Cyclic Thiohydroxamic Acids Research Articles

A study on the stereoselectivity of C,O bond formation in esterification of cyclic thiohydroxamic acids

Esterification of cyclic thiohydroxamic acids, for example, N-hydroxypyridine-2(1 H)-thione, N-hydroxy-4-methylthiazole-2(3 H)-thione, and N-hydroxy-4-( p-chlorophenyl)-thiazole-2(3 H)-thione, occurred with inversion of configuration at the attacked stereocenter, as evident from the use of chiral alcohols, alkyl p-toluene sulfonates, and cyclic sulfates. Stereochemical analysis of enantiomerically pure O-alkyl thiohydroxamates was performed on the basis of CD-spectroscopy and chemical derivatization. The assignment of the relative configuration in cyclic O-esters was feasible via NMR spectroscopy, whereas chiral aliphatic glycolato monoesters required hydroxyl group derivatization with chloro-(4 R,5 R)-bis[(1 R,2 S,5 R)-menth-1-yloxycarbonyl)]-1,3,2-dioxaphospholane for this purpose.

Hindered rotation in N-acyloxy-4-methylthiazole-2(3 H)-thiones

Experimentally determined barriers to O-acyl group topomerization in mixed anhydrides composed of β-disubstituted carboxylic acids and cyclic thiohydroxamic acid N-hydroxy-4-methylthiazole-2(3 H)-thione were located in the range of Δ G ‡ 320=68±8 kJ mol −1 (DNMR). According to modeling studies, the underlying exchange process is proposed to occur via rotation about the N,O bond for torsional movement of the O-acyl group past the heterocyclic 4-methyl substituent. The energetically lowest pathway for passing the O-acyl entity by the thione sulfur, is predicted to occur via sequential rocking about the C sp 2 ,O single bond in combination with an interlaced twist about the N,O axis.

Solid-state study of cyclic thiohydroxamic acids: 1-hydroxy-2(1H)-pyridinethione and 3-hydroxy-4-methyl-2(3H)- thiazolethione

Cyclic thiohydroxamic acids such as 1-hydroxy-2(1H)-pyridinethione (1) and 3-hydroxy-4-methyl-2(3H)-thiazolethione (2) find diverse applications as fungicides and alkoxy-radical precursors. Selected physico-chemical properties such as thermal stability can be rationalized by examination of their solid-state structures. We report here a new hydrated form of 2 (denoted 3) that displays enhanced thermal stability and solubility compared with the anhydrous form. These enhanced properties may be attributed to the ionic nature of 3 in the solid state. The oxidized form of 1, 2,2′-dithiobis(pyridine-1-oxide) (DTPO, 4) also finds application as a fungicide. Attempts to produce an analogous disulfide from 2 produced a new thioether product, 3-hydroxy-4-{[3-oxo-4-methyl-2(3H)-thiazol-2-yl]thio}-2(3H)-thiazolethione (5). Co-crystallization of 1 with 2 produced a mixed molecular crystal (6) containing both DTPO and a new thioether derivative of 2, 5,5′-thiobis[3-hydroxy-4-methyl-2(3H)-thiazolethione]. The supramolecular complementarity of the two components gives rise to discrete hydrogen-bonded dimers within the co-crystal. Copyright © 2000 John Wiley & Sons, Ltd. Additional material for this paper is available from the epoc website at http://www.wiley.com/epoc

The Use of Propane Phosphonic Acid Anhydride (PPAA) in the Synthesis ofN-Acyloxythiazole-2(3H)-thiones

A mild and efficient new method for the preparation of O-acyl derivatives of N-hydroxythiazole-2(3H)-thiones and N-hydroxypyridine-2(1H)-thiones (Barton-anhydrides) for cyclic thiohydroxamic acids, carboxylic acids, propane phosphonic acid anhydride (PPAA) and 1,4-diazabicyclo[2.2.2]octane (DABCO) was developed.

On the SelectiveO-Alkylation of Ambident Nucleophiles – The Synthesis of Thiohydroxamic AcidO-Esters by Phase-Transfer Reactions

O-Alkylation of cyclic thiohydroxamic acids 1 and 3–5 has been studied with a view to developing an efficient method for the synthesis of N-(alkoxy)pyridine-2(1H)-thiones and N-(alkoxy)thiazole-2(3H)-thiones. Four issues have been addressed and the following conclusions can be drawn: (i) Thiones 1 and 5 exist as O–H acids in the solid state. (ii) According to NMR investigations (1H, 13C), the thione structures should be largely retained in CDCl3, [D6]DMSO, and CD3OD solutions of acids 1, 3–5, as is also the case for pyridinethione salts 2a–h. (iii) O-Alkylation of pyridinethione salts occurs in competition with S-alkylation. Selective O-alkylation is however possible, if thiohydroxamate salts with large countercations, such as M = NBu4, are treated with hard alkylating reagents in polar aprotic media. (iv) As tetrabutylammonium thiohydroxamates, such as 2f, are highly useful in the synthesis of cyclic thiohydroxamic acid O-esters, we have developed an efficient protocol for the preparation of N-(alkoxy)pyridine-2(1H)-thiones directly from acid 1 using phase-transfer conditions (alkyl halide or sulfonic acid ester, CH3CN, K2CO3, Bu4NHSO4). This method has proved particularly successful for the synthesis of N-(alkoxy)thiazole-2(3H)-thiones 11, 20–28, which were obtained in yields of up to 87%.

Hydrogen Bonding in 1-Hydroxy-4(1H)-pyridinethione

The crystal lattice of the title compound, C5H5NOS, a vinylogous cyclic thiohydroxamic acid, comprises a network of hydrogen bonds [O—H = 1.16 (3) A, O⋯S = 2.971 (2) A, H⋯S = 1.82 (3) A, O-H⋯S = 171 (1)°], with the hydroxyl moiety as hydrogen-bond donor and the S atom as acceptor. According to the observed C—S distance of 1.718 (2) A, the sulfur–carbon bond in the title compound is closer to a single than a double bond. The sum of bond angles at N1 is 360.8° which suggests a planar arrangement of the N—O group with respect to the carbon framework of the heterocycle.

ChemInform Abstract: Nitrones and Oxaziridines. Part 36. Synthesis of Cyclic Thiohydroxamic Acids.

AbstractA reliable and high‐yielding method is presented to transform cyclic hydroxamic acids (IV) to cyclic thiohydroxamic acids (IX)/(X) via the respective methyl ethers (VI) and (VIII).

Nitrones and Oxaziridines. XXXVI. Synthesis of Cyclic Thiohydroxamic Acids

2-Cyano-1-pyrroline 1-oxides (1) could not be converted directly into the related cyclic thiohydroxamic acids (8). Potassium ethyl xanthate transformed nitrones (1) into the imidates (2). The cyclic hydroxamic acids (4) can be converted into the thiohydroxamic acids (8) via the methoxypyrrolidinones (5) and the methoxypyrrolidine thiones (6), making use of sodium p- tolylmercaptide as the demethylating agent. Reaction of methoxy thiones (6) with trimethylsilyl iodide led to the formation of the 2-methylthio-1-pyrroline 1-oxides (7).

Growth Repression of Higher Plants by 2-Pyridinethiol, 1-Oxide.

The compound 2-pyridinethiol, 1-oxide and its salts have been reported to have pronounced antibacterial and antifungal activity of a type that, were it a microbiological product, would cause it to be classed as a broad-spectrum antibiotic (5, 8). This property is shared by a number of other cyclic thiohydroxamic acids, variously substituted, though some are much more active than others. The high potency of this grouping, and. the diversity of microorganisms to which compounds containing it are inhibitory, suggest interference with some essential metabolic process. Furthermore, certain antibiotics of comparable potency have been found to repress growth in some plant systems (1, 3, 4). Accordingly, the activity of 2-pyri-

The Influence of Certain Sugars on the Antifungal Activity of Sodium Pyridinethione

Shaw et al. (8) synthesized a cyclic thiohydroxamic acid from 2bromopyridine N-oxide and reported a high in vitro activity against a variety of organisms. Pansy et al. (7) found this compound, 1-hydroxy2(1H) pyridinethione, to be extremely effective in controlling fungi in vitro at concentrations of 0.04-1.0 ppm. Soo-Hoo and Grunberg (9) conducted studies with various salts of 3-pyridinethiol with good re? sults against dermatophytic as well as phytopathogenic fungi. Modifications of medium constituents apparently are effective in altering the activity of some antibacterial compounds. Di Raimondo (4) reported that the vitamin B complex reduced the activity of the anti? biotics terramycin and tyrothricin against Micrococcus pyogenes var. aureus. According to Weinberg (10), the inhibition of Mycobacterium avium by the antibiotics aureomycin and terramycin is significantly increased by the addition of phosphate to the medium. In this investigation, four different carbohydrate sources were em? ployed separately in conjunction with varying concentrations of sodium pyridinethione (the sodium salt of 2-pyridinethiol, 1-oxide 2) to deter-

Analogs of Aspergillic Acid. IV. Substituted 2-Bromopyridine-N-oxides and Their Conversion to Cyclic Thiohydroxamic Acids1

Analogs of Aspergillic Acid. IV. Substituted 2-Bromopyridine-N-oxides and Their Conversion to Cyclic Thiohydroxamic Acids¹