From 1,2-Dithiolans

From 1,2-Dithiolans (Type C).—Several variations of the general synthesis of isothiazoles from 1,2-dithiolans (see these Reports, Vol. 2, p. 563) have been employed in the production of further series of isothiazole deriv-atives. In a comparative study, this route has been described as the most generally applicable method of preparing di- and tri-alkylisothiazoles.  

The action of Grignard reagents on N-(5-aryl-3H-l,2-dithiol-3-ylidene)-arylamines (10) provides the 1,3-bifunctional reagents (11), which have proved to be versatile starting materials in heterocyclic syntheses. Their oxidation with iodine produces isothiazolium iodides (12) in 29—34% yield. 

The work, incidentally, disproves a previous assignment of the structure (12 Ar = R = Ph) to the product of the successive sulphurization and quatemization of 2,5-diphenylisothiazolium perchlorate (13) this compound is non-identical with authentic material now obtained, and is in fact the dithiolan derivative (14).  

2-Dithiolans Type C). The general synthesis of isothiazoles from 1,2-dithiolans (see Vol. 2, p. 563 Vol. 3, p. 543) by reaction with ammonia or amines continues to be exploited. 3-Ethoxy-l,2-dithiolium salts (1) are cleaved by primary amines to the linear thioesters (2), which are in turn convertible into 

From -Aminocrotonic Esters Type C). The synthesis of isothiazoles from j3-aminocrotonic esters (see Vol. 1, p. 370) has been exemplified by the condensation of p-nitrobenzoyl and 2-furoyl isothiocyanates (6) with ethyl j8-methylamino-crotonate (7), which produces pyrimidine derivatives (5) in the absence, and substituted isothiazoles (8) in the presence, of oxidizing agents such as bromine. 

Under standard conditions 5-nitrofuroyl isothiocyanate reacts with the enamine to give the isothiazoles (8) directly.  

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Data on the separation of thietane by gas chromatography have been reported along with data on other sulfur compounds. Thin-layer chromatographic separation of thietane from 1,2-dithiolane and 1,2.3-trithiane works well on silica gel. Thietane forms a hydrate (dec 11.7°) with water. Its clathrate structure was investigated by use of the nmr line shapes of the deuterium oxide hydrate. ... 

The preparation of e/n-difluoro compounds by the oxidative fluorodesul-furization ot 1,3-dithiolanes readily proceeds by treatment with a pyridinium polyhydrogen fluoride-Af-halo compound reagent the latter serves as a bromonium ion source [2], l,3-Dibromo-5,5-dimethylhydantoin is the most effective of several At-halo oxidants. It is believed that /V-halo compounds combine with hydrogen fluoride to generate in situ halogen fluorides, the oxidants. Formation of gem-difluorides from dithiolanes derived from ketones is efficient and rapid, even at -78 °C, whereas the reaction of dithiolanes derived from aldehydes requires higher temperature (0 °C) (equation 4). 

Trifluoromethyl thioketones, also generated from dithiolane oxides by flash vacuum pyrolysis, can be condensed at low temperature with dienes to give the cycloadducts (Table 5)." ... 

The formation of the carbonyl product was accompanied by the formation of either 1,2-ethanedithiol or 1,3-propanedithiol (from dithiolanes or dithianes, respectively). 

An original method has recently been developed starting either from 1.3-dithiolane (10) or from 1.3.4-thiadiazole-2-thione derivatives (11) (Scheme 4) (3). This method does not work when Ri is an aryl group. 

Aromatics containing electron releasing groups such as phenols, dim ethyl am in oben 2en e and indole are formylated by 2-ethoxy-l,3-dithiolane in the presence of boron trifluoroetherate, followed by hydrolysis (114). The preformed dithiolanium tetrafluoroborate also undergoes Friedel-Crafts reaction with aromatics such as dim ethyl am in oben 2en e and indole (115), and was used to generate dithiolanium derivatives (formyl precursors) from the enoltrimethylsilyl ether derivatives (116). 

Acyclic monothio acetals and ketals can be prepared directly from a carbonyl compound or by transketalization, a reaction that does not involve a free carbonyl group, from a 1,3-dithiane or 1,3-dithiolane. They are cleaved by acidic hydrolysis or Hg(II) salts. 

Oxidation of a thiiraneradialene with equimolar amounts of MCPBA in CH2C12 at about 0°C gave the corresponding thiiraneradialene S-oxide 26 in a quantitative yield47 (equation 11). 5-Membered heterocyclic sulphoxides such as 1,3-benzoxathiolane sulphoxide 27, 1,3-benzdithiolane sulphoxide 28 and 1,3-dithiolane sulphoxide 29 were readily obtained from their sulphide precursors by oxidation with MCPBA in dich-loromethane solution48. 

The modified Sharpless reagent was also successfully applied288 for the asymmetric oxidation of a series of 1,3-dithiolanes 248 to their S-monooxides 249 (equation 134). It was observed that the optical induction on sulphur (e.e. from 68 to 83%) is not significantly affected by the substituents R1 and R2. Asymmetric oxidation of a few aryl methyl sulphides by organic hydroperoxides in the presence of a catalytic amount of the optically active Schiff base-oxovanadium(IV) complexes gave the corresponding sulphoxides with e.e. lower than 40%289. 

Pyridyl-l,3-dithianes (50) result from the reaction of picolyl lithium reagents with 1,2-dithiolanes in the presence of HMPT. An initial ring opening is followed by reaction at the carbanion site with a second mole of dithiolane <96PS(112)101>. 

In the synthesis of l,3-dithiolan-2-ones from spirocyclic intermediates, via episulfides, substituted tetrathiacyclododecane and the related pentathiacyclopentadecane were isolated in good yields <96JCS(P1)289>. Preparation and molecular dynamics studies of 2,5,8,17,20,23-hexathia[9.9]-p-cyclophane have been reported <96P4203>. The syntheses and properties of thiocrowned l,3-dithiole-2-thiones and their conversion to tetrathiafiilvenes via treatment with triethylphosphine have been described <96LA551>. 

The regeneration of carbonyl compounds from dithioacetals and dithiolanes is often done with reagents that oxidize or otherwise activate the sulfur as a leaving... 

Lactones can be protected as dithiolane derivatives using a method that is analogous to ketone protection. The required reagent is readily prepared from trimethyl-aluminum and ethanedithiol. 

A more complex structure is that of leinamycin 45 (Scheme 15), a material with potent cytotoxic and antitumor properties, isolated from a Streptomyces sp. A 1,2 dithiolane-3-one ring is spiro fused to a complex macrolactam96 (and references therein). Leinamycin has the remarkable ability to cleave DNA. In brief, leinamycin reacts with a thiol and, after a profound rearrangement, forms an episulfonium ion. This ion alkylates the N7 position of guanosine residues in double stranded DNA an unstable adduct is depurinated by hydrolysis of the glycosidic bond between the alkylated base and a deoxyribose residue. Some structurally less complex l,2-dithiolane-3-one 1-oxides have a similar DNA cleaving ability.97... 

The procedure for the preparation of a dithiolane from a hydroxy-methylene derivative of a ketone and ethylene dithiotosylate (ethane-1,2-dithiol di-p-toluenesulfonate) can be varied to produce dithianes when the latter reagent is replaced by trimethylene dithiotosylate.8,4 The dithiotosylates also react with enamine derivatives to produce dithiaspiro compounds.4,5... 

The preparation of dithianes from enamines by reaction with trimethylene dithiotosylate (propane-1,3-dithiol di-p-toluenesulfonate) has been applied with enamines derived from oholostan 3 one, aceto-acetic ester, and phenylacetone.6 7 Reactions of trimethylene dithiotosylate with hydroxymethylene derivatives of ketones also give rise to dithianes thus the hydroxymethylene derivative of cholest-4-en-3-one can be converted to 2,2-(trimethylenedithio)cholest-4-en-3-one. 1,3-Dithiolanes are obtained in a similar manner by reaction of ethylene dithiotosylate1 with the appropriately activated substrate.5,7... 

Secondary alkyl selenides are reduced by (TMS)3SiH, as expected in view of the affinity of silyl radicals for selenium-containing substrates (Table 4.3) [40]. Reaction (4.23) shows the phenylseleno group removal from the 2 position of nucleoside [50]. Similarly to 1,3-dithiolanes and 1,3-dithianes, five- and six-membered cyclic selenoacetals can be monoreduced to the corresponding selenides in the presence of (TMS)3SiH [51]. The silicon hydride preferentially approached from the less hindered equatorial position to give transicis ratios of 30/70 and 25/75 for the five-membered (Reaction 4.24) and six-membered cyclic selenoacetals, respectively. 

A predator odor affected a pocket gopher, Thomomys talpoides, population in western Canada. First live-trapping removed the gophers from plots of 4ha area in an orchard. Then synthetic sulfur compounds from stoat, Mustek erminea anal glands (1 1 mixture of 2-propylthietane and 3-propyl-l,2-dithiolane) were... 

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