Sulfur nucleophiles aromatic nucleophilic substitution

With Sulfur Nucleophiles N-Carboxy-protected aziridine-2-carboxylates react with thiols to give P-mercapto-ot-amino acid derivatives. The reaction is usually catalyzed by BF3 and the yields range from fair to excellent [15, 16, 108-111]. With N-unprotected 3-substituted aziridine-2-carboxylates, the ring-opening with thiols usually takes place with anti stereoselectivity, especially in the case of the C-3 aliphatic substituted substrates. In cases in which C-3 is aromatic, however, the stereoselectivity has been found to be a function of the substitution pattern on the aromatic ring 3-p-methoxy ph eri yl-su bs li In led aziridines 143a (Scheme 3.51) and... 

All the mechanisms so far discussed take place at a saturated carbon atom. Nucleophilic substitution is also important at trigonal carbons, especially when the carbon is double bonded to an oxygen, a sulfur, or a nitrogen. Nucleophilic substitution at vinylic carbons is considered in the next section at aromatic carbons in Chapter 13. 

Since these methoxylated and acetoxylated sulfides have an acetal structure, it is expected that Lewis acid catalyzed demethoxylation should generate a carbocation intermediate which is stabilized by the neighboring sulfur atom. In fact, nucleophilic substitution with arenes has been successfully achieved as shown in Scheme 6.7 [43], This procedure is useful for the preparation of trifluoroethyl aromatics. As already mentioned, generation of carbocations bearing an a-trifluoromethyl group is difficult due to the strong electron-withdrawing effect. Therefore, this carbon-carbon bond formation reaction is remarkable from both mechanistic and synthetic aspects. 

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]. 

For a review of sulfur nucleophiles in aromatic substitution, sec Peach, in Patai The Chemistry of the Thiol Group, pt. 2 Wiley New York. 1974, pp. 735-744. 

The cyclopentene annulations can also occur in the reactions of alkynyliodo-nium salts with nitrogen- and sulfur nucleophiles (Scheme 61). Specifically, azi-docyclopentene 155 is formed upon treatment of octynyliodonium tosylate 154 with sodium azide in dichloromethane [123]. The reaction of alkynyliodonium salt 156 with sodium toluenesulfinate results in the formation of substituted indene 157 via alkylidene carbene aromatic C-H bond insertion [124]. 

An important use of the traditional Skraup synthesis is to make 6-methoxy-8-nitroquinoline from an aromatic amine with only one free ortho position, glycerol, the usual concentrated sulfuric acid, and the oxidant arsenic pentoxide. Though the reported procedure uses 588 grams of As2Os, which might disconcert many chemists, it works well and the product can be turned into other quinolines by reduction of the nitro group, diazotization, and nucleophilic substitution (Chapter 23). 

Abstract Synthesis methods of various C- and /V-nitroderivativcs of five-membered azoles - pyrazoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazoles, oxazoles, oxadiazoles, isoxazoles, thiazoles, thiadiazoles, isothiazoles, selenazoles and tetrazoles - are summarized and critically discussed. The special attention focuses on the nitration reaction of azoles with nitric acid or sulfuric-nitric acid mixture, one of the main synthetic routes to nitroazoles. The nitration reactions with such nitrating agents as acetylnitrate, nitric acid/trifluoroacetic anhydride, nitrogen dioxide, nitrogen tetrox-ide, nitronium tetrafluoroborate, V-nitropicolinium tetrafluoroborate are reported. General information on the theory of electrophilic nitration of aromatic compounds is included in the chapter covering synthetic methods. The kinetics and mechanisms of nitration of five-membered azoles are considered. The nitroazole preparation from different cyclic systems or from aminoazoles or based on heterocyclization is the subject of wide speculation. The particular section is devoted to the chemistry of extraordinary class of nitroazoles - polynitroazoles. Vicarious nucleophilic substitution (VNS) reaction in nitroazoles is reviewed in detail. 

The nucleophilic substitution of chlorine in aromatic sulfur(II) and sulfur(IV) derivatives proceeds under lower temperature (- 25 C + 5 C). Apparently, in these reactions, a stoichiometric quantity of tris(dimcthylamino)sulfonium difluorotrimethylsilicate should be used, e.g. for formation of 33 and 34." ... 

Aromatic compounds substituted by electron-donating groups such as aniline, A-methylani-line, A/,A-dimethylaniline, phenol, anisole, and indole undergo nucleophilic addition across the N(3)-C(4) bond of quinazoline in 1 M sulfuric acid to give the corresponding 4-aryl-3,4-dihy-droquinazolines 20. ... 

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