Thiono Esters Research Articles

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...

Nonpolar and Short Side Chain Groups at C-11β of Estradiol Result in Antiestrogens

We have previously found that esters of 11beta-estradiol carboxylates are transformed from an estrogen into an antiestrogen when the 11beta-side chain is increased in length from four to five non-hydrogen atoms (n > or = 5). To understand the structural requirements for this transformation and obtain metabolically stable analogues that are not susceptible to esterase cleavage, we have synthesized other compounds having an 11beta-side chain composed of other functional groups: ketones, amides, ethers, and thiono esters. With the exception of amides, which bind poorly to the estrogen receptor (ER), all of these compounds exhibit antiestrogenic action when the side chain length is n > or = 5. Ethers (n > or = 5), studied in more detail, inhibit the action of estradiol with either ERalpha or ERbeta. In rat uteri they are estrogen antagonists/weak agonists and decrease the concentration of cholesterol in blood (an hepatic estrogenic action). Thus, these short chain and nonpolar 11beta-analogues of estradiol have tissue specific antiestrogenic/estrogenic actions, characteristics of selective estrogen receptor modulators.

Effect of changing electrophilic center from C=O to C=S on rates and mechanism: pyridinolyses of O-2,4-dinitrophenyl thionobenzoate and its oxygen analogue.

Second-order rate constants have been measured spectrophotometrically for the reactions of O-2,4-dinitrophenyl thionobenzoate (1) and 2,4-dinitrophenyl benzoate (2) with a series of substituted pyridines in 80 mol % H(2)O/20 mol % DMSO at 25.0 +/- 0.1 degrees C. The Brønsted-type plots obtained are nonlinear with beta(1) = 0.26, beta(2) = 1.07, and pK(a) degrees = 7.5 for the reactions of 1 and beta(1) = 0.40, beta(2) = 0.90, and pK(a) degrees = 9.5 for the reactions of 2, suggesting that the pyridinolyses of 1 and 2 proceed through a zwiterionic tetrahedral intermediate T(+/-) with a change in the rate-determining step at pK(a) degrees = 7.5 and 9.5, respectively. The thiono ester 1 is more reactive than its oxygen analogue 2 except for the reaction with the strongest basic pyridine studied (pK(a) = 11.30). The k(1) value is larger for the reactions of 1 than for those of 2 in the low pK(a) region, but the difference in the k(1) value becomes negligible with increasing the basicity of pyridines. On the other hand, 1 exhibits slightly larger k(2)/k(-1) ratio than 2 in the low pK(a) region but the difference in the k(2)/k(-1) ratio becomes more significant with increasing the basicity of pyridines. Pyridines are more reactive than alicyclic secondary amines of similar basicity toward 2 in the pK(a) above ca. 7.2 but less reactive in the pK(a) below ca. 7.2. The k(1) value is slightly larger, but the k(2)/k(-1) ratio is much smaller for the reactions of 2 with pyridines than with isobasic secondary amines in the low pK(a) region, which is responsible for the fact that the weakly basic pyridines are less reactive than isobasic secondary amines.

Efficient and Convenient Deprotection of Thiocarbonyl to Carbonyl Compounds Using 3‐Carboxypyridinium and 2,2′‐Bipyridinium Chlorochromates in Solution, Dry Media, and under Microwave Irradiation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Efficient and Convenient Deprotection of Thiocarbonyl to Carbonyl Compounds Using 3-Carboxypyridinium and 2,2'-Bipyridinium Chlorochromates in Solution, Dry Media, and under Microwave Irradiation

A synthetic utility of 3-carboxypyridinium (CPCC) and 2,2′-bipyridinium (BPCC) chlorochromates in deprotection reactions is reported. Different types of thioamides, thioureas, thiono esters, and thioketones are deprotected to their corresponding carbonyl compounds with these reagents in good to excellent yields. The reactions were carried out in solution, under solvent-free conditions, and under microwave irradiation. The results show that with both reagents the rates of the reactions and the yields are usually highest under microwave irradiation.

Convenient Transformation of Thiocarbonyl to Carbonyl Group Using Benzyltriphenylphosphonium and n‐Butyltriphenylphosphonium Peroxodisulfates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Convenient Transformation of Thiocarbonyl to Carbonyl Group Using Benzyltriphenylphosphonium and n-Butyltriphenylphosphonium Peroxodisulfates

Benzyltriphenylphosphonium and n-butyltriphenylphosphonium peroxodisulfates are stable and easily prepared oxidising agents. These reagents are able to convert different thioamides and thioureas to their oxygen analogues in good to excellent yields. Thiono esters are also transformed to esters in high yields. Thioketones such as thiobenzophenone and thiofluorenone are converted to their ketones in high yields while, 4-nitrothiobenzophenone, 2-aminothiobenzophenone and 4-chlorothiobenzophenone remained intact in the reaction mixture.

Bismuth(III) Nitrate Pentahydrate: A Convenient and Selective Reagent for Conversion of Thiocarbonyls to Their Carbonyl Compounds.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Facile and Convenient Method for Deprotection of Thiocarbonyls to Their Carbonyl Compounds Using Oxone Under Aprotic and Nonaqueous Conditions

The reaction of oxone as an inexpensive, stable, and commercially available reagent with thiocarbonyl compounds in refluxing acetonitrile has been studied. Primary, secondary, and tertiary thioamides and thioureas are converted to their oxo analogues efficiently. Thiono esters also are transformed to their corresponding esters, while thioketones remained intact under these conditions.

Bismuth(III) nitrate pentahydrate: a convenient and selective reagent for conversion of thiocarbonyls to their carbonyl compounds

A variety of thioamides and thioureas are rapidly transformed to their oxo derivatives with Bi(NO 3) 3·5H 2O in excellent yields. However, thiono esters and thioketones are converted to their corresponding carbonyl compounds in only poor yields. Bi(NO 3) 3·5H 2O is relatively non-toxic, insensitive to air and inexpensive. These features coupled with the selective deprotection of thioamides and thioureas in the presence of thiono esters and thioketones make this method an attractive alternative to the existing routes for deprotection of thiocarbonyl compounds.

Quantitation of tolnaftate by spectrophotometric methods in pharmaceutical formulations

Two selective spectrophotometric methods are described for the assay of tolnaftate in single and​/or combined pharmaceutical formulations. The first one depends on the formation of a methylene blue dye (λmax 665 nm) by the reaction of N,​N-​di-​Me p-​phenylene diamine dihydrochloride in the presence of ceric ammonium sulfate with sodium sulfide resulting from the alk. hydrolysis of the thiono ester-​tolnaftate. All variables affecting hydrolysis of tolnaftate were studied. Also other parameters affecting the color development as sulfuric acid and reagent concns., reaction time, temp. and diln. solvents were optimized. The second method depends on the simultaneous estn. of tolnaftate and clioquinol in the presence of gentamycin sulfate and betamethasone by the measurement of the first deriv. spectrum in

Synthesis, characterization and decomposition patterns for thienylene bridged dinuclear biscarbene complexes of manganese and chromium in refluxing carbon disulphide and acetone

The dinuclear complexes [ML 3(CO) 2{C(OEt)C 4H 2SC(OEt)}M(CO) 2L 3] (M=Cr, L=CO 1; M=Mn, L 3= η 5-C 5H 4R, R=H 2 and Me 3) were synthesized from dilithiated thiophene according to the Fischer-method. The highly reactive biscarbene complexes are unstable in acetone and react to afford [ML 3(CO) 2{C(OEt)C 4H 2SC(O)OEt] (M=Cr 4, M=Mn, R=H 5 and Me 6). When refluxed in carbon disulphide, 1 affords as the only isolable product 4, whereas 2 and 3, in addition to 5 and 6, reacts with CS 2 to give the thiono ester compounds [Mn( η 5-C 5H 4R)(CO) 2{C(OEt)C 4H 2SC(S)OEt}] with R=H 7 and Me 8, respectively. Compound 1 crystallizes in the monoclinic space group C2/c with a=21.593(12), b=10.235(3), c=22.531(12) Å, β=92.06(4)° and Z=8.

ELECTROREDUCTION OF ORGANIC COMPOUNDS, 29∗

Abstract O-Methyl thiopivalate 3 yields bis(1-methoxy-2,2-dimethylpropyl)disulfane 6 and 3,5-di-tert-butyl-1,2,4-trithiolane 8 on electroreduction in methanol. Thiono ester 3 formed by transesterification is also the source of 6 which is found as product on electroreduction of 4-chlorobutyl (1) and 5-chloropentyl dithiopivalate 2.—The deutero derivatives 12 and 13 result from the electroreduction of 3 in methan[D]ol.

Peptide Thioacylation with High Stereochemical Preservation

A dipeptide thioamide model system, Boc-Leu-ψ[CSNH]-MetOMe, was used for evaluating the preservation of amino acid stereochemistry during thioacylation utilizing amino monothio acids. The LL and DL peptide diastereomers were separated by use of high performance capillary electrophoresis (micellar electrokinetic capillary chromatography). The described thioacylation method combines monothio acids with coupling reagents of the PyBOP-family for generating active thiono esters with low-levels of enantiomerisation (<2%). The best results in terms of stereochemical preservation and yield were obtained with PyNOP, a 6-nitro analog of PyBOP. The successful activation of thiobenzoic acid with all four coupling reagents extended the scope of the method to include aryl monothio acids.

Thiono, Selenothiono, and Dithiocarboxylic Ester Complexes from Pentacarbonyl(thiobenzaldehyde)tungsten and π‐Donor Substituted Alkynes and Decomplexation of the Esters

AbstractPentacarbonyltungsten‐coordinated thiobenzaldehyde, [(CO)5W{S=C(Ph)H}] (1), reacts with 1‐methylthio‐1‐propyne, 1‐ethylseleno‐1‐propyne, and alkoxyethynes by insertion of the CC into the S=C bond to form in a highly regio‐and stereoselective manner the α,β‐unsaturated dithio, selenothiono, and thionocarboxylic ester complexes (E)(CC)‐[(CO)5W{η1‐SC(XR′)C(R)=C(Ph)H}] (3) (R = Me: XR′ = SMe (a), SeEt (b); R = H: XR′ = OEt (c), OtBu (d)). The analogous reaction of 1 with bis(alkylthio)ethynes affords mixtures of the (E) and (Z)(C=C) isomers of [(CO)5W{η1‐S=C(SR)C(SR)=C(Ph)H}] (6) [R = Me (a), tBu (b)]. The Z isomers are the initially formed products. Formation of (Z)‐6 is followed by Z → E isomerization until an equilibrium [E/Z = 1 (6a), 1.5 (6b)] is obtained. For R = tBu isomerization is significantly faster than for R = Me. The dithio and thiono ester ligands can be cleaved intact from the metal by treatment with [NEt4]Br as shown by the examples of 3a, 3c, and 6a. Complex 3c has been characterized by an X‐ray structural analysis.

Synthesis of α-OxoketeneO-Alkyl/Aryl,S-Alkyl Acetals

The synthesis of acylketene 0,5-dialkyl acetals 2 a-p and acylketene O-aryl S-alkyl acetals 6 a-i is described. The compounds 2a-n are obtained by base-catalyzed alkylation of the respective β-oxo thiono esters 4 a-n prepared by alkoxythiocarbonylation of active methylene ketones in the presence of sodium tert-butoxide. The corresponding O-dodecanyl 2o, O-benzyl 2p and O-aryl, S-methyl 6a-i acetals are synthesized via base-catalyzed displacement of the sulfonium salts 5a-b with the corresponding alkanol or phenol

Dithio‐ und Thionester, 55. Synthese von N‐geschützten, optisch aktiven α‐Aminothionsäureestern

Dithio and Thiono Esters, 55. — Synthesis of N‐Protected, Optically Active α‐Amino Thiono EstersThe N‐protected α‐amino amides 1 are O‐alkylated with trialkyloxonium tetrafluoroborates to form the iminium salts 2. Sulfhydrolysis of 2 yields the α‐amino thiono esters 3. This reaction sequence allows the preparation of enantiomerically pure 3.

Dithio‐ und Thionester, 56. Zur Reaktion von Thioestern und Thioamiden mit Azodicarbonsäurederivaten

Dithio and Thiono Esters, 56. — Reaction of Thio Esters and Thio Amides with Azodicarboxylic Acid DerivativesDithio and thiono esters 1 react with azodicarboxylates 3 to form the addition products 4 or the oxidation products 5 in varying ratios. With malonates, malonamides and dithionomalonates only the addition products 7 were obtained. N,N,N′,N′‐Tetramethyldithiomalonamide yields with azodicarboxylic acid derivatives 3 either the normal addition product 8, the β‐elimination product 9 or N,N,N′,N′‐tetramethyltrithiomesoxalamide (10A), the first stable vicinal trithiocarbonyl compound.

Dithio- und Thionester, 53. DarstellungN-geschützter α-Aminodithiosäureester aus α-Aminonitrilen und α-Aminocarbonsäuren

Dithio and Thiono Esters, 53. — Synthesis of N-Protected α-Amino Dithioesters from α-Amino Nitriles and α-Amino Acids The α-amino nitriles 1 and 5 have been transformed into the thiolimido ester hydrochlorides 2 and 6 and sulfhydrolyzed to give the N-protected α-amino dithioesters 3 and 7. The α-amino dithioesters 10 were obtained from 1 via the thioamides 8 and their S-alkylation products 9. The optically active thioamides 12, prepared from naturally occurring L-α-amino acids, were converted into the optically active α-amino dithioesters 7. The optical purity of the N-protected dithioalanine esters 14 was determined by an HPLC analysis of the diastereomeric menthyloxycarbonyl derivatives 17.

The preparation and reactions of protected glyphosate imidate, thioimidate, and thiono esters from N-[diphenoxyphosphinylmethyl]glycinonitrile: Comparative reactivities of activated carboxylate versus phosphonate esters

The highly efficient syntheses of novel protected glyphosate imidate, thioimidate, and thiono ester derivatives are described starting from N-[diphenoxyphosphinylmethyl]glycinonitrile 3b. The scope, utility and limitations in using each of these activated carboxylate functionalities for further transformations to new “masked” heterocyclic derivatives are defined. While the solution stability of the imidate and thioimidate series limited the synthetic application of these species, the corresponding thiono ester derivatives were valuable synthetic intermediates, providing a short, efficient route to the first glyphosate derivatives containing 1,3,4-oxadiazole and 1,2,4-triazole ring systems in place of the carboxylate group. These thiono esters thus undergo selective nucleophilic addition at this activated carboxylate center, while retaining the reactive diphenyl phosphonate moiety.