamates and amines.303 The acid-catalysed hydrolysis of thiourea was first order in thiourea and acid.304... 

Substitution of one or both of the oxygen atoms with sulfur in the above structure gives thiocarbamate. 

Substituted thiazolidin-4-ones (449) are easily prepared by the reaction between chloracetic acid, or its derivatives (447), and a thiourea, a thiosemicarbazide, or a mono-or di-thiocarbamate (448 Scheme 255). The same a-chloro acid derivatives react with metallic thiocyanates yielding an intermediate (450), the cyclization of which gives a 2-iminothiazolidin-4-one (451). In these reactions a -chloracetic acid may be replaced by... 

Cellulose reacts with isocyanates in anhydrous pyridine or with urea and substituted ureas at relatively high temperature to yield carbamates. The optimum carbamation reaction of microcrystalline cellulose with urea in a dry solid mixture has been studied [51]. In addition, a preferentially C6-modified cellulose carbamate derivative has been obtained [52]. Heating of cellulose with thiourea at 180°C yielded cellulose thiocarbamate [53]. Heat treatment of cellulose isocyanate products has been utilized for the production of urethanes [54]. When ceUuIose was treated with phenylisocyanate at 100 C in DMF in the presence of dibutyltin dilaurate and triethylenediamine, celiuiose bisphenylcarbamate was formed [55]. Treatment of cellulose with urea at temperatures at or above the latter s melting point (where urea decomposes into isocyanic acid and ammonia) has been employed for the production of cellulose carbamates fibers [56]. The advantages and disadvantages of using urea as an intermediate for production of fiber have been discussed [57]. 

Combination of a Diels-Alder reaction and a [3,3] sigmatropic rearrangement provides access to 1,4-substituted 2-cyclohexenyl derivatives75- 76,11 . Thus, Diels-Alder reaction of ( )-l,3-bu-tadienyl thiocyanate with methyl acrylate is followed by a [3,3] sigmatropic rearrangement to the isothiocyanate. The isothiocyanate is trapped by the solvent to give racemic 0-cthyl-/V-(4-methoxycarbonyl-2-cyclohexcnyl)thiocarbamate in a 66 33 diastereomeric ratio (cisjtram). A Lewis acid catalyzed variant of this tandem reaction showed better diastereoselectivity (90 10)111. 

The position of a trimethylsilyl substituent in phenols 33 determines great yield differences in both thiocarbamate formation and rearrangement [57, 58]. The required TMS-substituted phenols, which were prepared from the respective bromophenols, were tested under standard conditions (Scheme 19). The yield of the rearrangement decreased as the substituent moved from para to ortho. 

The starting thiocarbamates can also be used for selective introduction of further substitution at 2-position via 2-directed metallation [60]. Indeed, s-BuLi in TMEDA selectively furnished the 2-lithiated product, which was reacted with electrophiles to produce the corresponding compounds shown in Scheme 20 [61]. 

The ability of sulfur to stabilize carbanions is exemplified in the following cases. The pentadienyldi-thiocarbamate (144 Scheme 11) can be alkylated at the methylene group to afford the methylated product (145). At 110 C, the dithiocarbamate unit walks its way to the other end of the pentadienyl chain via tandem [3,3] sigmatropic rearrangements. The formation of (14d) is thermodynamically controlled as the more-substituted pentadienyl unit is formed. Dithiocarbamate (146) can be alkylated and eventually transformed into sulfur-free products the sequence giving (148) from (146) is but one of these processes. 

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