The action of sulphur monochloride on aromatic primary amines: the Herz reaction

Abstract

1.3.2-Benzothiazathiolium chlorides are obtained by the action of sulphur monochloride on a primary aromatic amine, its salts, or N-acyl derivatives. Four reactions are involved, (i) the formation of the heterocyclic ring, (ii) the chlorination of the aromatic ring, (iii) replacement of electron-attracting groups in the orthoand para-positions by chlorine, and (iv) the oxidation of the sulphur atom in position 2. A likely sequence of reactions is considered, and experimental evidence is given in support of each stage. HERZ t found that a primary aromatic amine, its salts, or N-acyl derivatives, when heated with an excess of sulphur monochloride give a 1,3,2-benzothiazathiolium chloride provided that the amine has at least one unsubstituted ortho-position. An unsubstituted position para to the amino-group is simultaneously chlorinated. o-Toluidine, for example, gives (I; R1 = Me, R2 = Cl). R'Deactivating groups such as nitro-, carboxylic acid, sulphonic acid, or arsonic acid in the para-position are displaced by ch1orine.l The o-nitro-groups in 2-nitrot For a review of the Herz reaction see ref. 2.

Benzo[1,2,3]dithiazole Compounds: A History of Synthesis and Their Renewed Applicability in Materials and Synthetic Chemistry, Originating from the Herz Reaction

“…This reasoning represents a significant improvement in comprehension, and it was correct to deduce that S2Cl2 is not the direct source of the chloride, but it was still not understood how the chloride actually originated. This new hypothesis by Hope involving a free chloride ion undergoing nucleophilic substitution of a group on the ring, rather than electrophilic substitution by disulfur dichloride, is supported by results obtained when free Br2 was added to the reaction mixture during the Herz reaction resulting in the isolation of the Herz bromide salt as the product (Scheme 6) [22]. This led to the theory that the aromatic C-Cl bond forms not from reaction with S2Cl2 but with Cl2.…”

“…This is one of the first reports of a mechanistic investigation into the Herz reaction, and although the conclusions are limited, it was determined that this structure (Scheme 4, 2a) was not intermediate because it did not react under these conditions [16]. A subsequent study by Hope et al defines the Herz reaction in terms of three separate stages [22]. The stages were:…”

“…These compounds readily and reversibly react with water to form the sulfone structure 3 (faster in the presence of mild alkaline) and revert to the Herz chloride salt upon treatment with strong HCl [7]. The S-oxide 3 can be further manipulated to produce other structures [21]; the simplest way is to use alkaline hydrolysis, leading to ortho-aminothiophenols, as will be elaborated in detail subsequently [22]. Both the intermediate compounds and the final 2-aminothiophenol hydrolysis products have a variety of uses, but the objective cited by the literature at the time was to make scaffolds for use in the synthesis of dyes [19,23].…”

“…The initiating step involves the polarised S-Cl bonds, which ensures that the S atom is electrophilic and hence can be attacked by nucleophilic nitrogen. However, additional speculation that the aromatic chlorination occurs by the action of sulphur monochloride (S E Ar) was found to be inaccurate, and there was no account for the fact that electron-withdrawing groups in this position were replaced by a chloride [22]. Although, in general, this proposed sequence proved helpful in explaining many of the experimental results, it was but a beginning to the full understanding of the sequence.…”

“…(3) Oxidation of the thiophenol sulphur to form the salt. Interestingly, they discovered that free chlorine (Cl2) was present in the reaction and deduced that this was more likely to be the chlorinating agent for the ring, as sulphur monochloride is not sufficiently electrophilic (at the chlorides) to act as a powerful chlorinating agent [22]. They also concluded that the chlorination stage cannot occur after the Herz salt 2 has already formed, as previously suggested by Huetis, because the azathio- A subsequent study by Hope et al defines the Herz reaction in terms of three separate stages [22].…”