Transition‐Metal‐Free C‐S Bond Forming Strategy towards Synthesis of Highly Diverse Pyrazole Tethered Benzothiazoles: Investigation of their Photophysical Properties

Abstract

A metal-free domino approach has been devised towards construction of two CÀ S bonds for the synthesis of bioactive N, S-heterocycles. The developed method was extended for the preparation of structurally diverse pyrazole tethered benzothiazole frameworks by using one-pot operation of pyrazole C-3/4/5 carbaldehydes, electron rich aromatic amines and elemental sulfur. This protocol provides excellent fluorophores with several additional advantages such as transition metal-free approach, inexpensive and odorless sulfur source, superior atom economy, and broad substrate scope including gram scale synthesis. The synthesized pyrazole tethered benzothiazole fluorophores were evaluated for their luminescent properties including absorbance, excitation, emission, molar extinction coefficient, brightness, and Stokes shift. The photophysical studies revealed that these pyrazole and benzothiazole hybrids emerged as excellent fluorophores and could exhibit fluorescence quantum yield up to 66%.

Facile synthesis of substituted 2-aroylbenzo[b]thiophen-3-ols to form novel triazole hybrids using click chemistry

“…To further extend the scope of a 2-aroyl-benzo[b]thiophen-3-ol substrate (5), we introduced an alkyne moiety at the 3hydroxy position, conducted a click reaction, and prepared novel benzothiophene-triazole hybrids. We believe that this robust method for the direct synthesis of 5 starting from 2-mercaptobenzoic acid (6) under basic conditions will complement the previously reported method under acidic conditions. 33 The core 2-aroyl-benzo[b]thiophen-3-ol (5) structure has been synthesized previously from 2-mercaptobenzoic acid (6) using a 2 or 3-step-long reaction sequence and/or using harsh conditions as shown in Scheme 1.…”

“…For the optimization of the reaction, we used 2-mercaptobenzoic acid (6) and phenacyl bromide (8a) as model substrates. By screening different inorganic and organic bases, reaction solvents, reaction times, and temperatures, the formation of acyclic product 9a and the targeted benzo[b]thiophenes (5a) were observed as shown in Table 1.…”

“…4,5 Among them, sulfur-containing heterocycles are gaining attention in organic synthesis due to their applications in materials sciences, pharmaceutical industries, and food chemistry. 6,7 Benzo[b]thiophene is a versatile sulfur-containing heterocyclic scaffold, which frequently appears in pharmaceutically interesting compounds with a diverse range of biological activities. [8][9][10][11][12] For instance, various drugs including raloxifene (1), arzoxifene (2), rintodestrant (3), and LSZ102 (4) feature the benzo[b]thiophene core and are currently clinically utilized for the treatment of estrogen-receptor-positive breast cancer (Fig.…”

“…We envision that the 2-aroylbenzo[b]thiophen-3-ol core could provide access to diverse benzo[b]thiophene analogs for discovering new SERMs/SERDs. To extend our efforts on the discovery of early-phase inhibitor leads for developing antiviral and anticancer drugs, [29][30][31][32] we herein report a simple, one-pot synthetic method for the preparation of substituted 2-aroyl-benzo[b]thiophen-3-ol derivatives (5a-s) by reacting 2-mercaptobenzoic acid (6) with substituted aryl bromomethyl ketones (8a-s) in the presence of triethylamine in DMF. To further extend the scope of a 2-aroyl-benzo[b]thiophen-3-ol substrate (5), we introduced an alkyne moiety at the 3hydroxy position, conducted a click reaction, and prepared novel benzothiophene-triazole hybrids.…”

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

“…Although, these protocols are useful and have exhibited wide applications in organic synthesis (Figure 2), the scope of these reported methods may suffer from drawbacks such as harsh reaction conditions, use of expensive reagents, prolonged reaction times, low product yields, and cumbersome product isolation procedures [58][59][60][61][62]. In the recent past, our group also reported two methods towards the exploration of elemental sulfur for the formation of a sulfur-containing framework; however, these methods suffer from some drawbacks such as lack of diversity in starting substrate, need of base/catalyst and limitation of starting reagents [63,64]. Our current work was completed with the exploration of the position of the pyrazole ring like C-3, C-4 and C-5 and we also employed the pyrazole-based AXB3s (4-iodo-C-3 and 4-iodo-C-5).…”