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While thiophosgene finds widespread usage on a multi-ton scale, its fluorinated counterpart S=CF2 is essentially unexplored in synthesis. Using experimental reactivity tests, ReactIR and computational techniques, we herein showcase that the solid (Me4 N)SCF3 functions as a safe reservoir for S=CF2 . A key feature is that the reactive electrophile is not simply released over time, but instead is liberated under activation with a protic nucleophile. The reactivity of S=CF2 is mild, allowing large-scale and late-stage synthetic applications without special reaction control. The mechanism was fully elucidated, including a rationalization of the role of the Me4 N cation and the origins of selectivity.

Five new nonsymmetric BODIPY dyes based on the Biellmann methodology [NSBBs (nonsymmetrical Biellmann BODIPYs)] were prepared by condensation of pairs of different pyrroles with thiophosgene. Treatment of the resulting thioketones with MeI and BF3·Et2O/TEA yielded a wide range of products in a simple manner, with selective alkylation of each pyrrole of the indacene core and with controlled functionalization at the meso position. A comprehensive combined photophysical and computational study has been conducted to determine the impact of the alkylation pattern, as well as the role of the conformational freedom and electron coupling of 8-phenyl and 8-methylthio groups on the spectroscopic signatures of BODIPYs. The results and conclusions reached are compared with those for previously reported related analogues. We intend to provide key structural guidelines with regard to the factors that trigger the fluorescence responses and spectral shifts of multifunctional fluorophores of this family.

2-Thioxo-1,3-oxazepine-4,7-dione compounds were obtained via triethylamine-catalyzed condensation of maleamic acids with thiophosgene under anhydrous conditions. This method features relatively a simple methodology, use of inexpensive reagents, convenient operating conditions and high yields.

It has been shown that certain N-aryltrichoromethanesulfenamides Cl3C−S−NHAr can be dehydrochlorinated to form red-colored thiocarbonyl S-imides CCl2=S=NAr which dimerize spontaneously. The dimers ...

A novel, high-yielding, one-step synthesis of 2-chloroquinazolin-4-ols and analogous bicycles from 2-aminoamides using thiophosgene is described. The scope of the reaction includes aminothioamides, amino acids, and fused heterocycle derivatives, furnishing quinazolines, oxazinones, and substituted fused pyrimidine bicycles, respectively. On the basis of observed results with substituted analogues, a mechanism for this transformation is thought to occur via an isothiocyanate intermediate followed by an unexpected chemoselective reaction of thiophosgene on the thiol intermediate.

A sequential one-pot synthesis of N-sulfonylcyclothioureas from N-monosulfonyl diamines, CS2 and chloroacetic acid at room temperature in water is described. In the absence of highly toxic thiophosgene and organic solvents, this method is environmentally benign. Simple reaction conditions, easy purification of the products, good yields and thioglycolic acid as the useful byproduct are also important attributes of this methodology. The plausible mechanism including tandem reactions is proposed.

A calculation of the rate of ISC (intersystem crossing) relaxation at 0 K requires a knowledge of the spin–orbit coupling and the vibrational overlap integrals (Franck-Condon factors) between the T1 and S0 states. At elevated temperatures, the population of the rotational states needs to be taken into account through the overlap of the rotational wavefunctions between the interacting T1/S0 electronic states. Here, we discuss the effect of the ISC singlet–triplet selection rules on the number and magnitude of the rotational overlap factors for the J = 0, 5, and 10 rotational levels of thiophosgene, Cl2CS. Of equal importance is the influence of the spin–spin and spin-rotation coupling on the rotational fragmentation factors and the ISC survival probability. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011

The amorphous, brownish black substance obtained by Dewar and Jones from nickel carbonyl and thiophosgene, has not the composition (CS)x but contains organically combined chlorine. The reaction has been carried out in various solvents; the amorphous reaction products have been completely analysed and it appears that the solid adsorbs the solvent, which cannot be completely removed. The C: S ratio in these products therefore varies from 1: 0.8 to 1: 0.9. The reaction was also carried out in the vapour phase. The amorphous product so obtained also contained organically combined chlorine while the C:S ratio was 1: 1.03 in this case. Thus the product produced from nickel carbonyl and thiophosgene is not a polymeric form of carbon monosulphide.

Isothiocyanates having the NCS-group bound directly to the CC-bond — the vinyl isothiocyanates — are of high synthetic interest because this type of heterodienes is a suitable precursor for heterocyclic compounds and derivatives of thiocarbamic acid. They cannot be prepared by standard methods. In this review we report 1) the synthesis of vinyl isothiocyanates by the reaction of nitrogen compounds with thiophosgene and other sulphur compounds, SNV-reactions, elimination of HX, addition of HSCN to alkynes, cleavage of heterocycles and by miscellaneous methods 2) structure and reactivity of the vinyl isothiocyanates and 3) the reactions of these conjugated mustard oils with numerous nucleophiles and their behaviour as heterocumulenes in cycloaddition reactions.

Both alkyl and aryl chlorothioformates could readily be obtained from the corresponding alcohols and thiophosgene. These families of compounds were treated with BrF3 to form the corresponding alkyl and aryl chlorodifluoromethyl ethers in 60–85 % yields. The method is suitable for constructing a variety of aliphatic as well as electron-deficient aromatic chlorodifluoromethyl ethers. The reactions proceed under mild conditions and short reaction times. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Poly(pyridylureas) and poly(pyridylthioureas) were synthesized by reacting 2,6-diaminopyridine with phosgene and thiophosgene, respectively, using THF and pyridine as solvent. The synthesized polymers were characterized by IR-spectroscopy, elemental analysis, and X-ray photoelectron spectroscopy. Thermal stability of the polymers was determined by thermal degradation between 35°C and 700°C. The 50% weight loss of polypyridylureas was above 400°C while for the polypyridylthioureas it was above 450°C. Undoped poly(pyridylureas) and poly(pyridylthioureas) behave as semiconductors, σ = 10−9 (Ω cm)−1. After doping with I2 and SbF5, the electrical conductivity increases several orders of magnitude, σ = 10−7(Ω cm)−1. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007

2-Thioxo-1,3-oxazepine-4,7-dione compounds were obtained via triethylamine-catalyzed condensation of maleamic acids with thiophosgene under anhydrous conditions. This method features relatively a simple methodology, use of inexpensive reagents, convenient operating conditions and high yields.

Isothiocyanates have gained considerable attention for their role as potent chemopreventive agents. Sulforaphane, 1a (SFN), a naturally occurring isothiocyanate, was isotopically labelled in five steps starting from 3-(methylthio)-1-propanol (2). Reacting 2 with tosyl chloride in the presence of Et3N yielded the tosylate 3. Gently refluxing 3 with K14CN in DMF gave the nitrile 4b. Reduction to the amine 5b was achieved using BH3-THF. Oxidation with 30% hydrogen peroxide followed by treatment with thiophosgene yielded (±)[1-14C]SFN, 1b. The overall radiochemical yield was 4.4% based on the starting K14CN. Copyright © 2003 John Wiley & Sons, Ltd.

In this study, a protocol for the synthesis of symmetrical diaryl trithiocarbonates through the one-pot copper-catalyzed coupling reaction of sodium sulfide, carbon disulfide, and aryl compounds in DMF solution is presented. This method allows the synthesis of symmetrical diaryl trithiocarbonates without the use of highly toxic thiophosgene, and also, commercially available aryl halides were used instead of less available, toxic thiols.

A procedure for the synthesis of benzo[e][1,3]thiazine-2,4-diones from benzamides by directed lithiation and sequential treatment with sulfur and phosgene is reported. Use of thiophosgene afforded 2-thioxo-2,3-dihydro-benzo[e][1,3] thiazin-4-ones. Application of this methodology to benzenesulfonamides afforded the previously unknown 1,1-dioxo-1,2-dihydro-1,4-dithia-2-aza-naphthalen-3-one ring system with phosgene and the 1,2-dioxo-2-phenyl-2,3-dihydrobenzo[e][1,4,2]dithiazine-3-one ring system with thiophosgene. Use of selenium in place of sulfur afforded the novel analogous selenium heterocycles, however in the case of benzamides the use of selenium and phosgene afforded benzo[d]isoselenazol-3-ones unexpectedly.

Propargyl isothiocyanates 3 and buta-2,3-dienyl isothiocyanates 20 were prepared conventionally from amines and thiophosgene, or by a new, one-pot procedure using nucleophilic substitution to generate azides, which in turn served as the starting materials for a Staudinger reaction, followed by treatment of the resulting iminophosphoranes or iminophosphates with CS2. Equilibration, through a [3,3] sigmatropic rearrangement, of 3 and the allenyl thiocyanates 4 was established by flash vacuum pyrolysis or by thermolysis in solution. Even the reversible isomerization of the parent compounds 3f and 4f favors the allenyl thiocyanate. In the case of 20, an irreversible rearrangement reaction gave high yields of 2-thiocyanatobuta-1,3-dienes 21. A sequence of two [3,3] migration steps transformed 1,4-diisothiocyanatobut-2-ynes 3m and 3n into 2,3-dithiocyanatobuta-1,3-dienes 21m and 22, respectively. These reactions demonstrate that the [3,3] sigmatropic rearrangement of mustard oils, to afford high yields of thiocyanates bearing the thermodynamically less stable functional group, is possible if the conversion gives rise to a more stable carbon skeleton. The equilibration of 1-thiocyanatopent-2-en-4-ynes 12 and 1-thiocyanatopenta-1,2,4-trienes 14 could be explained by tandem [3,3]−[3,3] sigmatropic rearrangements through short lived 3-isothiocyanatopent-1-en-4-ynes 13. Thiocyanato-substituted vinylallenes 4k and 14 tended to electrocyclize to give cyclobutenes 7 and 15, respectively. Thiocyanates 21a, 21b, 21m and 14a, which exhibit a buta-1,3-diene structure, could be used in Diels−Alder reactions to afford the cycloadducts 25a, 25b, 26a, 26m, 28m, 29m, and 30.

Ethyl vis- and trans-2-isothiocyanato-1-cyclopentanecarboxylates 2 and 7 were prepared by the reaction of the corresponding alicyclic ethyl 2-amino-1-carboxylates and thiophosgene. The cis-isothiocyanato compound 2 underwent ring closure with amines in one or two steps, resulting in 3-substituted-cis-2-thioxocyclopenta[d]pyrimidin-4-ones 3a-g. The trans isomer 7 failed to cyclize, but gave carboxamide 8a,b or thiourea ester derivatives 9a,b.

2-Phenyl-[1-14C]-ethyl isothiocyanate and S-(N-phenyl-[1-14C]-ethylthiocarbamoyl)cysteine were synthesised from 2-phenyl-[1-14C]-ethylamine. Phenylethylamine was reacted with thiophosgene to make phenethyl isothiocyanate (yield: 36%, based on phenylethylamine). Phenethyl isothiocyanate was converted to the cysteine conjugate S-(N-phenethylthiocarbamoyl)cysteine by reaction with cysteine and crystallisation (yield: 86%, based on phenethyl isothiocyanate). The compounds have been used to study the cellular and subcellular labelling of tumour cells during the induction of apoptosis in human tumour cells by phenethyl isothiocyanate and S-(N-phenethylthiocarbamoyl)cysteine in vitro. Copyright © 1999 John Wiley & Sons, Ltd.

Stable Tetraazafulvalenes – Syntheses and Chemistry The syntheses, properties and reactions are described for 1,3,6,7-tetrakis[arylamino]-1,4,5,8-tetraazafulvalenes and their vinylogous derivatives. First, the acylation of form- as well as acetamidine with bis-imidoylchlorides derived from oxalic acid 6 formed reactive cyclic intermediates which dimerized to tetraazafulvalenes 12 or bisvinylogous tetraazafulvalenes 14. Based on, a further synthesis was found using a cycloacylation reaction of amidines with imidoylchlorides 6 followed by prototropic migration of α-hydrogen. Thus, the vinylogous compound 15 and the phenylogous derivatives 16, 17 could be isolated in moderate up to good yields. Besides amidines, other derivatives of carboxylic acids as amides or thioamides could be transformed into corresponding tetraazafulvalenes 18–20. Due to their vicinal amino groups, alkylation and acylation reactions were studied. For example, the reaction with orthoformates yielded the ring fused products 24a,b which may be starting material for carbenes just as the cyclization product with thiophosgene 27. Treatment of tetraazafulvalenes with anhydrous iron-II salts or molybdenum hexacarbonyl yielded the deeply colored metal diazadiene complexes 33 and 34. Finally, reduction using metallic lithium and subsequent alkylation constitutes a convenient synthetic entry to heterocyclic analogues of stilbene 37.

Diels–Alder reactions of various thiocarbonyl S-oxides and thiocarbonyl S,S-dioxides with buta-1,3-diene were studied by semiempirical AM1 and PM3 methods. Calculations show that the reactions of such unsymmetrical heterodienophiles pass through asynchronous transition states (TSs) with C=S π* involved in the reaction. Calculated activation energies indicate that the reactivity of these heterodienophiles, viz. R2C=S, R2C=SO and R2C=SO2, decrease gradually with successive addition of oxygen atoms to the thiocarbonyl sulfur. This is in good agreement with the experimental observations. The predictions based on LUMO and deformation energies show that the above reactivity trend corresponds to a gradual destabilization of LUMO of the dienophile and increase in deformation energy of both diene and dienophile with increase in the number of oxygen atoms around sulfur. Thiophosgene and their S-oxides in Diels–Alder reactions are found to be less reactive than the parent analogues. Monosubstituted (Z/E)-sulfines react with buta-1,3-diene to form cis and trans products through closely lying TSs. Calculations predict that (E)-sulfine has a higher reactivity than the Z-isomer, in reasonable agreement with experimental results. © 1997 John Wiley & Sons, Ltd.

Treatment of Cp2Ti(CO)2 (3) with the di- and polysulfanes 1,2,4-(CH2)2S3, C4S6 (9), C,7H10S3 (11), 1,2,4,6-(CH2)3S4 (16), C6H10S6(19), and S6 affords the titanocene chelate complexes Cp2TiS3(CH2)2 (8), (Cp2Ti)2C4S6 (10), Cp2TiS3C7H10 (13), Cp2TiS2C7H10 (14), Cp2TiS4(CH2)3 (17), Cp,2TiS6C6H6H10 (20), and Cp2TiS8 (23). 14 is also obtained from Cp2TiCl2 (1) and the geminal dithiol of norbornene. The analogous reaction with the dithiol of dicyclopentadiene yields Cp2TiS2C10H12 (15). In ligand transfer reactions, 8 reacts with SCl2 to give 1,2,3,5-tetrathiane (25), 10 provides 9 on reaction with Cl2, 13 when treated with S2Cl2 affords C7H10S5 (12), 15 reacts with S2Cl2Cl2 to give C10H12S4. 17 and SCl2 yield 1,2,3,5,7-pentathiepane (18), 20 is converted to C6H10S7 (22) on reaction with SCl2, and 23 yields S10 and 1,2,-C6H4(SCl)2, respectively. With phosgene, thiophosgene, and thionyl chloride, compound 15 yields the corresponding dithiocarbonate 26, the trithiocarbonate 27 and the trisulfane 2-oxide 28. The structure of 27 was determined by X-ray crystallography.

A new enantioselective (80% ee) synthesis of (R)-sulforaphane and its epimer (S)-sulforaphane is described, which makes use of the pseudo-tetrahedral complex fragment [CpRu-(CHIRAPHOS)]+ as a chiral auxiliary. Reaction of the chloride complexes [CpRu(L–L)Cl] [L–L = 1,-bis(diphenylphosphino)ethane (dppe), (2S,3S)-and (2R,3R)-bis(diphenylphosphino)-butane ((S,S)- and (R, R)-CHIRAPHOS, respectively)] with phthalimidobutyl methyl sulfide gives the thioether complexes [CpRu(L–L)(MeSC4H8NPhth)]PF6. Oxygen transfer from dimethyldioxirane (DMD) produces the corresponding sulfoxide complexes in high yield and high diastereoselectivity. Cleavage of the phthaloyl group with aqueous hydrazine and subsequent reaction with thiophosgene yields the sulforaphane complexes [CpRu(L–L)(MeS(O)C4H8NCS)]PF6. Treatment of these with sodium iodide finally liberates the sulforaphane without noticeable racemization.

Cycloacylation of formamidine with bisimidoyl chlorides of oxalic acid yields the new 1,4,5,8-tetraazafulvalenes 4 via dimerization of carbenoid intermediates. The high symmetry of the stable heterofulvalenes as well as their dye character is confirmed by NMR and UV/Vis spectral data. Whereas methylation of these substrates leads to a mixture of diastereomeric tetramethyl derivatives 9a, b, cyclization with thiophosgene or triethyl orthoformate gives mainly the fused-ring derivatives of 2H-imidazole 10 and 12a, b, respectively. In the case of 12a, the X-ray crystal structure reveals the approximately ideal planarity of the central tetraazafulvalene subunit.

The title compounds (III) are formed by reaction of thiophosgene with carbonotrithioates or O-ethyldithiocarbonates (I).

This method allows the synthesis of symmetrical diaryl trithiocarbonates without the use of highly toxic thiophosgene.

A general synthetic approach for the synthesis of 15N- and 17O-doubly labelled pyrimidine nucleosides is described. The 15N isotopes in uridine and the 17O isotope in the urea-derived carbonyl group of uridine and cytidine originate from (15N2)[17O]urea (5) which was synthesized from 15NH4Cl, thiophosgene (1), and H2[17O]. The third 15N isotope of cytidine in 4-position stems from the substitution of the 1,2,4-triazole moiety of (15N2)[O2-17O]uridine derivative 8a/b with 15NH4OH. Hydrolysis of the same key intermediate 8a/b with Na[17O]H/H2[17O] introduced the second 17O isotope into the 4-position of uridine. The 15N- and 17O-NMR spectra of the target compounds 12 and 14 in phosphate-buffered H2O serve as references for heteronuclear NMR spectra of labelled RNA fragments.

In this work, we described the synthesis of 3-isothiocyanatoselenophenes starting from 3-aminoselenophenes (using thiophosgene). Those compounds were then converted to the corresponding thioureas in the presence of ammonium hydroxide. Cyclization in 2-aminoselenolo[3,2-d]thiazoles was achieved using DDQ. 2-Aminothieno[3,2-d]thiazoles were obtained from 3-isothiocyanatothiophenes using the same pathway.

The reaction is conducted under environmentally benign conditions, avoiding heating, thiophosgene, and organic solvents.

Reaction of amine ester hydrochlorides with phosgene or thiophosgene generates the corresponding isocyanates or isothiocyanates.

Thiation of N-(1-tert-butyl-3-methylpyrazol-5-yl)carboxamides 2 with the Lawesson reagent afforded the corresponding thiocarboxamides 3. Heating of 3 in formic acid gave the N-dealkylated thiocarboxamides 4 which were cyclized into 4H-pyrazolo[1,5-c][1,3,5]thiadiazine-4-thiones 5 by treatment with thiophosgene.

The reactions of 1-alkylamino-1-alkylthio-3-phenylpropene-3-thiones 3 with thiophosgene and phosgene in toluene, followed by treatment of the reaction mixture with triethylamine gave 3-alkyl-2,3-dihydro-4-oxo-6-phenyl-2-thioxo- 4, 3-alkyl-2,3-dihydro-2,4-dioxo-6-phenyl-4H-1,3-thiazines 5, respectively in good to excellent yields. Similarly treatment of compounds 3 with N-arylimidoyl dichloride in benzene at room temperature gave 3-alkyl-2-arylimino-2,3-dihydro-4-oxo-6-phenyl-4H-1,3-thiazines 6 in excellent yields. The reactions of compounds 3 with oxalyl chloride in toluene gave also 5 in good yields.

Treatment of catechols with thiophosgene provide the corresponding thiodioxoles which upon treatment with bromine trifluoride produce potentially biologically important difluoroaryldioxoles in good to very good yields.

Diaminobipyridines such as (I) and (IV) are prepared by known three-step sequence and converted into the corresponding diisothiocyanato derivatives upon treatment with thiophosgene.

Die Sulfeniumsalze Cl2CSCl+ AsF6− und Cl2CSBr+ AsF6− werden aus Thiophosgen Cl2CS durch oxidative Halogenierung mit X2/AsF5 (X = Cl, Br) bei 195 K dargestellt und schwingungs- sowie NMR-spektroskopisch charakterisiert. The Synthesis of the Dichloromethylene-halogenosulfenium Salts Cl2CSCl+ AsF6− and Cl2CSBr+ AsF6− The sulfenium salts Cl2CSCl+ AsF6− and Cl2CSBr+ AsF6− are synthesized by oxidative halogenation of thiophosgene, Cl2CS with X2/AsF5 (X = Cl, Br) at 195 K and are characterized by vibrational as well as NMR spectroscopy.

The title compounds (VI) (15 examples) are obtained starting from easily available materials without using the highly toxic thiophosgene.

Colchiceinamide on reaction with phosgene and thiophosgene in the presence of triethylamine afforded tetracyclic compounds:benzo[9,10]heptaleno[4,3-d]oxazolones , -oxazolethiones . Treatment of the resulting tetracyclic oxazolethione with sodium hydroxide afforded tetracyclic thiazolone . All three tetracyclic compounds had very high negative specific rotations, but none of them inhibited tubulin polymerization in vitro.

The asymmetric synthesis of a tetrasubstituted bicyclic guanidine 1 is described. This salt may serve as an oxoanionbinding modul in open-chain artificial receptors. The synthetic key step involves asymmetric alkylation of a Schollkopf bislactim ether 8a/b to produce after protection/deprotection steps a chiral open-chain triamine 13 which can be cyclized by thiophosgene as a C 1 -building block to yield the target structure 1. The diastereoselectivity (%de) and enantioselectivity (%ee) of the synthetic pathway exceed 94%

The absorption, emission, and excitation spectra and emission lifetimes of thiophosgene, Cl 2 CS, in its S 1 and T 1 states have been measured as a function of concentration in a perfluoroalkane solvent at room temperature. Significant dimerization occurs in solution at concentration >10 -4 M, and this must be taken into account when interpreting the spectra. Fluorescence from the monomer in its first excited singlet state is observed (O f 0 =5.5×10 -6 ) and constitutes the short-lived component (τ=40 ps) of a biexponential emission decay

The reaction of aldose oligosaccharides with aqueous ammonium hydrogencarbonate was revised and optimized for gram scale preparation of glycosylamines, using lactose, cellobiose, maltose, and melibiose as model compounds. The unprotected glycosylamines 1b-4b were transformed into the corresponding hepta-O-acetyl hydrochlorides 1e-4e via diethyl N-glycosylaminomethylenemalonates (1c-4c and 1d-4d). Reaction of le-3e with thiophosgene in a three-phased system led to the target hepta-O-acetylglycosyl isothiocyanates lf-3f in excellent yields. Under the same conditions, the melibiosyl derivative 4e underwent partial hydrolysis to give a mixture of melibiosyl isothiocyanate 4f and the reducing sugar derivative 4h. Treatment of 1f-4f with ammonia resulted in the quantitative formation of N-glycosylthioureas (1g-4g).

Thiation of N-(1-tert-butyl-3-methylpyrazol-5-yl)carboxamides 2 with the Lawesson reagent afforded the corresponding thiocarboxamides 3. Heating of 3 in formic acid gave the N-dealkylated thiocarboxamides 4 which were cyclized into 4H-pyrazolo[1,5-c][1,3,5]thiadiazine-4-thiones 5 by treatment with thiophosgene.

The reactions of 1-alkylamino-1-alkylthio-3-phenylpropene-3-thiones 3 with thiophosgene and phosgene in toluene, followed by treatment of the reaction mixture with triethylamine gave 3-alkyl-2,3-dihydro-4-oxo-6-phenyl-2-thioxo- 4, 3-alkyl-2,3-dihydro-2,4-dioxo-6-phenyl-4H-1,3-thiazines 5, respectively in good to excellent yields. Similarly treatment of compounds 3 with N-arylimidoyl dichloride in benzene at room temperature gave 3-alkyl-2-arylimino-2,3-dihydro-4-oxo-6-phenyl-4H-1,3-thiazines 6 in excellent yields. The reactions of compounds 3 with oxalyl chloride in toluene gave also 5 in good yields.

Methyl 2-deoxy-3,4-0-thiocarbonyl-beta-D-ribopyranoside was converted into the thione carbonate by reaction with thiophosgene. Bromide ion-catalyzed 0-S rearrangement produced methyl 2-deoxy-3-0,4-S-carbonyl-4-thio-beta-D-ribopyranoside (3a) and the 3-0,4-S isomer 3b. The carbonates were cleaved with ammonia and the 3-0,4-S pyranoside sugar coupled with bis(trimethylsilyl)-5-ethyluracil using trimethylsilyl triflate to provide the antiherpes agent 2'-deoxy-5-ethyl-4'-thiouridine 9. The reaction proceeded via in, situ pyranoside rearrangement-of the sugar and subsequent coupling. The pyranoside sugar could also be converted to the furanoside form with Dowex H+ acid resin and coupled in conventional fashion to give the nucleoside. Coupling of methyl 4-0-carbamoyl-2-deoxy-3-thio-beta-D-ribopyranoside (4b) with the bis(trimethylsilyl)-5-ethyluracil gave 1-[2-[2-(hydroxymethyl)thiiran-1-yl]-1-methoxyethyl]-5-ethyluracil.

Treatment of 5-(arylimino)-4-(dialkylamino)-5H-1,2,3-dithiazoles (2) with NaOH in aqueous EtOH at room temperature gave N′-arylthiocarbamoyl-N,N-dialkylamidines (3) in good to excellent yields. The reaction of 3 with sulfur monochloride, thiophosgene, thionyl chloride, sulfuryl chloride, N-phenylimidoyl dichloride, and phthaloyl chloride in CH2Cl2 gave 2, 5-(arylimino)-4-(dialkylamino)-Δ3-thiazoline-2-thiones (5), 5-(arylimino)-4-(dialkylamino)-5H-2-oxo-1,2,3-dithiazoles (6), 5-(arylimino)-4-(dialkylamino)-5H-2,2-dioxo-1,2,3-dithiazoles (7), 5-(arylimino)-4-(dialkylamino)-2-(phenylimino)-Δ3-thiazolines (8), and 3-(arylimino)-4-(dialkylamino)-2,5-benzothiazocine-1,6-diones (10) as major products, respectively.

The trifluoromethanethiolate anion may be generated in situ by the reaction of thiophosgene with potassium fluoride in acetonitrile. This system is used to prepare trifluoromethyl aryl sulfides from activated fluoro- and chloroaromatic substrates via nucleophilic substitution.

Methyl 3-aminocrotonate 7 reacts with 4,5-dichloro-1,2,3-dithiazolium chloride 1 at room temperature to give methyl 5-cyano-3-methylisothiazole-4-carboxylate 9 in high yield (78%) (Schemes 1 and 2). This reaction is formally related to Woodward’s synthesis of methyl 3-methylisothiazole-4-carboxylate 24 from the same enamine and thiophosgene (Scheme 7). 3-Aminocrotononitrile 10 is similarly converted into 4,5-dicyano-3-methylisothiazole 12 but the yield is much reduced (to 40%) since the reaction is more complex (Scheme 3) giving 2,3,5-tricyano-4,6-dimethylpyridine 14 (20%), in a new pyridine ring construction, and three other minor products. All the products can be accounted for by reasonable mechanisms (Schemes 4, 5 and 6). One of the minor products, ketone 13, has been synthesized from the enolate anion 21 and the reagent 1, and the analogous ketones 23 have been readily prepared in high yield from the active methylene compounds 22 and reagent 1.

Functionalized alkynes are oxidized to the corresponding α-diketones with catalytic RuO4 and NaIO4. Treatment of these diones with metal acetylenides then gives mixtures of erythro- and threo-1,5-hexadiyne-3,4-diols with good erythro-selectivity. Reaction of the erythro-diols with thiophosgene in the presence of n-BuLi or KH as base results in the formation of the corresponding cyclic thionocarbonates in moderate to good yields. Reaction of the cyclic thionocarbonates with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine at 40 oC results in the formation of enediynes substituted at the 3- and 4-positions. As anticipated fom the mechanism of the pericyclic syn-elimination, the erythro-thionocarbonates provide pure Z-enediynes.