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

Abstract

The benzo[1,2,3]dithiazole is a unique heteroaromatic functionality whose conjugated profile instils some fascinating electronic properties. This has been historically recognized in the design and manufacture of organic dyes early last century. Although, with the benefit of increased diagnostic techniques and improved understanding, these structures are attracting greater attention in additional research settings, including applications as organic radicals and semiconductors. In addition, the benzodithiazole functionality has been shown to be a valuable synthetic intermediate in the preparation of a variety of other privileged aromatic and heteroaromatic targets, many of which are important APIs. In this review, the authors aim to critically analyse the potential applicability of these compounds to the fields of not only small-scale laboratory synthetic and medicinal chemistry but also commercial-scale processes and increasingly materials chemistry.

4,4’-(Pyridin-4-ylmethylene)dibenzonitrile

“…However, the presence and positioning of a halogen-substituent (in particular, fluoro), combined with other electron withdrawing groups on an aromatic ring can arise to create an effective alternative electrophilic site. While this method is frequently utilised to form aromatic C-heteroatom bonds [8][9][10][11], the formation of C-C without any additional form of metal catalysis remains fairly unique.…”

“…However, the presence and positioning of a halogen-substituent (in particular, fluoro), combined with other electron withdrawing groups on an aromatic ring can arise to create an effective alternative electrophilic site. While this method is frequently utilised to form aromatic Cheteroatom bonds [8][9][10][11], the formation of C-C without any additional form of metal catalysis remains fairly unique. As encountered in our work, upon deprotonation of the methylpyridine (1) starting material, the formed carbanion can competitively attack instead the aryl electron deficient 2 of 5 centre of the 4-fluorobenzonitrile (2) acceptor (Figure 2).…”

6-Chloro-3H-benzo[d][1,2,3]dithiazol-2-ium Chloride

“…The Herz reaction is a remarkable transformation for its ability to not only introduce an ortho-sulfur to an aniline ring, but also activate it to nucleophilic attack at the 4-position (via the introduced chloride); it is surprising that only a handful of publications have made use of this unique feature [11,12]. The following mechanism (Scheme 3) was recently proposed and published, aiming to take into account the literature results as well as the data collected in this study [6]. The consequences of the mechanism include the consumption of an excess of disulfur dichloride, although the precise extent of this is unclear.…”

“…Interestingly, for compound 3 the major observed ion (Figure 4) does not correspond to the expected structure, but instead to a structure such as 2c (Figure 3). The following mechanism (Scheme 3) was recently proposed and published, aiming to take into account the literature results as well as the data collected in this study [6]. The consequences of the mechanism include the consumption of an excess of disulfur dichloride, although the precise extent of this is unclear.…”

“…Research into the chemistry and properties of the benzo [1,2,3]dithiazole structures, produced generally by the Herz reaction, have historically centred around their utilisation as dyes and, by extension, as medicinal building-blocks [1,2]. More recent investigations have concerned their unusual electron properties, including generation of stable radicals and their solid-state material properties [3][4][5][6]. Being a heterocycle of general interest [7][8][9][10][11][12][13], we considered it of value for exploring the scaled preparation of this compound optimising the outline syntheses collated from various literature sources.…”