Thiopyrones

I-Pyran-4-thiones (4-thiopyrones) may be obtained from 4-pyrones with phosphorus pentasulfide (e.g., cf. King et (the... 

Thiopyrones and selenopyrones can be alkylated more readily than pyrones. Thus 2,6-dimethyl-4/f-pyran-4-thionc (4,6-dimethyl-4-thiopyrone) (23, Y = S) reacts rapidly with methyl iodide yielding a 4-methylmercaptopyrylium iodide (24, Y = S, R = Me, X = I). Many alkylating agents were investigated by King et al. The kinetics of the reaction between 2,6-dimethyl-4-thiopyrone and substituted phenacyl bromides was found to be described by the Hammett... 

The usual carbonyl reagents (hydrazines, semicarbazone, hydroxyl-amine) do not give the normal derivatives, but lead to ring contraction and formation of pyrazoles or isoxazoles. However, a semicarbazone and an oxime of 2,6-diphenylpyrone has been obtained by Arndt et al., indirectly, through the intermediacy of the more reactive 4-thiopyrone. 

E. Thiopyrans from Thiopyrones and Similar Cyclic Ketones.. . . ... 

A high regioselectivity was observed for both silylation and phosphorylation of various 2,3-dihydro-4//-thiopyrones, affording 2//-thiopyrans 108a-f in almost quantitative yields (83YZ1096 90TL845 91CJC1487). 

The cyclic sulfone 4-thiopyrone-5, 5-dioxide also exhibits enhanced reactivity as a result of the effect of the sulfone dipole.103... 

Influenced by P. Pfeiffer s 1922 paper, postulating separated charges (Zwitterions) within aminoacids, Arndt wrote formulas for gamma pyrone and gamma-thiopyrone as "Zwitterion" dipolar molecules ... 

The sulfonyl group in sulfones resists catalytic hydrogenation. Double bonds in a, -unsaturated sulfones are reduced by hydrogenation over palladium on charcoal (yield 94%) [686, 687] or over Raney nickel (yield 62%) without the sulfonyl group being affected [686]. In p-thiopyrone-1,1-dioxide both double bonds were reduced with zinc in acetic acid but the keto group and the sulfonyl group survived [655]. Raney nickel may desulfurize sulfones to hydrocarbons [673]. 

Pyrones and thiopyrones react very readily with a variety of nucleophiles, but here the situation is complicated not only by the carbonyl group, but by the fact that these compounds show elements of both aromatic and aliphatic character. Pyran-2-one (9) can in principle react with nucleophiles at the 2-, 4- or 6-position and examples of each type of reaction are known. There is an approximate correlation with the hard and soft acid and base hypothesis, in that hard nucleophiles such as HO generally react at the 2-position while soft nucleophiles such as hydride ion generally react at the 6-position. Reactions at the 4-and 6-positions can, of course, be rationalized mechanistically simply as examples of conjugate addition. A similar situation obtains with pyran-4-ones (10), where reaction can in principle occur at the 2- or 4-position. Hard nucleophiles generally react at the 2-position,... 

Only rare reports of the conversion of thiopyrones to thiopyrans are available. Unsubstituted 4-thiopyrone (335) was reduced with aluminum hydride to the corresponding 4-thiopyranol (2).5,90 A precipitate formed during the reaction of thiopyrone 336a with thionyl chloride was regarded to be a 4H-thiopyran derivative (336b).325... 

The ferricyanide oxidation of 4//-thiopyrans 206b to corresponding dioxocyclohexylidene derivatives 423 proceeds in the same manner as in the pyran series.250 Simple 4-thiopyrone (325) and mesoxalic acid were isolated after oxidation of 4-hydroxy-4//-thiopyran (2) with potassium permanganate.4... 

Quinolin-4-one forms a 3-bromo derivative, but coumarin gives the addition compound (116) which is easily re-aromatized (116 — 117). 4-Thiopyrones are halogenated in position 3. Pyridazinones and cinnolinones are also readily halogenated in the expected position. 

Photolysis of phenyl 2-thenoate leads to a 3 2 mixture of ortho and para Fries rearrangement products (Scheme 109) (74H(2)423). The photolytic rearrangement of a thiolester to a thiopyrone has been investigated with thiophenecarbothioic acid S-aryl esters as substrates (79LA2043). In the case of the 2-carbothioic acid esters, a 3-bromo substituent is necessary for this rearrangement. On the other hand, such a substituent is not necessary for the 3-carbothioic acid derivatives. In both cases, aldehydes may also be formed, sometimes as the main products (Scheme 110). 

Whereas zwitterionic forms may be invoked to explain the properties of 2- and 4-thiopyrones, the 3-thiopyrone can only exist as the betaine (42) and is therefore to be compared with the pyridinium system for a bonding and structural likeness. A theoretical treatment (73JPR690) has been published using CNDO/2 methods, and the calculated parameters were found to agree well with experimentally determined spectral properties. 

Electron density calculations for HOMOs and LUMOs of the 2- and 4-thiopyrones (73JPR690) have been used to rationalize the sites of reactivity within the molecules (67AHC(8)219). Scheme 1 illustrates the general conclusions. 

Electrophiles such as halogen attack 4-thiopyrones in position 3 while alkylation occurs on the exocyclic oxygen or sulfur atom to form a thiopyrylium cation. Nitration with nitric acid is unsuccessful because the acid protonates the ketone and the thiopyrylium produced is no longer nucleophilic (Scheme 18). 

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