Substitution, electrophilic with sulfur electrophiles

Experimental requirements for the isolation of these nitramino derivatives are developed in Ref. 87. They rearrange easily to ring nitro-substituted isomers (see Section V.6). In the 2-aminothiazole series, nitration may proceed through direct electrophilic substitution competing with rearrangement of nitramino derivatives. Dickey et al. have shown that the rearrangement proceeds rapidly in 96% sulfuric acid at 2(fC, but in 85% sulfuric add it is very slow so. according the concentration of add various mechanisms can participate in the formation of the 5-nitro derivative. 

The acid-catalyzed additions of bromide and chloride ion to thiiranes occurs readily, with halide preferentially but not exclusively attacking the most substituted carbon atom of the thiirane. The reaction of 1-substituted thiiranes with acetyl chloride shows a slight preference for halide attack at the less substituted carbon atom (80MI50601). For further discussion of electrophilic catalysis of halide ion attack see Section 5.06.3.3.2. The reaction of halogens with thiiranes involves electrophilic attack on sulfur (Section 5.06.3.3.6) followed by nucleophilic attack of halide ion on carbon. 

Reactivity toward nucleophiles and comparison with other electrophilic centers 152 Paths for nucleophilic substitution of sulfonyl derivatives 156 Direct substitution at sulfonyl sulfur stereochemistry 157 Direct substitution at sulfonyl sulfur stepwise or concerted 158 The elimination-addition path for substitution of alkanesulfonyl derivatives 166 Homolytic decomposition of a-disulfones 172 10 Concluding remarks 173 Acknowledgement 174 References 174... 

Except for these studies of their protonation behavior, almost the only other aspect of the chemistry of sulfonic acids that has been investigated to any extent from a mechanistic point of view is the desulfonation of aromatic sulfonic acids or sulfonates. Since this subject has been well reviewed by Cerfontain (1968), and since the reaction is really more of interest as a type of electrophilic aromatic substitution than as sulfur chemistry, we shall not deal with it here. One should note that the mechanism of formation of aromatic sulfonic acids by sulfonation of aromatic hydrocarbons has also been intensively investigated, particularly by Cerfontain and his associates, and several... 

In the reactions with phosphonio-a-methoxycarbonyl-alkanides, the products of type 261 derived from 1,3-cycloaddition can rearrange to the tautomeric lif-pyrazolo-triazole (87MI2). The reaction of 3-diazopyra-zoles and 3-diazoindazole with acyl-substituted phosphonium ylides led to pyrazolo-triazine and indazolo-triazine derivatives 266 instead of the expected triazole compounds (8IJHC675). In this case, the ylides, which can exist as phosphonium enolates, possess nucleophilic and electrophilic centers in a /8-relationship, giving [7 + 2] or [11 -I- 2]cycloaddition reactions. With dimethylsulfonio-a-aroyl-methanides, very complex, temperature-dependent mixtures were obtained, in some cases with sulfur retention (87MI3). 

The a-phenyl substituted six-membered sulfur-containing material 399 was reduc-tively cleaved using DTBB (5%) as the arene catalyst in THF at —78°C. The resulting intermediate 400 was then reacted with an electrophile followed by hydrolysis, yielding functionalized thiols 401 (Scheme 112) . 

The preferred position for electrophilic substitution in the pyridine ring is the 3 position. Because of the sluggishness of the reactions of pyridine, these are often carried out at elevated temperatures, where a free radical mechanism may be operative. If these reactions are eliminated from consideration, substitution at the 3 position is found to be general for electrophilic reactions of coordinated pyridine, except for the nitration of pyridine-N-oxide (30, 51). The mercuration of pyridine with mercuric acetate proceeds via the coordination complex and gives the anticipated product with substitution in the 3 position (72). The bromina-tion of pyridine-N-oxide in fuming sulfuric acid goes via a complex with sulfur trioxide and gives 3-bromopyridine-N-oxide as the chief product (80). In this case the coordination presumably deactivates the pyridine nucleus in the 2 and... 

Nitration of benzo[6]furan may be achieved with nitric acid in acetic acid and affords the 2-nitro compound, although nitrogen dioxide in benzene is reported to give the 3-nitro compound. 2-Phenylbenzo[6]furan with nitric acid in acetic acid yields the 3- and 6-nitro compounds. Treatment of 2-bromobenzo[6]furan with nitric acid and sodium nitrite yields 2-nitrobenzo[6]furan. The only electrophilic substitution reported with a benzo[c]furan is nitration of 1,3-diphenylbenzo[c ]furan with sodium nitrate and sulfuric acid, and this occurs on a phenyl group. 

The cis- and frans-sulfoxides (551) and (552) have been O-methylated with Meerwein s reagent. Reaction of the methoxy derivative with MeMgBr proceeds with inversion of configuration (Scheme 211) (74JA8026). The stereochemical course of the interconversions of sulfoxide, sulfimide and sulfoximide in the 2,3-dihydrobenzo[6]thiophene series has been investigated (73JA1916). The reaction cycle (Scheme 212) involves both nucleophilic and electrophilic substitution at chiral sulfur. Inversion of configuration takes place in the conversion of (553) to (554) in pyridine. 

Cyclopropanations of a,/i-unsaturated ketones with sulfur-substituted methylenes have been achieved in several ways using this methodology. Sequential treatment of conjugated enones with (PhS)3CLi,. s-BuLi and electrophiles produces phenylthiocyclopropanes (equation 128)275. Generation of lithium bicyclofl. 1,0]butane-2-olates as intermediates has... 

Carbon-sulfur bonds can be formed by electrophilic substitution of acetylacetonates with sulfur dichloride or thiocyanogen and the chlorosulfur group can be readily transformed by nucleophilic displacement of chloride ion (Scheme 72).285 236... 

In another study, Deno and Schriesheim (1955) assessed a set of substituent parameters through study of the ionization equilibria of substituted triarylmethanols in sulfuric acid (Deno et al., 1955). The authors asserted that it would be necessary to proceed with caution in the application of the constants because imprecise relationships between the parameters and other side-chain electrophilic reactions were observed. 

In spite of their reluctance to undergo electrophilic substitution, pyrazole hydrochlorides react under comparatively mild conditions (80-100°) with sulfur dichloride, sulfur monochloride, and even thionyl chloride to give sulfides (59).544 Earlier it was erroneously... 

Two of the reactions that are used in the industrial preparation of detergents are electrophilic aromatic substitution reactions. First, a large hydrocarbon group is attached to a benzene ring by a Friedel-Crafts alkylation reaction employing tetrapropene as the source of the carbocation electrophile. The resulting alkylbenzene is then sulfonated by reaction with sulfuric acid. Deprotonation of the sulfonic acid with sodium hydroxide produces the detergent. 

Electrophilic substitution in 12.2 indicates that the 7-position (corresponding to the p-position of naphthalene) is the more reactive, and this follows since this position is para conjugated with sulfur (12.8), whereas the 6-position is ortho conjugated (12.9). Yields are lower than in substitution of 12.1, but this does not necessarily indicate that 12.2 is less reactive, since substitution is accompanied by ring-contraction reactions. No quantitative data are yet available. 

Bis(phenylselanyl)methyllithiums 429 (R = H) are stable till 0 °C and were initially trapped with deuterium oxide, methyl iodide and benzophenone639. a-Substituted organolithium intermediate 429 (R = Me, w-CgH ), prepared with LiTMP in THF/HMPA at — 20 °C, reacted with alkyl bromides, ethylene oxide and benzaldehyde to give products 430 in good yields (Scheme 113)640. Bis(methylselanyl)methyllithiums 431 have been allowed to react with different electrophiles to afford products 432 (Scheme 113)640. Alkylated products have been deprotected with mercury(II) chloride or copper(II) chloride/copper(II) oxide, and by oxidation with hydrogen peroxide or benzeneseleninic anhydride644. Deprotection of selenoacetals to ketones can also be performed with sulfuric acid645. 

The nitration of 2-phenylindazole at 0°C with sulfuric-nitric acid mixture leads to 5-nitro-2-phenylindazole and 7-nitro-2-phenylindazole. These compounds have been identified using NMR spectroscopy [19]. In spite of the fact that the indazole positions 5 and 7 are most reactive with respect to electrophilic substitution [20] it is difficult to know beforehand the competition between the aromatic positions of the indazole ring (C-4, C-5, C-6, C-7) and the /V-phcnyl ring. 

---