Thioethers from aromatic compounds

Electronically excited carbonyl chromophores in ketones, aldehydes, amides, imides, or electron-deficient aromatic compounds may act as electron acceptors (A) versus alkenes, amines, carboxylates, carboxamides, and thioethers (D, donors). In addition, PET processes can also occur from aromatic rings with electron-donating groups to chloroacetamides. These reactions can be versatile procedures for the synthesis of nitrogen-containing heterocyclic compounds with six-membered (or larger) rings [2],... 

An impressive number of papers and books has been published and numerous patents have been registered on the aq lation of aromatic compounds over solid catalysts. Recently Sartori and Maggi [1] have written an excellent review with 267 references on the use of solid catalysts in Friedel-Crafts acylation. In one section of this review, namely acylation of aromatic ethers or thioethers, the authors report work on acylation by solid catalysts such as zeolites, clays, metal oxides, acid-treated metal oxides, heteropolyacids or Nafion. When examining in details these results, it appeared very difficult for us to build upon these experimental results as the reaction conditions differ drastically from one paper to the next. This prompted us to reinvestigate the scope and limitations of the Friedel-Crafts acylation using heterogeneous solids as catalysts, trying as much as we could to rationalize the observed effects. 

An alternate and more controlled approach to the synthesis of phenothiazines involves sequential aromatic nucleophilic displacement reactions. This alternate scheme avoids the formation of the isomeric products that are sometimes observed to form from the sulfuration reaction when using substituted aryl rings. The first step in this sequence consists of the displacement of the activated chlorine in nitrobenzene (30-1) by the salt from orf/io-bromothiophenol (30-2) to give the thioether (30-3). The nitro group is then reduced to form aniline (30-4). Heating that compound in a solvent such as DMF leads to the internal displacement of bromine by amino nitrogen and the formation of the chlorophenothiazine (30-4). Alkylation of the anion from that intermediate with 3-chloro-l-dimethylaminopropane affords chlorpromazine (30-5) [31]. 

Hauptmann et al. found that aromatic disulfides, thioesters, and thiols were transformed into thioethers when refluxed in xylene (140°C) in the presence of Raney Ni degassed at 200°C.130,134,135 However, when these compounds were heated at 220°C with degassed Raney Ni or reduced Ni, biphenyls were obtained in good yields. The yields of the products with Raney Ni degassed at 500°C were never lower and were sometimes higher than those obtained with Raney Ni degassed at 200°C, as seen from an example shown in eq. 13.64. On the basis of these results, it was concluded that the presence of hydrogen was not essential for these desulfurizations.136... 

Notable new general syntheses of butenolides include the addition of the three-carbon synthon Li(PhS)C=CMeC02Me to aldehydes R CHO (R = alkyl or aryl) to yield the thioethers (19), the related reaction of lithio-j8-lithio-acrylates R CLi=CR C02Li with benzaldehyde to give compounds (20 R = H or Me), and the formation of (21) from the iodinated allyl alcohol ICMe=CHCH20H and carbon monoxide in the presence of bis(triphenylphos-phine)palladium(ii) chloride. Chloral reacts with dimethyl (benzylamino)fu-marate to yield the butenolide (22), whereas aromatic aldehydes give hydroxy-pyrrolinones (23). The total synthesis of piperolide (24) has been reported. 

Imidazoles.—Formation. Several new syntheses of imidazoles from isocyanides have been reported these include the formation of 1-alkyl-imidazoles (396) by the action of primary amines on 2-isocyano-2-tosylstyrene, PhCH=C-(NOTos, the cyclization of the enamine Me2NCH=C(NC)C02Me to compound (397) in the presence of methyl iodide,and the preparation of the ethers or thioethers (398) from isocyano-cyanides R CH(NC)CN by their reaction with alcohols or thiols R XH, respectively.Aromatic aldehydes are converted into 2-aryl-4,5-dichloroimidazoles (399) by the combined action of cyanogen and hydrochloric acid. 5-Acetyl-4-methylimidazole (400) results when form-amido-acetylacetone, AC2CHNHCHO, is heated with formamide and formic acid. Exhaustive chlorination of tetramethyldithio-oxamide leads to the tri-chloro-imidazolium cation (401). ... 

Sulfur-containing compounds (thiols and sulfides) are easily recognized from the M -h 2 isotopic peak each sulfur contributes 4.4% to the abundance of the M -I- 2 ion. The fragmentation patterns of thiols (mercaptans) and sulfides (thioethers) parallel the corresponding alcohols and ethers. For example, similar to the alcohol series at m/z 31,45, 59,..., the a-cleavage in thiols produces a series of ions at m/z 47, 61, 75, 89,..., and each ion has a satellite peak 2 u higher, due to In addition, thiols exhibit a characteristic loss of H2S, followed by the elimination of alkene moieties to produce peaks at (M — 34)+, (M — 34 — 2114)+, and so on. In contrast, secondary thiols show a characteristic peak at (M — SH)+. Aromatic thiols also behave similarly to phenols under El conditions. In addition, they show ions at (M — S)+, (M — SH)+, and (M — 2114)+. ... 

Sulfoxidation. Heteroatom oxidation catalyzed by (halo)peroxidases has been observed in a variety of organic compounds. Ai-Oxidation in amines, for instance, can lead to the formation of the corresponding aliphatic A-oxides or aromatic nitroso or nitro compounds. From a preparative standpoint, however, sulfoxidation of thioethers is of greater importance since it was shown to proceed in a highly stereo- and enantioselective fashion. Moreover, depending on the source of the haloperoxidase, chiral sulfoxides of opposite configuration could be obtained (Scheme 2.179). 

Alkylation is used in the derivatization of additives and analytes containing active hydrogen atoms, aliphatic or aliphatic-aromatic substituents. This method is also used to modify compounds containing acidic hydrogen, such as carboxylic acids and phenols, which are converted into esters. Alkylation reactions can also be used to prepare ethers, thioethers and thioesters, N-alkylamines, amides, and sulfonamides. Although silyl derivatives of carboxylic acids are easily formed, these compounds suffer from low stability. 

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