Dithio Esters Research Articles

Site‐Specific S‐Allylation of α‐Enolic Dithioesters with Morita‐Baylis‐Hillman Acetates at Room Temperature: Precursor for Thiopyrans

AbstractAn efficient one‐pot allylic alkylation of α‐enolic dithioesters (DTEs) with Morita‐Baylis‐Hillman (MBH) acetates has been devised in ethanol at room temperature. The reaction being site‐selective provided S‐allylated product exclusively with trace amount of C‐allylated one. Remarkably, some of the S‐allylated product undergoes [3,3]‐sigmatropic rearrangement to C‐allylated one under ethanol reflux. The typical feature of this protocol is the isolation of S‐allylated α‐oxoketene dithioacetals, a trisubstituted olefin, which have been further exploited toward the synthesis of thiopyrans.magnified image

ChemInform Abstract: Acid‐Controlled Chemodivergent Synthesis of Three Differently Substituted Quinolines via Site Selective Coupling of ortho‐Aminoaryl Ketones with α‐Enolic Dithioesters.

A straightforward approach for the chemodivergent synthesis of quinolines is described through site-selective coupling of ortho-aminoaryl ketones with α-enolic dithioesters (DTEs) under solvent-free conditions. The operationally and user-simple one-pot methodology is based on the trifunctional nature of DTEs. Both the carbonyl and the thiocarbonyl moiety in α-enolic dithioesters were employed for the efficient construction of three differently substituted quinolines in a chemoselective manner simply by variation of an easy to handle acid catalyst.

Acid‐Controlled Chemodivergent Synthesis of Three Differently Substituted Quinolines via Site Selective Coupling of ortho‐ Aminoaryl Ketones with α‐Enolic Dithioesters

AbstractA straightforward approach for the chemodivergent synthesis of quinolines is described through site‐selective coupling of ortho‐aminoaryl ketones with α‐enolic dithioesters (DTEs) under solvent‐free conditions. The operationally and user‐simple one‐pot methodology is based on the trifunctional nature of DTEs. Both the carbonyl and the thiocarbonyl moiety in α‐enolic dithioesters were employed for the efficient construction of three differently substituted quinolines in a chemoselective manner simply by variation of an easy to handle acid catalyst.magnified image

ChemInform Abstract: New Aspects of Dithio and Thiono Esters.

Abstract The field of dithio and thiono esters is expanding rapidly. Therefore emphasis is layed mainly on results obtained by the research group of the author. In agreement with theoretical considerations thiono esters are always more stable than dithio esters. In the preparation of dithio and thiono esters by thiolysis slightly acidic conditions were found to be essential. The CH-acidity at the α-carbon of dithio and thiono esters with pK values about 12 is comparable to that of classical aCH-acidic compounds such as acetoacetic ester. Dithiono and tetrathio malonates do not show the expected chemistry of malonic esters; the electrophile reacts preferentially at the sulfur atom, α, β-Unsaturated dithio and thiono esters have been prepared by Wittig-Horner reactions, by Peterson synthesis, and by aldol condensations. α, β-Acetylenic dithio and thiono esters were obtained for the first time. In the formation of thiopeptide bonds from α-amino dithio esters the racemization observed seems to be of fundament...

Synergistic Interaction Between ATRP and RAFT: Taking the Best of Each World

This review covers recent developments on the combination of atom transfer radical polymerization (ATRP) and reversible addition–fragmentation chain transfer (RAFT) polymerization to produce well controlled (co)polymers. This review discusses the relative reactivity of the R group in ATRP and RAFT, provides a comparison of dithiocarbamate (DC), trithiocarbonate (TTC), dithioester (DTE), and xanthate versus bromine or chlorine, and an optimization of catalyst/ligand selection. The level of control in iniferter polymerization with DC was greatly improved by the addition of a copper complex. New TTC inifers with bromopropionate and bromoisobutyrate groups have been prepared to conduct, concurrently or sequentially, ATRP from Br-end groups, ATRP from the TTC moiety, and RAFT polymerization from the TTC moiety, depending on the combination of monomer and catalyst employed in the reaction. The use of concurrent ATRP/RAFT (or copper-catalyzed RAFT polymerization or ATRP with dithioester leaving groups), resulted in improved control over the synthesis of homo- and block (co)polymers and allowed preparation of well-defined high-molecular-weight polymers exceeding 1 million. Block copolymers that could not be prepared previously have been synthesized by sequential ATRP and RAFT polymerization using a bromoxanthate inifer. A simple, versatile, and one-step method involving atom-transfer radical addition–fragmentation (ATRAF) for the preparation of various chain transfer agents (including DC, DTE, and xanthate) in high purity is discussed and a one-pot, two-step polymerization starting with a RAFT agent synthesized by ATRAF, followed by polymerization, is demonstrated.

BenzylN′-(2-methoxybenzoyl)hydrazinecarbodithioate

The title dithio ester, C16H16N2O2S2, was synthesized by the reaction of potassium N′-(2-methoxy­benzo­yl)hydra­zine­carbodithio­ate and benzyl chloride in chloro­form. The dihedral angle between the 2-methoxy­phenyl ring and the benzyl ring is 85.06 (2) A. In the crystal structure, intra- and inter­molecular hydrogen bonding stabilizes the mol­ecule and the crystal packing.

Additional Retardation in RAFT Polymerization: Detection of Terminated Intermediate Radicals

AbstractThe reversible addition‐fragmentation chain transfer (RAFT) polymerization of N‐acryloylmorpholine (NAM) is performed using three dithioesters (DT) as chain transfer agents (CTA) that incorporate a morpholine (morpholine‐DT), a biotin (biotin‐DT), or a sugar (sugar‐DT) moiety in the R group. PolyNAM chains of controlled characteristics are synthesized. An unexpected behavior is observed with morpholine‐DT, described as an ‘additional retardation’, which is especially visible when low molar masses are targeted ($\overline M _{\rm n} $ < 5 000 g · mol−1). In that particular case, further investigations using MALDI‐TOF mass spectrometry show the presence of terminated intermediate radicals (IRs), which corroborates the assumption based on a specific protection of IR according to the nature of the α‐chain‐end.magnified image

Structure–reactivity correlations in the aminolysis of aryl dithiomethyl- and dithiophenylacetates with anilines in acetonitrile

The kinetics and mechanism of the anilinolysis (XC6H4NH2) of dithio esters, RC(S)SC6H4Z with R = C2H5 and C6H5CH2 are investigated in acetonitrile at 45.0 °C. By application of various structure–reactivity correlations, selectivity parameters ρX, βX, ρZ, βZ and ρXZ are determined. The reactions are predicted to proceed stepwise with rate-limiting expulsion of the ArS− group. The dithio ester with R = C2H5 exhibits the fastest rate and the largest positive ρXZ value; this is interpreted to result from the strongest electron donating ability of the ethyl group in the intermediate and a crowded tetrahedral intermediate and transition state in which the nucleophile (X) and leaving group (Z) are in close proximity due to the bulky C2H5 group. Much faster rates are observed for the thiocarbonyl (CS) rather than carbonyl (CO) esters in the stepwise nucleophilic substitution reactions, which may be ascribed to the lower π*CS and σ*C–LG levels than those of the corresponding antibonding levels in the carbonyl esters. The normal kinetic isotope effects, kH/kD > 1.0, involving deuterated anilines suggest concurrent proton transfer with the expulsion of the ArS− leaving group in a four-center hydrogen bonded transition state.

Kinetics and mechanism of the aminolysis of aryl propanedithioates in acetonitrile

The kinetics and mechanism of the aminolysis of aryl proanedithioates with benzylamines are investigated in acetonitrile at −35.0 °C. A large magnitude of the Hammett (ρX and ρZ) and Bronsted (βX and βZ) coefficients and exceptionally large cross-interaction constant ρXZ(= 3.5) are consistent with a stepwise mechanism in which leaving group expulsion from an intermediate, T±, is the rate-determining step. The faster rates observed for dithio esters (II) than for thio esters (I), and the validity of the reactivity-selectivity principle (RSP) are also in line with the mechanism proposed. The kH/kD values (= 1.0–1.8) determined with deuterated benzylamines (XC6H4CH2ND2) and the activation parameters, ΔH≠(≃ 8 kcal mol−1) and ΔS≠(= −16 to −23 e.u.), suggest that proton transfer occurs concurrently with leaving group departure in the transition state.

Kinetics and Mechanism of the Aminolysis of Phenyl Dithioacetates in Acetonitrile

The aminolysis reactions of phenyl dithioacetates with anilines (AN), N,N-dimethylanilines (DMA), and benzylamines (BA) in acetonitrile are investigated. The mechanism is relatively simple, involving a zwitterionic tetrahedral intermediate, T±, and is uncomplicated by the fast proton transfer step which may become rate limiting in the aminolysis of thiono and dithio esters and carbonates with poor leaving groups in water. The mechanism changes from rate-limiting expulsion of the leaving group with βX = 0.80−0.86 and βZ = −0.71 to −0.84 for ANs and DMAs to rate-limiting attack by the nucleophile with much smaller magnitudes of βX and βZ for BAs. The relatively large βXZ values for the former series and a smaller βXZ for the latter series support the proposed mechanistic change.

1,3‐Dipole mit zentralem S‐Atom aus der Umsetzung von Aziden mit Thiocarbonyl‐Verbindungen: Eine unerwartete MeS‐Wanderung im Abfangprodukt eines ‘Thiocarbonyl‐aminids’ mit Dithiobenzoesäure‐methylester

1,3‐Dipoles with a Central S‐Atom from the Reaction of Azides and Thiocarbonyl Compounds: An Unexpected MeS Migration in the Trapping Product of a ‘Thiocarbonyl‐aminide’ with Methyl DithiobenzoateReaction of PhN3 with O‐methyl thiobenzoate (11a) and thioacetate (11c) as well as with the dithio esters 11b,d at 80° yields the corresponding imidates and thioimidates 12 (Scheme 3). The formation of 12 is rationalized by a 1,3‐dipolar cycloaddition of the azide and the CS group followed by successive elimination of N2 and S. In the three‐component reaction of 11b, PhN3, and the sterically crowded thioketone 1a, 1,2,4‐trithiolane 13a and 1,4,2‐dithiazolidine 3a are formed in addition to 12b (Scheme 4). The heterocycles 13a and 3a are trapping products of 1a and ‘thiocarbonyl‐thiolate’ 5a and ‘thiocarbonyl‐aminide’ 2a (ArPh), respectively (Scheme 6). These 1,3‐dipoles are formed as reactive intermediates. Surprisingly, in the presence of catalytic amounts of acids, the major product is the (methyldithio)cyclobutyl thioimidate of type 14 (Scheme 5), formed by an acid‐catalyzed MeS migration in dithiazolidine 17. A reaction mechanism is proposed in Scheme 7.

Synthesis of chiral sulfines by oxidation of dithio esters

AbstractThe synthesis of sulfines (thione oxides) (2, 10 and 17) derived from three chiral dithio esters (1, 8 and 16) bearing a hydrogen at the α‐carbon atom is described. The sulfine bearing an amido group at C‐α (2), does not racemize and proved to be stable over a long period. When C‐α in the sulfine (10) bears an acetoxy group the optical activity remained unchanged for a period of two months; after longer storage a rearrangement to a mixture of dithioperoxy ester 12 and S‐methyl ester 11 took place. With an alkyl group at C‐α, the sulfine 17 undergoes a fast racemization and rearranges slowly to a mixture of S‐ethyl ester 14, dithioperoxy ester 18 and S‐vinyl thiosulfinate 19.

High-Performance Raman Spectroscopic System Based on a Single Spectrograph, CCD, Notch Filters, and a Kr+ Laser Ranging from the Near-IR to Near-UV Regions

We describe the performance of a high-throughput system for detecting Raman spectra excited in the range from 320 to 750 nm. The system utilizes notch filters to reject Rayleigh scattering, a single polychromator as the dispersive element, and photon detection via a charge-coupled device. The filters, mirrors, and grating are changed to maximize performance in each excitation region. The excitation source consists of a Kr+ ion laser. Good-quality Raman data are reported for rhodamine 6G at 0.1 mM in methanol with the use of 752.5-nm excitation, and 0.2 mM flavin adenine dinucleotide (FAD) in tris buffer with the use of 647.1-nm excitation. High-quality resonance Raman data for 0.1 mM N-acetyl-glycine ethyl dithio ester in 5% CH3CN/H2O are also reported with the use of 324.0-nm excitation.

The Use of Thiocarbonyl Compounds in Carbon-Carbon Bond Forming Reactions

The behavior of thioaldehydes, thioketones, thiono esterts (O-alkyl thioates) and dithio esters (S-alkyl dithioates) has been reviewed. Specific properties of thiocarbonyl compounds have been shown: Michael addition reaction of enethiolates, thiophilic addition of nucleophiles, easy thio-Claisen rearrangement, [4+2] cycloaddition with dienes and rich dipolarophile chemistry. 1. Introduction 2. Nucleophilic Reactions in Basic Medium 2.1. Generation of Enethiolates 2.2. Aldol Reaction 2.3. Wittig-Horner Reaction 2.4. Michael Addition 2.5. Opening of Epoxides 2.6. Sulfur Alkylation 3. Reactions with Nucleophiles 3.1. Thiophilic Versus Carbophilic Addition of Grignard Reagents and Alkyllithiums 3.2. Unsaturated Thiocarbonyl Compounds as Michael Acceptors 3.3. Claisen Condensation and Other Reactions with Enolates 3.4. Reactions with Sulfur and Phosphorus Ylides 4. Pericyclic Reactions 4.1. [2.3] Sigmatropic Rearrangements 4.2. The Thio-Claisen Rearrangement 4.3. Other [3.3] Sigmatropic Rearrangements 4.4. Diels-Alder Addition Reaction 4.4.1. Thiocarbonyl Compounds as Dienophiles 4.4.2. Thiocarbonyl Compounds as Dienes 4.5. Ene Reaction 4.6. [2+2] Cycloadditions 4.7. Dipolar Cycloadditions 4.7.1. Diazoalkanes and Generation of Thiocarbonyl Ylides 4.7.2. Cycloaddition with Nitrile Oxides, Imines and Sulfides, Nitrones, Nitronates, Azomethine Imines and Ylides 5. Conclusion

Enzyme chemistry of [formula omitted]hemiacetals: Synthesis and characterization of [formula omitted]mandeloylglutathione as an alternate substrate for glyoxalase I

Both the D - and L -forms of S- dithio mandeloylglutathione (1) have been synthesized by a dithio ester-interchange reaction between GSH and S-carboxymethyl ( D , L )- dithio mandelate. Kinetic and product analysis studies indicate that yeast glyoxalase I efficiently catalyzes the stereoselective conversion of D -1 to GSH-phenylglyoxal dithio hemiacetal (2), isolated as a disulfide adduct between 2 and a second molecule of GSH. This observation suggests that dithio ester substrate analogues should be generally useful as mechanistic probes of enzyme catalyzed reactions involving thiohemiacetal intermediates.

On carbon-13 spectra of thio- and dithiocarboxylic acids triorgano group 14 metal esters

The thiocarbonyl carbon chemical shifts of thio- and dithiocarboxyl acid triorgano group 14 metal esters have been studied in comparison with the carbonyl chemical shifts of the corresponding carboxylic and thiocarboxylic acid derivatives. Triorgano group 14 metal groups cause remarkable downfield shifts of the carbonyl and thiocarbonyl carbon chemical shifts in the esters. The thiocarbonyl carbon chemical shifts of the dithio esters ( i-C 3H 7CS 2EMe 3, E = group 14 element) are correlated linearly with the Allred-Rochow electronegativity of the metals, and with their ππ* transition energies except for the silyl esters. The 13CO chemical shifts of trimethyltin isobutyrate appear at the lowest field in the carboxylic acid triorgano group 14 metal esters (RCOOER′ 3, E = group 14 metal). The unusual downfield shifts reflect the polymetric structure of the tin esters. The empirical equation (δ(CS) = 1.45 δ(CO)−46.5 ppm) predicting 13CO and 13CS chemical shifts, which has been proposed by Kolinowski and Kessler, can not be applied for these triorgano group 14 metal esters and ortho substituted benzoates and thio- and dithiobenzoates.

Dithio‐ und Thionester, 50. α,β‐Acetylenische Thioamide, Dithioester und Thionester

Dithio and Thiono Esters, 50. – α,β‐Acetylenic Thioamides, Dithio Esters, and Thiono Estersα,β‐Acetylenic amides 5 and thioamides 7 have been obtained by a palladium‐catalysed condensation of the terminal acetylenes 3 with N,N‐dimethylcarbamoyl chloride (4) or ‐thiocarbamoyl chloride (6). Sulfhydrolysis of the α,β‐acetylenic thioamidium salts 19 or amidium salts 21 leads to the formation of the α,β‐acetylenic dithio esters 22 or thiono esters 23. Both types may also be prepared by a palladium‐catalysed condensation of the terminal acetylenes 3 with methyl carbonodithiochloridate (25) or O‐methyl carbonothiochloridate (26). The thiono esters 23 are also accessible from 26 and the alkyne Grignard reagents 29. Finally, reactions of 22 and 23 with amines, thioles, alkylating agents, and cyclopentadiene are described.

New Aspects of Dithio and Thiono Esters

Abstract The field of dithio and thiono esters is expanding rapidly. Therefore emphasis is layed mainly on results obtained by the research group of the author. In agreement with theoretical considerations thiono esters are always more stable than dithio esters. In the preparation of dithio and thiono esters by thiolysis slightly acidic conditions were found to be essential. The CH-acidity at the α-carbon of dithio and thiono esters with pK values about 12 is comparable to that of classical aCH-acidic compounds such as acetoacetic ester. Dithiono and tetrathio malonates do not show the expected chemistry of malonic esters; the electrophile reacts preferentially at the sulfur atom, α, β-Unsaturated dithio and thiono esters have been prepared by Wittig-Horner reactions, by Peterson synthesis, and by aldol condensations. α, β-Acetylenic dithio and thiono esters were obtained for the first time. In the formation of thiopeptide bonds from α-amino dithio esters the racemization observed seems to be of fundamental importance. Dianions of dithio acids were found to condense with different electrophiles.

Dithiazoles and related compounds. Part 3. Preparation of 5H-1,4,2-dithiazoles via 1,3-dipolar cycloadditions between nitrile sulphides and thiocarbonyl compounds, and some conversions into 3,5-diaryl-1,4,2-dithiazolium salts

Thermolysis of 1,3,4 -oxathiazol-2-ones 3 in the presence of thiocarbonyl compounds gives modest to good yields of the little-known 5H-1,4,2-dithiazoles 1, the reaction being successful with diaryl, aryl alkyl and dialkyl ketones, and thiono esters, but failing with dithio esters and tertiary thioamides. The influence of substituents is discussed. Solvolysis of 5-ethoxy-5H-1,4,2-dithiazoles, derived from thiono esters, with perchloric acid in acetic anhydride gives high yields of 3,5-diaryl-1,4,2-dithiazolium salts 9.

ChemInform Abstract: New Thioacylating Reagents: 1‐Methyl‐2‐thioacylthiopyridinium Salts (III).

AbstractThe dithio ester salts (III) (recently (1986) suggested to be intermediates in the preparation of sulfides) are now isolated by the use of CHCl3/MeOH as the solvent.