Recent Advances in Synthesis of Benzothiazole Compounds Related to Green Chemistry

molecules

Review Recent Advances in Synthesis of Benzothiazole Compounds Related to Green Chemistry

Xiang Gao 1,*, Jiao Liu 1, Xin Zuo 1, Xinyue Feng 1 and Ying Gao 2,*

1 College of Geology and Environment, Xi’an University of Science and Technology, Xi’an 710054, China; [email protected] (J.L.); [email protected] (X.Z.); [email protected] (X.F.) 2 Department of Teaching Quality Evaluation, Yan’an University, Yan’an 716000, China * Correspondence: [email protected] (X.G.); [email protected] (Y.G.); Tel.:+86-177-2950-5365 (X.G.); +86-158-2911-7319 (Y.G.) Academic Editors: Brindusa Tiperciuc, Cristina Nastasă and Ioana Ionut, Received: 16 March 2020; Accepted: 2 April 2020; Published: 5 April 2020

Abstract: Benzothiazoles have played an important role in the ﬁeld of biochemistry and medicinal chemistry due to their highly pharmaceutical and biological activity. The development of synthetic processes is undoubtedly one of the most signiﬁcant problems facing researchers. In this review paper, we provided recent advances in the synthesis of benzothiazole compounds related to green chemistry from condensation of 2-aminobenzenethiol with aldehydes/ketones/acids/acyl chlorides and the cyclization of thioamide or carbon dioxide (CO2) as raw materials, and the future development trend and prospect of the synthesis of benzothiazoles were anticipated.

Keywords: benzothiazoles; 2-aminobenzenethiol; green chemistry; condensation; cyclization; thioamide; CO2

1. Introduction Benzothiazole is a representative class of sulfur-containing heterocycles and involves a benzene ring fused to a thiazole ring. The benzothiazole ring system was originally found in various marine and terrestrial natural compounds, which is widely used as vulcanization accelerators, antioxidants, plant growth regulators, anti-inflammatory agents, enzyme inhibitors, imaging reagents, fluorescence materials, and electroluminescent devices due to its highly pharmaceutical and biological activity [1–4]. Especially, benzothiazole plays an important role in the field of medicinal chemistry and renders an extensive range of biological activities including anti-cancer [5,6], anti-bacterial [7,8], anti-tuberculosis [9,10], anti-diabetic [11], anthelmintic [12], anti-tumor [13–15], anti-viral [16,17], anti-oxidant [18], anti-inflammatory [19,20], anti-glutamate and anti-parkinsonism [21], anticonvulsant [22], muscle relaxant activities [23], neuroprotective [24], inhibitors of several enzymes and so on [25]. Hence, the synthesis of benzothiazoles is of considerable interest due to their potent and significant biological activities and great pharmaceutical value. Different synthetic paths have been developed for the preparation of benzothiazole derivatives (Scheme1). Among them, the condensation reaction of 2-aminobenzenethiol with a carbonyl or cyano group-containing substance is the most commonly used method (Scheme1, Method 1) [ 26,27]. Riadi and co-workers [28] found that benzothiazoles could be synthesized from the condensation of 2-aminobenzenethiol and aromatic aldehydes in refluxing toluene at 110 ◦C. Sun and co-workers [29] reported a copper-catalyzed method for the formation of 2-substituted benzothiazoles via condensation of 2-aminobenzenethiols with nitriles. Moreover, many researchers found that benzothiazoles could also be synthesized by the reaction of ortho-halogenated aniline with isothiocyanates, carbon disulfide and piperidine, aldehydes and sulfur, carbon disulfide and thiol, acid chloride and Lawesson’s reagent (Scheme1, Method 2) [ 30–34]. In addition, an alternative method is the intramolecular cyclization of

Molecules 2020, 25, 1675; doi:10.3390/molecules25071675 www.mdpi.com/journal/molecules Molecules 2020,, 2525,, 1675x 2 of 1617

method is the intramolecular cyclization of ortho-halogenated analogs (Scheme 1, Method 3) [35,36]. ortho-halogenatedSahoo and colleagues analogs [37] (Scheme indicated1, Method that 3) [ benzothiazoles35,36]. Sahoo and could colleagues be synthesized [37] indicated from that benzothiazolesortho-halothioureas could using be synthesized both Cu(I) from and ortho-halothioureasPd(II) transition metal using as a both catalyst. Cu(I) Unfortunately, and Pd(II) transition these metaltraditional as a catalyst.processes Unfortunately,have some disadvantages, these traditional such processesas low yield, have poor some selectivity, disadvantages, harsh reaction such as lowconditions, yield, poor the use selectivity, of toxic harshreagents reaction or metal conditions, catalysts, the etc. use However, of toxic reagentsgreen chemistry or metal advocates catalysts, etc.for However,the use of greenchemical chemistry technologies advocates and for methods the use ofto chemicalreduce or technologies stop the use and and methods production to reduce of raw or stopmaterials, the use catalysts, and production solvents of rawand materials,reagents, catalysts,products solventsor by-products and reagents, that productsare harmful or by-products to human thathealth, are harmfulcommunity to human safety, health, and communitythe ecological safety, environment. and the ecological Therefore, environment. an exploration Therefore, anof explorationenvironmentally of environmentally friendly synthetic friendly routes synthetic to prepare routes benzothiazoles to prepare benzothiazoles is highly desirable. is highly desirable.

Scheme 1. The common synthetic routesroutes for benzothiazoles.

In recentrecent years,years, with the continuous development of green chemistry concepts for thethe environmental protection [[38,39]38,39] andand resourceresource utilizationutilization [[40–42],40–42], thethe developmentdevelopment ofof metal-freemetal-free catalysts, the use of renewable reaction materials and reagents, and the realization of reactions under mild conditionsconditions havehave attractedattracted researchers’researchers’ attention.attention. Notably, various environmentally friendly pathways have been been discovered discovered for for the the synthesis synthesis ofof benzothiazoles benzothiazoles in inthe the past past decades. decades. Here, Here, the thepresent present article article is intended is intended to tobriefly briefly review review rece recentnt research research progress progress concerning concerning the the synthesis of benzothiazoles compounds,compounds, which which mainly includesmainly theincludes condensation the reactioncondensation of 2-aminobenzenethiol reaction of and2-aminobenzenethiol aldehydes/ketones and/acids aldehydes/ketones/acids/acyl/acyl chlorides. In addition, chlorides. the cyclization In addition, of thioamides the cyclization offered of benzothiazolethioamides offered derivatives. benzothiazole Moreover, derivatives. a series of More benzothiazoleover, a series compounds of benzothiazole were also compounds synthesized were by cyclizationalso synthesized of CO by2 as cyclization raw materials. of CO2 as raw materials. 2. Synthesis of Benzothiazoles 2. Synthesis of Benzothiazoles 2.1. By Condensation Reaction 2.1. By Condensation Reaction 2.1.1. Condensation of 2-Aminothiophenol with Aldehydes 2.1.1. Condensation of 2-Aminothiophenol with Aldehydes 2-bisthiophene substituted benzothiazole products obtained from the condensation of 2-aminobenzenethiol2-bisthiophene withsubstituted 5-aldehyde benzothiazole bisthiophene products compounds obtained at the presencefrom the of dimethylcondensation sulfoxide of (DMSO)2-aminobenzenethiol under reflux conditionswith 5-aldehyde for 1 h wasbisthiophe pointedne out compounds by Batista andat the co-authors presence (Scheme of dimethyl2)[ 43]. Thesulfoxide evaluation (DMSO) of the under fluorescence reflux conditions properties for of products 1 h was was pointed carried out out. by They Batista have and shown co-authors strong fluorescence(Scheme 2) [43]. in the The 450–600 evaluation nm region,of the fluorescence as well ashigh properties quantum of products yields and was large carried Stokes’ out. shifts.They Duehave toshown their strong strong fluorescence fluorescence, in the these 450–600 compounds nm region, described as well above as high could quantum find yields applications and large as fluorescentStokes’ shifts. markers. Due to their strong fluorescence, these compounds described above could find applications as fluorescent markers.

Molecules 2020, 25, 1675x 3 of 17 16 Molecules 2020, 25, x 3 of 17 Molecules 2020, 25, x 3 of 17

Scheme 2. Condensation of 2-aminobenzenethiol with 5-aldehyde bisthiophene compounds. Scheme 2. Condensation of 2-aminobenzenethiol with 5-aldehyde bisthiophene compounds. Scheme 2. CondensationCondensation of of 2-aminobenzenethiol 2-aminobenzenethiol with 5-aldehyde bisthiophene compounds. A series of benzothiazole compounds with different substituents were efficiently synthesized by A series of of benzothiazole benzothiazole compounds compounds with with different diﬀerent substituents substituents were were efficiently eﬃciently synthesized synthesized by Guo Aand series co-authors of benzothiazole [44] from compounds the condensation with different of 2-aminothiophenol substituents were andefficiently aldehydes synthesized and their by Guoby Guo and and co-authors co-authors [44] [44 from] from the the condensation condensation of of 2-aminothiophenol 2-aminothiophenol and and aldehydes aldehydes and and their Guoderivatives and co-authors using a mixture [44] fromof H2 Othe2/HCl condensation as a catalyst ofin ethanol2-aminothiophenol at room temperature and aldehydes for 1 h (Scheme and their 3). derivatives using using a a mixture mixture of of H 22OO22/HCl/HCl as as a a catalyst catalyst in in ethanol ethanol at at room room temperature temperature for for 1 1 h h (Scheme (Scheme 3).3). derivativesFor a comparative using a mixturestudy, aof ratio H2O 2of/HCl 1:1:6:3 as a ofcatalyst 2-aminothiophenol/aromatic in ethanol at room temperature aldehyde/H for 1 h2O (Scheme2/HCl was 3). For a comparative study, a ratioratio ofof 1:1:6:31:1:6:3 ofof 2-aminothiophenol2-aminothiophenol/aromatic/aromatic aldehydealdehyde/H/H22O2/HCl/HCl was Forfound a comparative to be optimum study, for a theratio coupling. of 1:1:6:3 Furtherm of 2-aminothiophenol/aromaticore, both aldehydes bearing aldehyde/H electron-donating2O2/HCl was foundfound to be optimumoptimum forfor thethe coupling.coupling. Furtherm Furthermore,ore, both aldehydes bearing electron-donating foundsubstituents to be optimumand electron-withd for the coupling.rawing Furthermsubstituentsore, bothcould aldehydes be used bearing to obtain electron-donating the desired substituentssubstituents andand electron-withdrawing electron-withdrawing substituents substituents could becould used be to obtainused theto desiredobtain benzothiazolesthe desired substituentsbenzothiazoles and in excellentelectron-withd yields byrawing this method. substituents Short reactioncould time,be used easy andto quickobtain isolation the desired of the benzothiazolesin excellent yields in excellent by this method. yields by Short this method. reaction time,Short easyreaction and time, quick easy isolation and quick of the isolation products, of andthe benzothiazolesproducts, and excellent in excellent yields yields are bythe this main method. advantages Short ofreaction this procedure. time, easy and quick isolation of the products,excellent yieldsand excellent are the mainyields advantages are the main of advantages this procedure. of this procedure. products, and excellent yields are the main advantages of this procedure.

Scheme 3. Condensation of 2-aminothiophenol and aldehydes at room temperature. SchemeScheme 3. 3. CondensationCondensation of of 2-aminothiophenol 2-aminothiophenol and and aldehydes aldehydes at at room room temperature. Scheme 3. Condensation of 2-aminothiophenol and aldehydes at room temperature. Kumar et al. [[45]45] foundfound thatthat polystyrenepolystyrene polymerpolymer catalysts grafted with iodine acetate could Kumar et al. [45] found that polystyrene polymer catalysts grafted with iodine acetate could promoteKumar the et eefficiental.fficient [45] found condensationcondensation that polystyrene ofof 2-aminobenzenethiol2-amin polymerobenzenethiol catalysts and grafted benzaldehyde with iodine compounds acetate could in promote the efficient condensation of 2-aminobenzenethiol and benzaldehyde compounds in promotedichloromethane the efficient to synthesize condensation benzothiazole of 2-amin comp compoundsobenzenethiolounds (Scheme and4 4). ).benzaldehyde TheThe catalystcatalyst was wascompounds synthesizedsynthesized in dichloromethane to synthesize benzothiazole compounds (Scheme 4). The catalyst was synthesized dichloromethaneaccording to an eefficient ffitocient synthesize procedure benzothiazole and was used comp inounds the combinatorial (Scheme 4). The synthesis catalyst of was benzimidazoles, synthesized according to an efficient procedure and was used in the combinatorial synthesis of benzimidazoles, whichaccording gave to the an benefitsbenefitsefficient of procedure solid support and was and theused extra in the advantage combinatorial of the diversitysynthesis notof benzimidazoles, being lost in the which gave the benefits of solid support and the extra advantage of the diversity not being lost in the whichlibraries gave from the any benefits point of as solid in thethe support casecase ofof and earlierearlier the reports.reextraports. advantage Furthermore, of the afterdiversity the reaction, not being the lost catalyst in the libraries from any point as in the case of earlier reports. Furthermore, after the reaction, the catalyst waslibraries converted from any to polymer-supported point as in the case iodobenzene,of earlier reports. which Furthermore, was recovered after by the filtration,filtration, reaction, converted the catalyst to was converted to polymer-supported iodobenzene, which was recovered by filtration, converted to waspoly[4-diacetoxyiodo] converted to polymer-supported styrene (PDAIS)(PDAIS) iodobenzene, andand reused.reused. Thiswhich reusing was recovered could be doneby filtration, many times converted without to poly[4-diacetoxyiodo] styrene (PDAIS) and reused. This reusing could be done many times without poly[4-diacetoxyiodo]loss of activity of the catalyst. styrene (PDAIS) and reused. This reusing could be done many times without loss of activity of the catalyst. loss of activity of the catalyst.

Scheme 4. Condensation of 2-aminobenzenethiol andand benzaldehyde compounds for 5–105-10 min. Scheme 4. Condensation of 2-aminobenzenethiol and benzaldehyde compounds for 5-10 min. Scheme 4. Condensation of 2-aminobenzenethiol and benzaldehyde compounds for 5-10 min. Maleki and co-authors [46] found that NH4Cl could catalyze the reaction of 2-aminothiophenol Maleki and co-authors [46] found that NH4Cl could catalyze the reaction of 2-aminothiophenol withMaleki benzaldehyde. and co-authors Especially, [46] benzothiazolefound that NH could4Cl could be obtained catalyze atthe a highreaction yield of by2-aminothiophenol this reacting in a with Malekibenzaldehyde. and co-authors Especially, [46] benzothiazolefound that NH could4Cl could be obtained catalyze at the a highreaction yield of by 2-aminothiophenol this reacting in a with benzaldehyde. Especially, benzothiazole could be obtained at a high yield by this reacting in a withmethanol-water benzaldehyde. mixedmixed Especially, solventsolvent at atbenzothiazole room room temperature temperatur coulde forbe for 1obtained h1 (Schemeh (Scheme at 5a). high Furthermore,5). Furthermore, yield by this the reacting studythe study of in the of a methanol-watermechanism showed mixed that solvent NH4Cl at activated room temperatur benzaldehydee for through 1 h (Scheme hydrogen 5). Furthermore, bonding and promotedthe study theof methanol-waterthe mechanism mixedshowed solvent that atNH room4Cl activatedtemperatur benzaldehydee for 1 h (Scheme through 5). Furthermore, hydrogen bonding the study and of thenucleophilic mechanism attack showed of benzaldehyde that NH4Cl by activated the amino benzaldehyde group of 2-aminobenzenethiol through hydrogen to obtain bonding the target and thepromoted mechanism the nucleophilic showed that attack NH of4Cl benzaldehyde activated benzaldehyde by the amino thgrouprough of hydrogen 2-aminobenzenethiol bonding and to promoted the nucleophilic attack of benzaldehyde by the amino group of 2-aminobenzenethiol to promotedproduct.obtain the Obviously, thetarget nucleophilic product. this method attackObviously, is aof reaction benzaldehyde this pathmeth thatod by compliesis the a reactionamino with group greenpath ofthat chemistry 2-aminobenzenethiol complies for thewith synthesis green to obtain the target product. Obviously, this method is a reaction path that complies with green obtainofchemistry benzothiazole the fortarget the and product.synthesis its derivatives Obviously,of benzothiazole due this to short meth and reactionod it s isderivatives a time, reaction high due yield,path to that andshort acomplies recyclablereaction withtime, catalyst. green high chemistry for the synthesis of benzothiazole and its derivatives due to short reaction time, high chemistryyield, and afor recyclable the synthesis catalyst. of benzothiazole and its derivatives due to short reaction time, high yield, and a recyclable catalyst. yield, and a recyclable catalyst.

Molecules 2020, 25, x 4 of 17 Molecules 2020, 25, x 4 of 17 Molecules 2020, 25, 1675 4 of 16 Molecules 2020, 25, x 4 of 17 Molecules 2020, 25, x 4 of 17

Scheme 5. Condensation of 2-aminobenzenethiol and benzaldehydes at room temperature. Scheme 5. Condensation of 2-aminobenzenethiol and benzaldehydes at room temperature. Scheme 5. Condensation of 2-aminobenzenethiol and benzaldehydes at room temperature. PraveenScheme et al. 5. Condensation[47]Condensation found that of of 2-aminobenzenethiol 2-aminobenzenethiolthe microwave conditions an andd benzaldehydes could effectively at room promote temperature. the synthesis Praveen et al. [47] found that the microwave conditions could effectively promote the synthesis of benzothiazole using phenyl iodoniumbis(triuoroacetate) (PIFA) as an oxidation reagent for the of benzothiazolePraveen et al. using [[47]47] foundphenyl that iodoniumbis(triuoroa the microwave conditionsconditionscetate) (PIFA)could effectively e ﬀasectively an oxidation promote reagent the synthesis for the condensationPraveen et reactional. [47] found of 2-aminobenzenethiol that the microwave co andnditions benzaldehyde could effectively compounds promote the(Scheme synthesis 6). ofcondensation benzothiazole reaction using phenyl of 2-aminobenzenethiol iodoniumbis(triuoroa iodoniumbis(triuoroacetate) andcetate) benzaldehyde (PIFA) (PIFA) as an compounds oxidation reagent (Scheme for the6). ofCompared benzothiazole with the using traditional phenyl heatingiodoniumbis(triuoroa method, the usagecetate) of (PIFA)a microwave as an oxidationcould reduce reagent the reaction for the condensationCompared with reactionreaction the traditional of 2-aminobenzenethiolof 2-aminobenzenethiol heating method, and the benzaldehyde andusage benzaldehyde of a microwave compounds compounds could (Scheme reduce 6).(Scheme the Compared reaction 6). condensationtime, improve thereaction reaction of yield,2-aminobenzenethiol and expand the universality and benzaldehyde of the substrate. compounds (Scheme 6). withCompared the traditional with the heating traditional method, heating the method, usage of athe microwave usage of a could microwave reduce thecould reaction reduce time, the improvereaction Comparedtime, improve with the the reaction traditional yield, heating and ex method,pand the the universality usage of a of microwave the substrate. could reduce the reaction time,the reaction improve yield, the reaction and expand yield, the and universality expand the of universality the substrate. of the substrate. time, improve the reaction yield, and expand the universality of the substrate.

Scheme 6. Condensation of 2-aminobenzenethiol and benzaldehydes under microwave irradiation. Scheme 6. Condensation of 2-aminobenzenethiol and benzaldehydes under microwave irradiation. Scheme 6. CondensationCondensation of of 2-aminobenzenethiol 2-aminobenzenethiol and benzaldehydes under microwave irradiation. YeScheme and 6.co-workers Condensation [48] of have2-aminobenzenethiol proposed a visi andble-light-promoted benzaldehydes under synthesis microwave of irradiation.benzothiazoles Ye andand co-workersco-workers [ 48[48]] have have proposed proposed a visible-light-promoted a visible-light-promoted synthesis synthesis of benzothiazoles of benzothiazoles from fromYe 2-aminothiophenols and co-workers [48] and havealdehydes proposed (Scheme a visi 7).ble-light-promoted The reaction system synthesis was irradiated of benzothiazoles with a 12W 2-aminothiophenolsfromYe 2-aminothiophenols and co-workers and aldehydes[48] and havealdehydes proposed (Scheme (Scheme7 ).a Thevisi 7).ble-light-promoted reaction The reaction system system was synthesis irradiated was irradiated of with benzothiazoles awith 12W a blue12W fromblue 2-aminothiophenolsLED for 6 h under andan air aldehydes atmosphere. (Scheme In orde 7). Ther to reaction explore system the universality was irradiated of this with reaction a 12W fromLEDblue forLED2-aminothiophenols 6 hfor under 6 h anunder air atmosphere. andan air aldehydes atmosphere. In order (Scheme toIn exploreorde 7). Ther to the reaction explore universality system the universality of was this irradiated reaction of conditionthis with reaction a 12W for bluecondition LED forfor different6 h under substrates, an air atmosphere. a series of alIndehydes order to were explore investigated, the universality and the ofresults this reactionshowed bluediconditionfferent LED substrates, forfor different6 h under a seriessubstrates, an ofair aldehydes atmosphere. a series wereof alIndehydes investigated,order to were explore andinvestigated, thethe resultsuniversality and showed the ofresults thatthis aromatic, reactionshowed conditionthat aromatic, for different heteroaromatic, substrates, and a seriesaliphatic of alaldedehydeshydes wereare applicable investigated, in theand transformation. the results showed The conditionheteroaromatic,that aromatic, for different heteroaromatic, and aliphatic substrates, aldehydes and a seriesaliphatic are of applicable alaldedehydeshydes in wereare the transformation.applicable investigated, in theand The transformation. the finding results off showedered The an thatfinding aromatic, offered heteroaromatic, an efficient, absenceand aliphatic of transition-metal aldehydes are applicablecatalysts and in theextra transformation. additive, and The a thatefindingfficient, aromatic, offered absence heteroaromatic, ofantransition-metal efficient, absenceand catalystsaliphatic of transition-metal and alde extrahydes additive, are applicablecatalysts and a convenientand in theextra transformation. synthetic additive, approach and The a findingconvenient offered synthetic an efficient,approach toabsence benzothiazoles. of transition-metal catalysts and extra additive, and a findingtoconvenient benzothiazoles. offered synthetic an efficient,approach toabsence benzothiazoles. of transition-metal catalysts and extra additive, and a convenient synthetic approach to benzothiazoles. convenient synthetic approach to benzothiazoles.

Scheme 7. Condensation of 2-aminothiophenols with aldehydes under visible light. Scheme 7. Condensation of 2-aminothiophenols with aldehydes under visible light. Scheme 7. Condensation of 2-aminothiophenols with aldehydes under visible light. MaphuphaScheme and 7. co-authors Condensation [49] [49 of] have2-aminothiophenols successfullysuccessfully developed with aldehydes a simple under and visible eefficientﬃ light.cient method for Maphupha and co-authors [49] have successfully developed a simple and efficient method for the synthesis Maphupha of of 2-arybenzothiazoleand 2-arybenzothiazole co-authors [49] derivatives derivativeshave successfull in in a agoody good developed to to excellent excellent a simple yield yield fromand from efficientthe the condensation condensation method for of the synthesisMaphupha of 2-arybenzothiazoleand co-authors [49] derivatives have successfull in a goody developed to excellent a simple yield fromand efficientthe condensation method for of theof2-aminothiophenol 2-aminothiophenol synthesis of 2-arybenzothiazole with with a series a series of derivatives of aryl-aldehydes aryl-aldehydes in a good using using to anexcellent an inexpensive inexpensive yield fromcommercial commercial the condensation laccase laccase as of a the2-aminothiophenol synthesis of 2-arybenzothiazole with a series of derivatives aryl-aldehydes in a good using to an excellent inexpensive yield fromcommercial the condensation laccase as of a 2-aminothiophenolcatalyst at room temperature with a series (Scheme(Scheme of aryl-aldehydes8 8).). using an inexpensive commercial laccase as a 2-aminothiophenolcatalyst at room temperature with a series (Scheme of aryl-aldehydes 8). using an inexpensive commercial laccase as a catalyst at room temperature (Scheme 8). catalyst at room temperature (Scheme 8).

Scheme 8. 8. CondensationCondensation of 2-aminothiophenol of 2-aminothiophenol with aryl-aldehydes with aryl-aldehydes catalyzed catalyzedby the commercial by the Scheme 8. Condensation of 2-aminothiophenol with aryl-aldehydes catalyzed by the commercial commerciallaccases. laccases. Scheme 8. Condensation of 2-aminothiophenol with aryl-aldehydes catalyzed by the commercial Schemelaccases. 8. Condensation of 2-aminothiophenol with aryl-aldehydes catalyzed by the commercial laccases.Merroun et al. [50] have reported an eﬃcient, easy, and green method for the benzothiazoles laccases.Merroun et al. [50] have reported an efficient, easy, and green method for the benzothiazoles synthesisMerroun by a et condensation al. [50] have reaction reported of an 2-aminothiophenol efficient, easy, and with green various method aromatic for the aldehydes benzothiazoles using synthesisMerroun by a etcondensation al. [50] have reaction reported of an 2-aminot efficient,hiophenol easy, and with green various method aromatic for the aldehydes benzothiazoles using SnPsynthesis2MerrounO7 as by a newa etcondensation al. heterogeneous [50] have reaction reported catalyst of an 2-aminot (Scheme efficient,9hiophenol). easy, In this and work, with green thevarious method high aromatic yields for (87–95%)the aldehydes benzothiazoles and using very synthesisSnP2O7 as bya new a condensation heterogeneous reaction catalyst of (Scheme2-aminot 9).hiophenol In this work, with variousthe high aromatic yields (87–95%) aldehydes and using very synthesisshortSnP2O reaction7 as bya new a timescondensation heterogeneous (8–35 min) reaction werecatalyst obtained;of (Scheme2-aminot meanwhile, 9).hiophenol In this work, thewith new variousthe catalyst high aromatic yields could (87–95%) bealdehydes reused and at using leastvery SnPﬁve2 timesO7 as a and new without heterogeneous any degradation catalyst of(Scheme its activity. 9). In this work, the high yields (87–95%) and very SnP2O7 as a new heterogeneous catalyst (Scheme 9). In this work, the high yields (87–95%) and very

Molecules 2020, 25, x 5 of 17

Molecules 2020, 25, x 5 of 17 Moleculesshort reaction 2020, 25 ,times x (8–35 min) were obtained; meanwhile, the new catalyst could be reused at5 least of 17 Molecules 2020, 25, x 5 of 17 five times and without any degradation of its activity. short reaction times (8–35 min) were obtained; meanwhile, the new catalyst could be reused at least short reaction times (8–35 min) were obtained; meanwhile, the new catalyst could be reused at least fiveshort times reaction and timeswithout (8–35 any min) degradation were obtained; of its activity. meanwhile, the new catalyst could be reused at least Moleculesfive times2020 and, 25, without 1675 any degradation of its activity. 5 of 16 five times and without any degradation of its activity.

Scheme 9. Condensation of 2-aminothiophenol with aromatic aldehydes.

Scheme 9. Condensation of 2-aminothiophenol with aromatic aldehydes. Bhat and co-authorsScheme 9. [51] Condensation have investigated of 2-aminothiophe the rapidnol synthesiswith aromatic of 2-aryl-benzothia/(oxa)zolesaldehydes. Scheme 9. Condensation of 2-aminothiophe 2-aminothiophenolnol with aromatic aldehydes. by the condensation of 2-aminothiophenol and diverse aryl aldehydes in the presence of Acacia Bhat and co-authors [51] have investigated the rapid synthesis of 2-aryl-benzothia/(oxa)zoles concinnaBhat andandas a co-authors co-authorsbiocatalyst [51[51] under] have have investigatedmicrowave investigated theirradiation the rapid rapid synthesis synthesis(Scheme of 10). 2-aryl-benzothiaof 2-aryl-benzothia/(oxa)zoles In comparison/(oxa)zoles with the by by theBhat condensation and co-authors of 2-aminothiophenol [51] have investigated and diversethe rapid aryl synthesis aldehydes of 2-aryl-benzothia/(oxa)zoles in the presence of Acacia theconventionalby the condensation condensation method, of 2-aminothiophenol of the 2-aminothiophenol microwave irradiation and diverse and diversete arylchnique aldehydes aryl has aldehydes shown in the a presence shorterin the presence reaction of Acacia timeof concinna Acacia with concinnaby the condensation as a biocatalyst of 2-aminothiophenol under microwave and irradiation diverse aryl (Scheme aldehydes 10). inIn thecomparison presence ofwith Acacia the ashigherconcinna a biocatalyst yields as aof biocatalystthe under anticipated microwave under products. microwave irradiation Furthermor (Schemeirradiatione, the10 ). reaction(Scheme In comparison course10). In is withquitecomparison theeco-friendly conventional with duethe conventionalconcinna as method,a biocatalyst the microwave under microwave irradiation irradiation technique (Schemehas shown 10). a shorterIn comparison reaction timewith with the method,toconventional the fact the that microwave method, no solvent the irradiation ismicrowave used in technique this irradiation procedure. has shownte chnique a shorter has shown reaction a shorter time with reaction higher time yields with of higherconventional yields method,of the anticipated the microwave products. irradiation Furthermor techniquee, the reactionhas shown course a shorter is quite reaction eco-friendly time with due thehigher anticipated yields of products. the anticipated Furthermore, products. the Furthermor reaction coursee, the is reaction quite eco-friendly course is quite due toeco-friendly the fact that due no tohigher the fact yields that of no the solvent anticipated is used products. in this procedure. Furthermor e, the reaction course is quite eco-friendly due solventto the fact is usedthat no in thissolvent procedure. is used in this procedure. to the fact that no solvent is used in this procedure.

Scheme 10. Condensation of 2-aminothiophenol and aryl aldehydes under microwave irradiation.

Scheme 10. Condensation of 2-aminothiophenol and aryl aldehydes under microwave irradiation. 2.1.2. CondensationScheme 10. Condensation of 2-Aminothiophenol of 2-aminothiophenol with Ketones and aryl aldehydes under microwave irradiation. Scheme 10. Condensation of 2-aminothiophenol and aryl aldehydes under microwave irradiation. 2.1.2.The Condensation condensation of 2-Am 2-Aminothiophenolof ortho-aminobenzenethiolinothiophenol with Ketones and its derivatives with representative ketones 2.1.2. Condensation of 2-Aminothiophenol with Ketones 2.1.2.to yield Condensation 2,2-disubstituted of 2-Am benzothiazolinesinothiophenol with has Ketones been investigated by Elderfield and colleagues The condensation of ortho-aminobenzenethiol an andd its derivatives with representative ketones (SchemeThe condensation11) [52]. Notably, of ortho-aminobenzenethiol pyrolysis of benzothiazoline and itscould derivatives yield a with2-substituted representative benzothiazole ketones to yieldThe 2,2-disubstitutedcondensation2,2-disubstituted of ortho-aminobenzenethiol benzothiazolines has been and investigatedits derivatives by with ElderﬁeldElderfield representative and colleaguescolleagues ketones andto yield eliminate 2,2-disubstituted hydrocarbons benzothiazolines under reflux conditions. has been investigated by Elderfield and colleagues (Schemeto yield 1111)2,2-disubstituted)[ 52[52].]. Notably, Notably, pyrolysis benzothiazolinespyrolysis of of benzothiazoline benzothi has azolinebeen couldinvestigated could yield yield a 2-substituted bya 2-substituted Elderfield benzothiazole and benzothiazole colleagues and (Scheme 11) [52]. Notably, pyrolysis of benzothiazoline could yield a 2-substituted benzothiazole eliminateand(Scheme eliminate 11) hydrocarbons [52]. hydrocarbons Notably, under pyrolysis under reﬂux reflux conditions.of benzothi conditions.azoline could yield a 2-substituted benzothiazole and eliminate hydrocarbons under reflux conditions. and eliminate hydrocarbons under reflux conditions.

Scheme 11. Condensation of o-aminobenzenethiol with ketones.

Scheme 11. Condensation of o-aminobenzenethiol with ketones. Deng et al. Scheme[53] have 11. Condensation reported ofan o-aminobenzenethiol efficient 2-arylbenzothiazole with ketones. formation from Scheme 11. Condensation of o-aminobenzenethiol with ketones. 2-aminobenzenethiolsDeng et al. [53 and] havearyl ketones reported using an mo elecularﬃcient oxygen 2-arylbenzothiazole as an oxidant under formation metal- from and Deng et al. [53] have reported an efficient 2-arylbenzothiazole formation from 2-aminobenzenethiolsI2-freeDeng conditions et al. (Scheme[53] and have aryl12). ketonesForreported a comparativ using an molecular efficiente study, oxygen 2-arylbenzothiazolethe authors as an oxidant have employed underformation metal- various from and 2-aminobenzenethiolsDeng et al. [53] and havearyl ketonesreported using an mo efficientlecular oxygen2-arylbenzothiazole as an oxidant underformation metal- from and I2-aminobenzenethiolssolvents,2-free conditions such as toluene, (Scheme and chlorobenzene, aryl12). ketones For a comparativeusing N,N-dimethylformamide molecular study, oxygen the authorsas (DMF), an oxidant have DMSO, employedunder toluene/DMSO, metal- various and I2-aminobenzenethiols2-free conditions (Scheme and aryl12). ketonesFor a comparativusing moleculare study, oxygen the authorsas an oxidant have employedunder metal- various and solvents,chlorobenzene/DMSO,I2-free conditions such as toluene, (Scheme and chlorobenzene, so12). on. For However, a comparativN,N -dimethylformamidechloroe benzene/DMSOstudy, the authors (DMF), has beenhave DMSO, provenemployed toluene as the/variousDMSO, best Isolvents,2-free conditions such as toluene,(Scheme chlorobenzene, 12). For a comparativ N,N-dimethylformamidee study, the authors (DMF), have DMSO, employed toluene/DMSO, various chlorobenzenesolventsolvents, systemsuch/ DMSO,as intoluene, terms and chlorobenzene,so of on. yield. However, Furthermor N chlorobenzene,N-dimethylformamidee, this/DMSO method has (DMF), beenrealized proven DMSO, the as toluene/DMSO,preparation the best solvent of chlorobenzene/DMSO,solvents, such as toluene, and chlorobenzene, so on. However, N,N -dimethylformamidechlorobenzene/DMSO (DMF), has been DMSO, proven toluene/DMSO, as the best systemchlorobenzene/DMSO,benzothiazoles in terms ofunder yield. metal-freeand Furthermore, so on. andHowever, thisiodine-free method chloro realizedconditionsbenzene/DMSO the preparationand hadhas excellentbeen of benzothiazoles proven universality as the under best of chlorobenzene/DMSO,solvent system in terms and soof on.yield. However, Furthermor chloroe, benzene/DMSOthis method realizedhas been theproven preparation as the best of metal-freesolventfunctional system andgroups, iodine-free in whichterms conditionsofshowed yield. that andFurthermor hadmethyl excellent,e, methoxy,this universality method fluorine, realized of functionalchlorine, the preparation groups,bromine, which and of benzothiazolessolvent system underin terms metal-free of yield. and Furthermoriodine-free e,conditions this method and hadrealized excellent the preparationuniversality of showednitro-substitutedbenzothiazoles that methyl, under raw methoxy, materialsmetal-free ﬂuorine, can and be chlorine,successfulliodine-free bromine,y conditionsconverted and nitro-substituted intoand a hadproduct excellent of raw the materials universalitycorresponding can beof benzothiazolesfunctional groups, under which metal-free showed and that iodine-free methyl , conditionsmethoxy, andfluorine, had excellentchlorine, universalitybromine, and of successfullysubstituent.functional groups, converted which into ashowed product ofthat the correspondingmethyl, methoxy, substituent. fluorine, chlorine, bromine, and nitro-substitutedfunctional groups, raw which materials showed can be that successfull methyly, convertedmethoxy, intofluorine, a product chlorine, of the correspondingbromine, and nitro-substituted raw materials can be successfully converted into a product of the corresponding substituent.nitro-substituted raw materials can be successfully converted into a product of the corresponding substituent. substituent.

Scheme 12. Scheme 12. Condensation of 2-aminobenze 2-aminobenzenethiolsnethiols and aryl ketones.

The eﬀectiveScheme condensation 12. Condensation of 2-aminobenzenethiol of 2-aminobenzenethiols with β and-diketone aryl ketones. was carried out using Scheme 12. Condensation of 2-aminobenzenethiols and aryl ketones. Scheme 12. Condensation of 2-aminobenzenethiols and aryl ketones. toluenesulfonic acid as the catalyst under oxidant-, metal-, and radiation-free conditions by Bao and co-authors [54] to oﬀer a series of 2-substituted benzenes in excellent yields (Scheme 13). To screen Molecules 2020, 25, x 6 of 17

Molecules 2020, 25, x 6 of 17 MoleculesThe 2020 effective, 25, x condensation of 2-aminobenzenethiol with β-diketone was carried out using6 of 17 toluenesulfonic acid as the catalyst under oxidant-, metal-, and radiation-free conditions by Bao and The effective condensation of 2-aminobenzenethiol with β-diketone was carried out using co-authorsThe effective [54] to offercondensation a series of of 2-substituted 2-aminobenzenethiol benzenes inwith excellent β-diketone yields was(Scheme carried 13). outTo screenusing toluenesulfonic acid as the catalyst under oxidant-, metal-, and radiation-free conditions by Bao and toluenesulfonicout the optimal acidcatalytic as the system, catalyst the under authors oxidant-, tried differentmetal-, and acids, radiation-free such as benzoic conditions acid (PhCOOH),by Bao and Moleculesco-authors2020 ,[54]25, 1675to offer a series of 2-substituted benzenes in excellent yields (Scheme 13). To screen6 of 16 co-authorstrifluoroacetic [54] acid to offer (CF 3aCOOH), series of and 2-substituted acetic acid be(CHnzenes3COOH). in excellent However, yields TsOH·H (Scheme2O was 13). chosen To screen as a out the optimal catalytic system, the authors tried different acids, such as benzoic acid (PhCOOH), outcatalyst the optimalfor solvent catalytic screening system, inthe terms authors of triedyield. different The mechanism acids, such showedas benzoic that acid the (PhCOOH), Brønsted trifluoroacetic acid (CF3COOH), and acetic acid (CH3COOH). However, TsOH·H2O was chosen as a trifluoroaceticoutacid-catalyzed the optimal acidcondensation catalytic (CF3COOH), system, reaction and the acetic authorsof 2-amino acid tried (CH thiophenol di3COOH).fferent with acids, However, 2,4-pentan such asTsOH·H benzoicedione2O would acidwas (PhCOOH),chosen take place as a trifluoroaceticcatalyst for solvent acid (CF screeningCOOH), andin terms acetic acidof yi (CHeld. COOH).The mechanism However, showed TsOH H thatO was the chosen Brønsted as a catalystto generate for a solventketamine screening3 intermed iniate terms in the ofpresence yield. 3ofThe TsOH·H mechanism2O. The showedintramolecular 2that the nucleophilic Brønsted acid-catalyzed condensation reaction of 2-amino thiophenol with 2,4-pentanedione· would take place acid-catalyzedcatalystaddition for and solvent the condensation C screening−C bond inreactioncleavage terms ofof reaction yield. 2-amino The would th mechanismiophenol finally with showed occur 2,4-pentan to that generate theedione Brønsted the would target acid-catalyzed take product. place to generate a ketamine intermediate in the presence of TsOH·H2O. The intramolecular nucleophilic tocondensationThis generate method a ketamine reactionhas a host ofintermed 2-aminoof advantages,iate thiophenol in the including presence with 2,4-pentanedione mildof TsOH·H reaction2O. conditions,The would intramolecular take simple place experimental tonucleophilic generate a additionketamine and intermediate the C−C inbond the presencecleavage ofreaction TsOH H wouldO. The finally intramolecular occur to generate nucleophilic the additiontarget product. and the steps, simple and readily available raw materials,· 2 good substrate universality, and so on, and it has a ThisC C method bond cleavage has a host reaction of advantages, would finally including occur to mild generate reaction the target conditions, product. simple This methodexperimental has a good− application prospect. steps,host of simple advantages, and readily including available mild raw reaction materials, conditions, good simplesubstrate experimental universality, steps, and simpleso on, and and it readily has a goodavailable application raw materials, prospect. good substrate universality, and so on, and it has a good application prospect.

Scheme 13. Condensation of 2-aminobenzenethiol with β-diketone.

Scheme 13. Condensation of 2-aminobenzenethiol with β-diketone. An efficient oneScheme pot strategy 13. Condensation has been developedof 2-aminobenzenethiol for the synthesis with β -diketone.of-diketone. 2-acylbenzothiazoles from aryl methyl ketones and 2-aminobenzenethiol under metal-free conditions by Loukrakpam and An efficient eﬃcient one one pot pot strategy strategy has has been been developed developed for forthe synthesis the synthesis of 2-acylbenzothiazoles of 2-acylbenzothiazoles from co-workersAn efficient (Scheme one pot14) strategy[55]. The has mechanism been developed shows forthat the the synthesis aromatic of ketones 2-acylbenzothiazoles are initially treated from fromaryl methyl aryl methyl ketones ketones and 2-aminobenzenethiol and 2-aminobenzenethiol under under metal-free metal-free conditions conditions by Loukrakpam by Loukrakpam and arylwith methylTsNBr 2ketones in DMSO and 2-aminobenzenethiolat 65°C for 3 h, and under the metal-freecrude reaction conditions mixture by Loukrakpam is treated withand andco-workers co-workers (Scheme (Scheme 14) [55]. 14)[ The55]. mechanism The mechanism shows showsthat the that aromatic the aromatic ketones ketones are initially are initiallytreated co-workers2-aminobenzenethiol (Scheme 14)via [55].condensation, The mechanism Michael shows addition, that andthe aromaticoxidative ketones dehydrogenation are initially sequence treated treatedwith TsNBr with2 TsNBrin DMSO2 in DMSO at 65°C at 65for◦C 3 for h, 3and h, and the thecrude crude reaction reaction mixture mixture is is treated treated with withto afford TsNBr the 2desired in DMSO products. at 65°C for 3 h, and the crude reaction mixture is treated with 2-aminobenzenethiol viavia condensation,condensation, Michael Michael addition, addition, and and oxidative oxidative dehydrogenation dehydrogenation sequence sequence to toaﬀ affordord the the desired desired products. products.

Scheme 14. Condensation of aryl methyl ketones and 2-aminobenzenethiol.

Scheme 14. Condensation of aryl methyl ketones and 2-aminobenzenethiol. 2.1.3. CondensationScheme of 2-Aminobenzenethiol 14. Condensation of aryl with methyl Acids ketones and 2-aminobenzenethiol. 2.1.3. Condensation of 2-Aminobenzenethiol with Acids 2.1.3.Gupta Condensation and co-workers of 2-Aminobenzenethiol [56] have reported with thatAcids molecular iodine was utilized in a one-pot, solid-phase,Gupta andsolvent-free co-workers reaction [56] between have reported 2-aminothiophenol that molecular and iodine benzoic was acid utilized derivatives in a to one-pot, obtain Gupta and co-workers [56] have reported that molecular iodine was utilized in a one-pot, solid-phase,an excellentGupta and solvent-free yield co-workers of reactionbenzothiazole [56] betweenhave reportedderivatives 2-aminothiophenol that formolecular 10 min and iodine benzoic(Scheme was acid utilized15). derivatives Compared in a toone-pot, obtainwith solid-phase, solvent-free reaction between 2-aminothiophenol and benzoic acid derivatives to obtain solid-phase,anpolyphosphoric excellent yieldsolvent-free acid of benzothiazole and reaction [pmim]-Br between derivatives catalyzed 2-aminothiophenol for 10 microwave min (Scheme andsynthesis, 15 benzoic). Compared theacid newderivatives with polyphosphoricmethod to obtainhas a an excellent yield of benzothiazole derivatives for 10 min (Scheme 15). Compared with anacidsignificantly excellent and [pmim]-Br reducedyield catalyzedof cost benzothiazole due microwave to the factderivatives synthesis, that no additional thefor new 10 methodmin chemicals (Scheme has aand signiﬁcantly 15).solvents Compared reducedare essential with cost polyphosphoric acid and [pmim]-Br catalyzed microwave synthesis, the new method has a polyphosphoricdueduring to thethe facttransformation. thatacid no and additional [pmim]-BrThis methodology chemicals catalyzed and has solventsmicrowavethe advantages are synthesis, essential of being duringthe highly new the economical, transformation.method has less a significantly reduced cost due to the fact that no additional chemicals and solvents are essential significantlyThistime methodologyconsuming, reduced and has solvent-free. thecost advantages due to the of fact being that highly no additional economical, chemicals less timeconsuming, and solvents and are solvent-free. essential during the transformation. This methodology has the advantages of being highly economical, less time consuming, and solvent-free.

Scheme 15. Condensation of 2-aminothiopheno 2-aminothiophenoll and benzoic acid derivatives.

Scheme 15. Condensation of 2-aminothiophenol and benzoic acid derivatives. Reuf et al.Scheme [[57]57] havehave 15. Condensation reportedreported thatthat of 2-aminothiopheno thethe 2-substituted2-substitutedl and benzothiazoles benzoic acid derivatives. were prepared by the condensation reactionreaction of ortho-aminothiophenolof ortho-aminothiophe withnol variouswith various fatty acids fatty under acids microwave under microwave irradiation for 3–4Reuf min et (Scheme al. [57] 16 have). The reported reaction that was completedthe 2-substituted with a high benzothiazoles yield of the productionswere prepared using by P theS 4 10 condensationas a catalyst. Thisreaction protocol of isortho-aminothiophe eﬃcient, rapid, andnol solvent-free. with various fatty acids under microwave

Molecules 2020, 25, x 7 of 17 Molecules 2020, 25, x 7 of 17 Molecules 2020, 25, x 7 of 17 irradiation for 3–4 min (Scheme 16). The reaction was completed with a high yield of the irradiation for 3–4 min (Scheme 16). The reaction was completed with a high yield of the irradiationproductions for using 3–4 P 4Smin10 as (Schemea catalyst. 16). This The protocol reaction is efficient, was completed rapid, and withsolvent-free. a high yield of the productionsMolecules 2020, 25using, 1675 P4S10 as a catalyst. This protocol is efficient, rapid, and solvent-free. 7 of 16 productions using P4S10 as a catalyst. This protocol is efficient, rapid, and solvent-free.

Scheme 16. Condensation of ortho-aminothiophenol with fatty acids. Scheme 16. Condensation of ortho-aminothiophenol with fatty acids. Scheme 16. Condensation of ortho-aminot ortho-aminothiophenolhiophenol with fatty acids. Sharghi et al. [58] have investigated a high-yielding method for the synthesis of a series of Sharghi et al. [[58]58] have investigated a high-yielding method for the synthesis of a series of 2-substitutedSharghi etbenzothiazole al. [58] have compou investigatednds by a the high-yielding condensation method of 2-aminobenzenethiol for the synthesis withof a differentseries of 2-substituted benzothiazole compou compoundsnds by the condensation of 2-aminobenzenethiol with different diﬀerent 2-substitutedkinds of aliphatic benzothiazole or aromatic compou carboxylicnds by acid thes condensation (Scheme 17). of The 2-aminobenzenethiol novel heterogeneous with mixture different of kinds of aliphatic or aromatic carboxylic acidsacids (Scheme(Scheme 1717).). The novel heterogeneous mixture of kindsmethanesulfonic of aliphatic acidor aromatic and silica carboxylic gel was acid developeds (Scheme to17). be The an novel expeditious heterogeneous medium mixture for the of methanesulfonic acidacid and and silica silica gel wasgel developedwas developed to be an to expeditious be an expeditious medium for medium the condensation for the methanesulfoniccondensation reaction acid ofand aromat silicaic geland wasaliphatic developed carboxylic to beacids an with expeditious 2-aminothiophenol medium forfor the condensationreaction of aromatic reaction and of aromat aliphaticic and carboxylic aliphatic acids carboxylic with 2-aminothiophenol acids with 2-aminothiophenol for the synthesis for the of condensationsynthesis of 2-substituted reaction of aromatbenzothiazoles.ic and aliphatic In additi carboxylicon, silica could acids bewith reused 2-aminothiophenol multiple times without for the synthesis2-substituted of 2-substituted benzothiazoles. benzothiazoles. In addition, In silica additi couldon, silica be reused could be multiple reused times multiple without times reducing without synthesisreducing ofthe 2-substituted yield. Simplicity, benzothiazoles. use of widely In additi availableon, silica and could diverse be reused carboxylic multiple acids, times and without easy reducingthe yield. the Simplicity, yield. Simplicity, use of widely use available of widely and available diverse carboxylicand diverse acids, carboxylic and easy acids, handling and ofeasy the reducinghandling ofthe the yield. reaction Simplicity, conditions use are of among widely the available benefits ofand this diverse method. carboxylic acids, and easy handlingreaction conditions of the reaction are among conditions the beneﬁts are among of this the method. benefits of this method. handling of the reaction conditions are among the benefits of this method.

Scheme 17. Condensation of 2-aminobenzenethiol with aliphatic or aromatic carboxylic acids. Scheme 17. CondensationCondensation of 2-aminobenzenethiol with aliphatic or aromatic carboxylic acids. Scheme 17. Condensation of 2-aminobenzenethiol with aliphatic or aromatic carboxylic acids. Coelho and co-workers [59] [59] have developed a simple and eefficientfficient general methodology for Coelho and co-workers [59] have developed a simple and efficient general methodology for benzothiazolesCoelho and preparation co-workers from [59] thehave condensation developed a of simple 2-aminothiophenol and efficient disulfidesdisulfidesgeneral methodology with carboxylic for benzothiazoles preparation from the condensation of 2-aminothiophenol disulfides with carboxylic acidsbenzothiazoles promoted preparation by tributylphosphinetributylphosphine from the condensation at room temperaturetemperature of 2-aminothiophenol (Scheme(Scheme 1818).). disulfides The universality with carboxylic of this acids promoted by tributylphosphine at room temperature (Scheme 18). The universality of this methodologyacids promoted waswas by investigated investigatedtributylphosphine using using 2-aminothiophenol 2-aminothiopat room temperaturehenol disulfides disulfides (Scheme and and various18). variousThe carboxylic universality carboxylic acids of acids withthis methodology was investigated using 2-aminothiophenol disulfides and various carboxylic acids donormethodologywith donor/withdrawing/withdrawing was investigated substituents, substituents, using which 2-aminothiopwhich resulted resulted inhenol the in the desired disulfides desired benzothiazoles benzothiazolesand various with carboxylic with moderate moderate acids to with donor/withdrawing substituents, which resulted in the desired benzothiazoles with moderate excellentwithto excellent donor/withdrawing yields. yields. The The advantages advantages substituents, of of this this which solution solution resulted include include in mild the mild reactiondesired reaction benzothiazoles conditions conditions and and with the the addition moderate addition of to excellent yields. The advantages of this solution include mild reaction conditions and the addition non-toxictoof excellentnon-toxic reagents. yields. reagents. The advantages of this solution include mild reaction conditions and the addition of non-toxic reagents. of non-toxic reagents.

Scheme 18. Condensation of 2-aminothiophenol disulfidesdisulfides with carboxylic acids. Scheme 18. Condensation of 2-aminothiophenol disulfides with carboxylic acids. 2.1.4. CondensationScheme of 18. 2-Aminobenzenethiol Condensation of 2-aminothiophenol with Acyl Chloride disulfides with carboxylic acids. 2.1.4. Condensation of 2-Aminobenzenethiol with Acyl Chloride 2.1.4.Nadaf Condensation et al. [60 ]of have 2-Aminobenzenethiol suggested an efficient with catalyst Acyl Chloride system, 1-butylimidazole tetrafluoroborate 2.1.4.Nadaf Condensation et al. [60] of have 2-Aminobenzenethiol suggested an efficient with catalyst Acyl Chloride system, 1-butylimidazole tetrafluoroborate ionicNadaf liquid et and al. [60] 1,3-dibutylimidazole have suggested an tetrafluoroborate efficient catalyst ionicsystem, liquid 1-butylimidazole for the synthesis tetrafluoroborate of 2-aromatic ionicNadaf liquid et and al. [60]1,3-dibutylimidazole have suggested an tetrafluoroborate efficient catalyst ionic system, liquid 1-butylimidazole for the synthesis tetrafluoroborate of 2-aromatic ionicsubstituted liquid benzothiazolesand 1,3-dibutylimidazole through the tetrafluoroborate condensationof ionic 2-aminobenzenethiol liquid for the synthesis with aromaticof 2-aromatic acid ionicsubstituted liquid benzothiazolesand 1,3-dibutylimidazole through the tetrafluoroborate condensation of ionic 2-aminobenzenethiol liquid for the synthesis with aromaticof 2-aromatic acid substitutedchloride compounds benzothiazoles at room through temperature the (Schemecondensation 19). In of this 2-aminobenzenethiol study, several new ILs with were aromatic synthesized, acid substitutedchloride compounds benzothiazoles at room through temperature the condensation (Scheme of19). 2-aminobenzenethiol In this study, several with newaromatic ILs wereacid chloridecharacterized, compounds and screened at room for these temperature reactions. (Scheme The mild reaction19). In conditions,this study, absenceseveral ofnew a catalyst, ILs were and chloridesynthesized, compounds characterized, at room and temperaturescreened for these(Scheme reactions. 19). In The this mild study, reaction several conditions, new ILs absence were synthesized,recyclabilityMolecules 2020, 25 ofcharacterized,, thex non-volatile and ILs screened make an for environment-friendly these reactions. The methodology mild reaction amenable conditions, for scaleabsence8 of up. 17 synthesized,of a catalyst, characterized,and recyclability and of screened the non-volatile for these ILsreactions. make an The environment-friendly mild reaction conditions, methodology absence of a catalyst, and recyclability of the non-volatile ILs make an environment-friendly methodology ofamenable a catalyst, for andscale recyclability up. of the non-volatile ILs make an environment-friendly methodology amenable for scale up. amenable for scale up.

Scheme 19. Condensation of 2-aminobenzenethiol wi withth aromatic acid chloride compounds.

Wu and colleagues [61] have reported that novel dibenzothiazole derivatives were synthesized. In this work, zinc salt of 4-amino-3-mercaptobenzoic acid was suspended in pyridine with para-nitro benzoyl chloride at 80 °C for an hour and converted into 2-(4′-nitrophenyl)-benzothiazole-6-carbonyl chloride by treatment with thionyl chloride (SOCl2) (Scheme 20). Meanwhile, di-benzthiazole-containing compounds were obtained by adding 5-substituted aminothiophenols and heating to reflux for 3 h.

Scheme 20. Reaction of 4-amino-3-mercaptobenzoic acid with para-nitro benzoyl chloride.

Racane et al. [62] have reported that the efficient synthesis of nitro-amidino benzothiazoles by a condensation reaction of nitro-substituted 2-aminobenzothiole with commercially available 4-nitrobenzoylchloride under reflux conditions in acetic acid (AcOH) for 4 h (Scheme 21). The target compounds were used as starting compounds for the preparation of targeted amidino substituted 2-phenylbenzothiazole by the Pinner reaction.

Scheme 21. Condensation of nitro-substituted 2-aminobenzothiole with 4-nitrobenzoylchloride.

An efficient protocol was developed by Kumar and co-workers [63] for the preparation of a library of benzothiazole derivatives from reactions of acyl chlorides with ortho-aminothiophenol in the presence of a catalytic amount of silica-supported sodium hydrogen sulfate (NaHSO4-SiO2) under solvent-free conditions (Scheme 22). The catalyst NaHSO4-SiO2 can easily be prepared from the readily available NaHSO4 and silica gel (230–400 mesh), and these are inexpensive and non-toxic. Furthermore, as the reaction is heterogeneous in nature, the catalyst could be easily removed by simple filtration. A simple workup procedure, high yield, easy availability, reusability, and the use of eco-friendly catalysts are some of the advantages of the present suggestion.

Molecules 2020, 25, x 8 of 17 Molecules 2020, 25, x 8 of 17

Molecules 2020, 25, 1675 8 of 16 SchemeScheme 19.19. CondensationCondensation ofof 2-aminobenzenethiol2-aminobenzenethiol wiwithth aromaticaromatic acidacid chloridechloride compounds.compounds.

Wu and colleagues [61] have reported that novel dibenzothiazole derivatives were synthesized. Wu and colleagues [61] [61] have reported that novel dibenzothiazole dibenzothiazole derivatives derivatives were were synthesized. synthesized. In this work, zinc salt of 4-amino-3-mercaptobenzoic acid was suspended in pyridine with In thisthis work, work, zinc zinc salt salt of 4-amino-3-mercaptobenzoic of 4-amino-3-mercaptobenzoic acid wasacid suspended was suspended in pyridine in withpyridine para-nitro with para-nitro benzoyl chloride at 80 °C for an hour and converted into para-nitrobenzoyl chloride benzoyl at 80 ◦Cchloride for an hour at and converted80 °C intofor 2-(4 0an-nitrophenyl)-benzothiazole- hour and converted 6-carbonyl into 2-(4′-nitrophenyl)-benzothiazole-6-carbonyl chloride by treatment with thionyl chloride (SOCl2) 2-(4chloride′-nitrophenyl)-benzothiazole-6-carbonyl by treatment with thionyl chloride chloride (SOCl2 )by (Scheme treatment 20). with Meanwhile, thionyl chloride di-benzthiazole- (SOCl2) (Scheme 20). Meanwhile, di-benzthiazole-containing compounds were obtained by adding (Schemecontaining 20). compounds Meanwhile, were obtaineddi-benzthiazole-contai by adding 5-substitutedning compounds aminothiophenols were obtained and heating by toadding reﬂux 5-substituted aminothiophenols and heating to reflux for 3 h. 5-substitutedfor 3 h. aminothiophenols and heating to reflux for 3 h.

SchemeScheme 20. 20. ReactionReaction ofof 4-amino-3-mercaptobenzoic4-amino-3-mercaptobenzoic ac acidacidid with with para-nitro para-nitro benzoyl benzoyl chloride.chloride.

RacaneRacane etet al.al. al. [62][62] [62 ]havehave have reportedreported reported thatthat that thethe the efficieffici eﬃententcient synthesissynthesis synthesis ofof nitro-amidnitro-amid of nitro-amidinoinoino benzothiazolesbenzothiazoles benzothiazoles byby aa condensationbycondensation a condensation reactionreaction reaction ofof nitro-substituted ofnitro-substituted nitro-substituted 2-2-aminobenzothioleaminobenzothiole 2-aminobenzothiole withwith with commerciallycommercially commercially availableavailable 4-nitrobenzoylchloride4-nitrobenzoylchloride under under reflux reﬂuxreflux conditionsconditions inin aceticacetic acidacid (AcOH)(AcOH) forfor 44 hh (Scheme(Scheme 2121).21).). TheThe target target compoundscompounds were were used used as as startingstarting compoundscompounds for for thethe preparationpreparation ofof targetedtargeted amidinoamidino substitutedsubstituted 2-phenylbenzothiazole2-phenylbenzothiazole by by thethe PinnerPinner reaction.reaction.

Scheme 21. Condensation of nitro-substituted 2-aminobenzothiole with 4-nitrobenzoylchloride. SchemeScheme 21.21. CondensationCondensation ofof nitro-substitutednitro-substituted 2-aminob2-aminobenzothioleenzothiole withwith 4-nitrobenzoylchloride.4-nitrobenzoylchloride.

An eefficientﬃcient protocolprotocol was developeddeveloped by Kumar and co-workers [[63]63] forfor thethe preparationpreparation of aa libraryAn of efficient benzothiazole protocol derivatives was developed from reactions by Kumar of acyland chloridesco-workers with [63] ortho-aminothiophenol for the preparation of ina librarylibrary ofof benzothiazolebenzothiazole derivativesderivatives fromfrom reactionsreactions ofof acylacyl chlorideschlorides withwith ortho-aminothiophenolortho-aminothiophenol inin the presence of a catalytic amount of silica-supported sodium hydrogen sulfate (NaHSO4-SiO2) under the presence of a catalytic amount of silica-supported sodium hydrogen sulfate (NaHSO4-SiO2) thesolvent-free presence conditions of a catalytic (Scheme amount 22). The of catalystsilica-supported NaHSO -SiO sodiumcan easilyhydrogen be prepared sulfate from(NaHSO the readily4-SiO2) under solvent-free conditions (Scheme 22). The catalyst4 NaHSO2 4-SiO2 can easily be prepared from underavailable solvent-free NaHSO and conditions silica gel (S (230–400cheme 22). mesh), The and catalyst these areNaHSO inexpensive4-SiO2 can and easily non-toxic. be prepared Furthermore, from the readily available4 NaHSO4 and silica gel (230–400 mesh), and these are inexpensive and non-toxic. the readily available NaHSO4 and silica gel (230–400 mesh), and these are inexpensive and non-toxic. asFurthermore, the reaction as is the heterogeneous reaction is heterogeneous in nature, the catalyst in nature, could the be catalyst easily removedcould be byeasily simple removed ﬁltration. by AFurthermore, simple workup as the procedure, reaction is high heterogeneous yield, easy availability,in nature, the reusability, catalyst could and thebe useeasily of removed eco-friendly by simplesimple filtration.filtration. AA simplesimple workupworkup procedure,procedure, highhigh yield,yield, easyeasy availability,availability, reusability,reusability, andand thethe useuse catalystsMolecules 2020 are, 25 some, x of the advantages of the present suggestion. 9 of 17 ofof eco-friendlyeco-friendly catalystscatalysts areare somesome ofof thethe advantagesadvantages ofof thethe presentpresent suggestion.suggestion.

Scheme 22.22. Condensation of acyl chlorideschlorides with ortho-aminothiophenol.

Dar and co-workers [64] have investigated a synthesis of benzothiazoles using a one-pot three-component reaction between thiols, oxalyl chloride, and 2-aminothiophenol in the presence of n-tetrabutylammonium iodide (TBAI) at 60 °C (Scheme 23). The present protocol favored the formation of the desired products via simultaneous formation of C−N and C−S bonds in good yields with a wide range of substrates. The advantages of this method include mild reaction conditions and high efficiency.

Scheme 23. Reaction of thiols, oxalyl chloride, and 2-aminothiophenol.

Luo and co-authors [65] found that 2-chloromethyl-benzothiazole could be obtained from the condensation of 2-aminothiophenols with chloroacetyl chloride in acetic acid under microwave irradiation for 10 min (Scheme 24). Compared with the traditional methods, the microwave-assisted procedures were efficient and environmentally friendly, with less time and high yield.

Scheme 24. Condensation of 2-aminothiophenols with chloroacetyl chloride.

2.2. By Cyclization

2.2.1. Cyclization of Various Substituted Thioamides Bose and co-workers [66] have developed an environmentally beneficial, efficient, and rapid procedure for the synthesis of benzothiazoles via the cyclization of sulfamide substrates in the existence of Dess-Martin periodinane as the catalyst in dichloromethane as the reaction solvent at room temperature for 15 min (Scheme 25). The mechanism shows that the reaction proceeds via a thiyl radical in high yields to give the novel compound oxybis benzothiazole and is also amenable to generating combinatorial libraries of heterocyclic compounds by solid-phase synthesis. This method has the advantages of short reaction cycle, simple operation, good yield, mild conditions, etc.

Scheme 25. Cyclization of sulfamide substrates.

Molecules 2020, 25, x 9 of 17 Molecules 2020, 25, x 9 of 17

Molecules 2020, 25, 1675Scheme 22. Condensation of acyl chlorides with ortho-aminothiophenol. 9 of 16 Scheme 22. Condensation of acyl chlorides with ortho-aminothiophenol. Dar and co-workers [64] have investigated a synthesis of benzothiazoles using a one-pot Dar and co-workers [64] have investigated a synthesis of benzothiazoles using a one-pot three-componentDar and co-workers reaction between [[64]64] havehave thiols, investigatedinvestigated oxalyl ch loride, aa synthesissynthesis and 2-aminothiophenol ofof benzothiazolesbenzothiazoles in using the presence a one-potone-pot of three-component reaction between thiols, oxalyl chloride, and 2-aminothiophenol in the presence of n-tetrabutylammoniumthree-component reaction reaction iodide between between (TBAI) thiols, thiols, at oxalyl oxalyl60 °C ch chloride,(Schemeloride, and and23). 2-aminothiophenol 2-aminothiophenolThe present protocol in inthe thefavored presence presence the of n-tetrabutylammonium iodide (TBAI) at 60 °C (Scheme 23). The present protocol favored the formationofn-tetrabutylammonium n-tetrabutylammonium of the desired productsiodide iodide (TBAI) via (TBAI) simultaneous at at60 60 °C◦C (Scheme (Schemeformation 23).23 of). CThe The−N presentand present C−S protocol protocolbonds in favored good yields thethe formation of the desired products via simultaneous formation of C−N and C−S bonds in good yields withformation a wide ofof range thethe desireddesired of substrates. productsproducts The viavia advantages simultaneoussimultaneous of this formationformation method ofof include CC−NN andand mild CC −reactionS bonds conditions in good yields and with a wide range of substrates. The advantages of this method include− mild− reaction conditions and withhighwith aefficiency.a wide range of substrates. The advantages of this method include mild reaction conditions and high eefficiency.ﬃciency.

Scheme 23. Reaction of thiols, oxalyl chloride, and 2-aminothiophenol. Scheme 23. Reaction of thiols, oxalyl ch chloride,loride, and 2-aminothiophenol. Luo and co-authors [65] found that 2-chloromethyl-benzothiazole could be obtained from the Luo and co-authors [[65]65] found thatthat 2-chloromethyl-benzothiazole2-chloromethyl-benzothiazole could be obtained from the condensationLuo and co-authorsof 2-aminothiophenols [65] found that with 2-chloromethyl-benzothiazole chloroacetyl chloride in acetic could acid be underobtained microwave from the condensation of 2-aminothiophenols with chloroac chloroacetyletyl chloride in acetic acid under microwave irradiationcondensation for of10 min2-aminothiophenols (Scheme 24). Compared with chloroac with theetyl traditional chloride methods,in acetic theacid microwave-assisted under microwave irradiation for 10 min (Scheme 2424).). Compared with the traditional methods, the microwave-assisted proceduresirradiation forwere 10 efficientmin (Scheme and environmentally 24). Compared with friendly, the traditional with less time methods, and high the microwave-assistedyield. procedures werewere eefficientﬃcient andand environmentallyenvironmentally friendly,friendly, with with less less time time and and high high yield. yield.

Scheme 24. Condensation of 2-aminothiophenols with chloroacetyl chloride. Scheme 24. Condensation of 2-aminothiophenols with chloroacetyl chloride. Scheme 24. Condensation of 2-aminothiophenols with chloroacetyl chloride. 2.2. By By Cyclization Cyclization 2.2. By Cyclization 2.2.1. Cyclization Cyclization of of Various Various Substituted Thioamides 2.2.1. Cyclization of Various Substituted Thioamides Bose and co-workers [66] [66] have developed an environmentallyenvironmentally beneﬁcial,beneficial, efficient, eﬃcient, and rapid Bose and co-workers [66] have developed an environmentally beneficial, efficient, and rapid procedureBose and for theco-workers synthesis [66] of have benzothiazoles developed via an en thevironmentally cyclization of beneficial, sulfamide efficient, substrates and in rapid the procedure for the synthesis of benzothiazoles via the cyclization of sulfamide substrates in the existenceprocedure of for Dess-Martin the synthesis periodinane of benzothiazoles as the catalyst via the in dichloromethane cyclization of sulfamide as the reaction substrates solvent in the at existence of Dess-Martin periodinane as the catalyst in dichloromethane as the reaction solvent at roomexistence temperature of Dess-Martin for 15 minperiodinane (Scheme as 2525). the). The catalyst me mechanismchanism in dichloromethane shows that the as reaction the reaction proceeds solvent via ata room temperature for 15 min (Scheme 25). The mechanism shows that the reaction proceeds via a thiylroom radical temperature in high for yields 15 min to give (Scheme the novel 25). compound The mechanism oxybis shows benzothiazole that the reactionand is also proceeds amenable via to a thiyl radical in high yields to give the novel compound oxybis benzothiazole and is also amenable to generatingthiyl radical combinatorial in high yields libraries to give the of heterocyclic novel compound compounds oxybis by benzothiazole solid-phase synthesis.and is also This amenable method to generating combinatorial libraries of heterocyclic compounds by solid-phase synthesis. This method hasgenerating the advantages combinatorial of short libraries reaction of cycle, heterocyclic simple compounds operation, good by solid-phase yield, mildmild synthesis. conditions,conditions, This etc.etc. method has the advantages of short reaction cycle, simple operation, good yield, mild conditions, etc.

Scheme 25. Cyclization of sulfamide substrates. Scheme 25. Cyclization of sulfamide substrates. Downer and colleagues [67] have investigated a general method for the intramolecular cyclization of thiobenzamides to benzothiazoles via aryl radical cations as reactive intermediates under mild conditions (Scheme 26). In this method, the usage of phenyliodine(III) bis(triﬂuoroacetate) (PIFA) in triﬂuoroethanol or cerium ammonium nitrate (CAN) in aqueous acetonitrile was to promote cyclization within 30 min at room temperature in moderate yields. Molecules 2020, 25, x 10 of 17 Molecules 2020, 25, x 10 of 17 Downer and colleagues [67] have investigated a general method for the intramolecular Downer and colleagues [67] have investigated a general method for the intramolecular cyclization of thiobenzamides to benzothiazoles via aryl radical cations as reactive intermediates cyclizationcyclization ofof thiobenzamidesthiobenzamides toto benzothiazolesbenzothiazoles viavia arylaryl radicalradical cationscations asas reactivereactive intermediatesintermediates under mild conditions (Scheme 26). In this method, the usage of phenyliodine(III) under mild conditions (Scheme 26). In thisis method,method, thethe usageusage of phenyliodine(III) bis(trifluoroacetate) (PIFA) in trifluoroethanol or cerium ammonium nitrate (CAN) in aqueous bis(trifluoroacetate) (PIFA) in trifluoroethanoltrifluoroethanol oror ceriumcerium ammoammonium nitrate (CAN) in aqueous acetonitrileMolecules 2020 ,was25, 1675 to promote cyclization within 30 min at room temperature in moderate yields.10 of 16 acetonitrile was to promote cyclization within 30 min at room temperature in moderate yields.

Scheme 26. Cyclization of thiobenzamides at room temperature. Scheme 26. Cyclization of thiobenzamides at room temperature.

Rey and co-workers [68] [68] reported that 2-substituted benzothiazoles were efficiently eﬃciently synthesized Rey and co-workers [68] reported that 2-substituted benzothiazoles were efficiently synthesized by radicalradical cyclization cyclization of thioformanilides of thioformanilides induced byinduced chloranil by under chloranil irradiation under in 1,2-dichloroethane irradiation in by radical cyclization of thioformanilides induced by chloranil under irradiation in 1,2-dichloroethaneand toluene at 80 C and (Scheme toluene 27). at Especially, 80 °C (Scheme hydrogen 27). atom Especially, abstraction hydrogen from thiobenzamide atom abstraction by tripletfrom 1,2-dichloroethane◦ and toluene at 80 °C (Scheme 27). Especially, hydrogen atom abstraction from thiobenzamidechloranil was the by keytriplet step chloranil of themechanism. was the key step The protocolof the mechanism. was simple, The and protocol the heterocycles was simple, were and thiobenzamidethiobenzamide byby triplettriplet chloranilchloranil waswas thethe keykey stepstep ofof thethe mechanism.mechanism. TheThe protocolprotocol waswas simple,simple, andand theeasily heterocycles isolated from were the easily reaction isolated mixture. from the reaction mixture. thethe heterocyclesheterocycles werewere easilyeasily isolatedisolated fromfrom thethe reactionreaction mixture.mixture.

Scheme 27. Cyclization of thioformanilides. Scheme 27. Cyclization of thioformanilides. An efficient, eﬃcient, economical, economical, and and convenient convenient me methodthod was was developed developed for forthe thepreparation preparation of An efficient, economical, and convenient methodthod waswas developeddeveloped forfor thethe preparationpreparation ofof 2-substitutedof 2-substituted benzothiazolesbenzothiazoles from N0-substituted-from N-(2-halophenyl)thioureas,N′-substituted-N-(2-halophenyl)thioureas,O0-substituted- 2-substituted benzothiazoles from N′′-substituted--substituted-N-(2-halophenyl)thioureas,-(2-halophenyl)thioureas, ON′-(2-halophenyl)-substituted-N-(2-halophenyl) carbamothioates, carbamothioates, or N-(2-halophenyl) or N-(2-halophenyl) thioamides through thioamides a base-promoted through a O′′-substituted--substituted-N-(2-halophenyl)-(2-halophenyl) carbamothioates,carbamothioates, oror N-(2-halophenyl)-(2-halophenyl) thioamidesthioamides throughthrough aa base-promotedintramolecular C–Sintramolecular bond coupling C–S bond cyclization coupling in dioxanecyclization without in dioxane any transition without metalany transition by Feng base-promoted intramolecular C–S bond coupling cyclization in dioxane without any transition metaland colleagues by Feng and [69] colleagues (Scheme 28 [69]). A (Scheme variety of 28). functional A variety groups of functional were tolerated groups under were thesetolerated conditions under metal by Feng and colleagues [69] (Scheme 28). A varietyriety ofof functionalfunctional groupsgroups werewere toleratedtolerated underunder theseand good conditions yields wereand achieved.good yields This methodwere achieved. has some This advantages method of has transition-metal-free, some advantages mild of thesethese conditionsconditions andand goodgood yieldsyields werewere achieved.achieved. ThisThis methodmethod hashas somesome advantagesadvantages ofof transition-metal-free,reactive conditions, wide mild application reactive conditions, scope, and wide shorter application reaction scope, times. and shorter reaction times. transition-metal-free,transition-metal-free, mildmild reactivereactive conditions,conditions, widewide applicationapplication scope,scope, andand shortershorter reactionreaction times.times.

Scheme 28. Cyclization of substituted thioformanilides. Scheme 28. Cyclization of substituted thioformanilides. Scheme 28. Cyclization of substituted thioformanilides. Cheng and co-authors [70] have developed an aerobic visible-light photoredox synthesis of Cheng and co-authors [70] have developed an aerobic visible-light photoredox synthesis of 2-substitutedCheng and benzothiazoles co-authors [70] by have radical developed cyclization an ofaerobic thioanilides visible- (Schemelight photoredox 29). The synthesis range and of 2-substituted benzothiazoles by radical cyclization of thioanilides (Scheme 29). The range and functional2-substituted group benzothiazoles compatibility by of theradical new cyclization visible-light of photocatalytic thioanilides reaction(Scheme were 29). studied,The range and and the functional group compatibility of the new visible-light photocatalytic reaction were studied, and the resultsfunctional showed group that compatibility the method of could the new tolerate visible-light many functionalphotocatalytic groups reaction and thewere reaction studied, was and very the results showed that the method could tolerate many functional groups and the reaction was very mild.results This showed method that has the the method highlights could of tolerate unique ma selectivity,ny functional high egroupsﬃciency, and and the an reaction environmentally was very mild. This method has the highlights of unique selectivity, high efficiency, and an environmentally friendlymild. This nature. method has the highlights of unique selectivity, high efficiency, and an environmentally friendlyMolecules 2020 nature., 25, x 11 of 17 friendlyfriendly nature.nature.

Scheme 29. Cyclization of thioanilides.

Folgueiras et al. [71] have reported that the catalyst-free and supporting electrolyte-free electrochemical synthesis of benzothiazoles has good to excellent yields and with high current efficiencies from arylthioamides using a flow electrochemical reactor (Scheme 30). In this method, an easy scale-up of the reaction without the need for a larger reactor largely improved the reported methods for the formation of benzothiazoles.

Scheme 30. Cyclization of arylthioamides.

Xu and colleagues [72] have developed a methodology for visible light-driven, intramolecular C−S bond formation of aromatic substrates to give benzothiazoles through the cyclization of thioamide derivatives in the presence of 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO) and obtained excellent yields (Scheme 31). Notably, this photochemical cyclization does not require an extra photoredox catalyst, transition-metal catalyst, or base.

Scheme 31. Cyclization of thioamide derivatives.

Bouchet and co-workers [73] have reported an efficient methodology for the synthesis of benzothiazoles in good to excellent yields from the cyclization of thiobenzanilides using riboflavin as a photosensitizer and potassium peroxydisulfate as a sacrificial oxidizing agent under visible light irradiation (Scheme 32). As a photocatalyst, riboflavin is an inexpensive natural reagent that shows important advances over transition-metal catalysis. In addition, the present method accepted a wide scope of functional groups and afforded the desired productions. This environmentally friendly procedure could be beneficial for pharmaceutical uses.

Scheme 32. Cyclization of thiobenzanilides under visible light.

2.2.2. Cyclization of CO2 as Raw Materials Our group has reported a new route to synthesize benzothiazoles via cyclization of 2-aminothiophenols with CO2 in the presence of diethylsilane catalyzed by

Molecules 2020, 25, x 11 of 17 Molecules 2020, 25, x 11 of 17 Molecules 2020, 25, x 11 of 17

Scheme 29. Cyclization of thioanilides. Molecules 2020, 25, 1675 Scheme 29. Cyclization of thioanilides. 11 of 16 Scheme 29. Cyclization of thioanilides. Folgueiras et al. [71] have reported that the catalyst-free and supporting electrolyte-free Folgueiras et al. [[71]71] have reported that thethe catalyst-freecatalyst-free andand supportingsupporting electrolyte-freeelectrolyte-free electrochemical synthesis of benzothiazoles has good to excellent yields and with high current electrochemical synthesis of benz benzothiazolesothiazoles has good to excellen excellentt yields and with high current efficiencies from arylthioamides using a flow electrochemical reactor (Scheme 30). In this method, eefficienciesﬃciencies from arylthioamides using a ﬂowflow electrochemical reactor (Scheme 3030).). In In this method, an easy scale-up of the reaction without the need for a larger reactor largely improved the reported an easy scale-up of the reaction without the need for a larger reactor largely improved the reported methods for the formation of benzothiazoles. methods for the formation of benzothiazoles.

Scheme 30. Cyclization of arylthioamides. Scheme 30. Cyclization of arylthioamides. Scheme 30. Cyclization of arylthioamides. XuXu andand colleaguescolleagues [[72]72] havehave developed a methodology for visible light-driven, light-driven, intramolecularintramolecular Xu and colleagues [72] have developed a methodology for visible light-driven, intramolecular CC−S bondbond formation formation of of aromatic aromatic substrates substrates to give to benzothiazolesgive benzothiazoles through through the cyclization the cyclization of thioamide of C−S bond formation of aromatic substrates to give benzothiazoles through the cyclization of derivativesthioamide inderivatives the presence in ofthe 2,2,6,6-tetramethylpiperidine presence of 2,2,6,6-tetramethylpiperidineN-oxide (TEMPO) N and-oxide obtained (TEMPO) excellent and thioamide derivatives in the presence of 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO) and yieldsobtained (Scheme excellent 31). yields Notably, (Scheme this photochemical31). Notably, th cyclizationis photochemical does not cyclization require an does extra not photoredox require an obtained excellent yields (Scheme 31). Notably, this photochemical cyclization does not require an catalyst,extra photoredox transition-metal catalyst, catalyst, transition-metal or base. catalyst, or base. extra photoredox catalyst, transition-metal catalyst, or base.

Scheme 31. Cyclization of thioamide derivatives. Scheme 31. Cyclization of thioamide derivatives. Scheme 31. Cyclization of thioamide derivatives. Bouchet and co-workers [73] have reported an efficient methodology for the synthesis of Bouchet and co-workers [73] have reported an efficient methodology for the synthesis of benzothiazolesBouchet and in goodco-workers to excellent [73] yieldshave fromreported the cyclizationan efficient of thiobenzanilidesmethodology for using the riboflavinsynthesis asof benzothiazoles in good to excellent yields from the cyclization of thiobenzanilides using riboflavin abenzothiazoles photosensitizer in andgood potassium to excellent peroxydisulfate yields from the as cyclization a sacrificial of oxidizing thiobenzanilides agent under using visible riboflavin light as a photosensitizer and potassium peroxydisulfate as a sacrificial oxidizing agent under visible light irradiationas a photosensitizer (Scheme and32). potassium As a photocatalyst, peroxydisulfate riboflavin as a issacrificial an inexpensive oxidizing natural agent reagent under visible that shows light irradiation (Scheme 32). As a photocatalyst, riboflavin is an inexpensive natural reagent that shows importantirradiation advances(Scheme over32). As transition-metal a photocatalyst, catalysis. riboflavin In addition,is an inexpensive the present natural method reagent accepted that ashows wide important advances over transition-metal catalysis. In addition, the present method accepted a wide scopeimportant of functional advances groupsover transition-metal and afforded catalysis. the desired In addition, productions. the present This environmentally method accepted friendly a wide scope of functional groups and afforded the desired productions. This environmentally friendly procedurescope of functional could be beneficialgroups and for pharmaceuticalafforded the desi uses.red productions. This environmentally friendly procedure could be beneficial for pharmaceutical uses. procedure could be beneficial for pharmaceutical uses.

SchemeScheme 32.32. Cyclization of thiobenzanilides under visible light. Scheme 32. Cyclization of thiobenzanilides under visible light. Scheme 32. Cyclization of thiobenzanilides under visible light. 2.2.2. Cyclization of CO2 as Raw Materials 2.2.2. Cyclization of CO2 as Raw Materials 2.2.2. Cyclization of CO2 as Raw Materials 2.2.2.Our Cyclization group of has CO reported2 as Raw Materials a newroute to synthesize benzothiazoles via cyclization of Our group has reported a new route to synthesize benzothiazoles via cyclization of 2-aminothiophenolsOur group has with reported CO2 in thea new presence route of diethylsilaneto synthesize catalyzed benzothiazoles by 1,5-diazabicyclo[4.3.0]non- via cyclization of 2-aminothiophenolsOur group has reportedwith CO a 2 newin routethe to presencesynthesize ofbenzothiazoles diethylsilane via catalyzedcyclization byof 5-ene2-aminothiophenols (DBN) at 5 MPa, with and variousCO2 benzothiazolesin the presence were achieved of indiethylsilane good yields (Schemecatalyzed 33 )[74by]. 2-aminothiophenols with CO2 in the presence of diethylsilane catalyzed by The mechanism research shows that hydrosilane played an important role in the formation of benzothiazoles and suppressed the production of benzothiazolones as the byproducts. This study provides an environmentally benign approach for the synthesis of benzothiazoles. Molecules 2020, 25, x 12 of 17 Molecules 2020, 25, x 12 of 17 Molecules 2020, 25, x 12 of 17 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) at 5 MPa, and various benzothiazoles were achieved in good 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) at 5 MPa, and various benzothiazoles were achieved in good yields1,5-diazabicyclo[4.3.0]non-5-ene (Scheme 33) [74]. The mechanism (DBN) atresearch 5 MPa, shows and various that hydrosilane benzothiazoles played were an importantachieved in role good in yields (Scheme 33) [74]. The mechanism research shows that hydrosilane played an important role in theyields formation (Scheme 33)of [74].benzothiazoles The mechanism and researchsuppressed shows the that production hydrosilane of played benzothiazolones an important as role the in the formation of benzothiazoles and suppressed the production of benzothiazolones as the byproducts.the formation This of studybenzothiazoles provides andan environmensuppressed tallythe productionbenign approach of benzothiazolones for the synthesis as theof byproducts. This study provides an environmentally benign approach for the synthesis of benzothiazoles.byproducts. This study provides an environmentally benign approach for the synthesis of benzothiazoles.Molecules 2020, 25, 1675 12 of 16 benzothiazoles.

Scheme 33. Cyclization of 2-aminothiophenols, CO2, and diethylsilane at 5 MPa. Scheme 33. Cyclization of 2-aminothiophenols, CO2, and diethylsilane at 5 MPa. Scheme 33. Cyclization of 2-aminothiophenols, CO2,, and and diethylsilane diethylsilane at 5 MPa. In addition, the cyclization of 2-aminobenzenethiol compounds with CO2 and hydrosilane to InIn addition, addition, the the cyclization cyclization of of 2-aminobenzenethiol 2-aminobenzenethiol compounds compounds with with CO CO2 and2 and hydrosilane hydrosilane to produceIn addition, a series theof benzothiazolescyclization of 2-aminobenzenethiol was discovered by compoundsour group underwith COmild2 and conditions hydrosilane using to produceto produce a series a series of ofbenzothiazoles benzothiazoles was was discovered discovered by by our our group group under under mild mild conditions using acetate-basedproduce a series ionic of liquid benzothiazoles as a catalyst was in high discovered yields (Scheme by our 34) group [75]. Weunder have mild also conditionsinvestigated using this acetate-based ionic liquid as a catalyst in high high yields yields (Scheme 34)34)[ [75].75]. We We have also investigated this reactionacetate-based under ionic different liquid conditionsas a catalyst with in high regard yields to (Scheme various 34) catalysts, [75]. We temperature, have also investigated and reaction this reaction underunder di differentfferent conditions conditions with with regard regard to various to various catalysts, catalysts, temperature, temperature, and reaction and pressure.reaction pressure.reaction underHere, different the best conditions results withwere regard obta toined various by catalysts,carrying temperature,out the reaction and reaction with pressure.Here, the bestHere, results the were best obtained results by carryingwere obta outined the reactionby carrying with 1-butyl-3-methylimidazolium out the reaction with 1-butyl-3-methylimidazoliumpressure. Here, the best acetateresults ([Bmim][OAc]) were obtained at 60 °Cby andcarrying 0.5 Mpa. ou Moreover,t the reactionthe reusability with 1-butyl-3-methylimidazoliumacetate ([Bmim][OAc]) at 60 Cacetate and 0.5 ([Bmim][OAc]) Mpa. Moreover, at 60 the °C reusabilityand 0.5 Mpa. of Moreover, [Bmim][OAc] the reusability was tested of1-butyl-3-methylimidazolium [Bmim][OAc] was tested as◦ acetatewell, and ([Bmim][OAc]) the yield of benzothiazoleat 60 °C and 0.5 almost Mpa. Moreover,stayed unchanged the reusability as the ofas [Bmim][OAc] well, and the was yield tested of benzothiazole as well, and almostthe yield stayed of benzothiazole unchanged almost as the ILstayed was unchanged reused five as times. the ILof was[Bmim][OAc] reused five was times. tested Notably, as well this, and is thethe yieldfirst protocolof benzothiazole for the synthesis almost stayed of benzothiazoles unchanged asusing the ILNotably, was reused this is five the firsttimes. protocol Notably, for this the synthesisis the first of protocol benzothiazoles for the usingsynthesis CO2 ofas benzothiazoles a raw material underusing COIL was2 as areused raw material five times. under Notably, metal-free this andis the mild first conditions. protocol for the synthesis of benzothiazoles using COmetal-free2 as a raw and material mild conditions. under metal-free and mild conditions. CO2 as a raw material under metal-free and mild conditions.

Scheme 34. Cyclization of 2-aminobenzenethiols with CO2 and hydrosilane at 0.5 MPa. Scheme 34. CyclizationCyclization of 2-aminobenzenethiols with CO 2 andand hydrosilane hydrosilane at at 0.5 0.5 MPa. MPa. Scheme 34. Cyclization of 2-aminobenzenethiols with CO2 and hydrosilane at 0.5 MPa. Chun and co-wokers [76] have reported that the synthesis of benzothiazoles from Chun and co-wokers [76] [76] have reported th thatat the synthesis of benzothiazoles from 2-aminobenzenethiolsChun and co-wokers and carbon [76] havedioxide reported in the presencethat the ofsynthesis 1,8-diazabicyclo[5.4.0]undec-7-ene of benzothiazoles from 2-aminobenzenethiols andand carbon carbon dioxide dioxide in thein presencethe presence of 1,8-diazabicyclo[5.4.0]undec-7-ene of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (DBU)at2-aminobenzenethiols 1 atm at of 1 COatm andof CO 60–70 2and and C carbon60–70 (Scheme °Cdioxide (Scheme35). The in reaction35).the presenceThe hadreaction a of broad 1,8-diazabicyclo[5.4.0]undec-7-enehad substrate a broad scopesubstrate and scope functional and (DBU) at 1 atm2 of CO2 and◦ 60–70 °C (Scheme 35). The reaction had a broad substrate scope and functional(DBU) at 1 group atm of tolerance. CO2 and Moreover,60–70 °C (Schemethe precatalyst 35). The salt reaction could behad recovered a broad substrateand reused scope several and functionalgroup tolerance. group Moreover,tolerance. theMoreover, precatalyst the saltprecatalyst could be salt recovered could be and recovered reused several and reused times withoutseveral timesfunctional without group any tolerance.loss of activity. Moreover, the precatalyst salt could be recovered and reused several timesany loss without of activity. any loss of activity. times without any loss of activity.

Scheme 35. Cyclization of 2-aminobenzenethiols and CO at 0.1 MPa. Scheme 35. Cyclization of 2-aminobenzenethiols and CO2 at 0.1 MPa. Scheme 35. Cyclization of 2-aminobenzenethiols and CO2 at 0.1 MPa. 3. Prospect for theScheme Further 35. Synthesis Cyclization of of Benzothiazoles 2-aminobenzenethiols and CO2 at 0.1 MPa. 3. Prospect for the Further Synthesis of Benzothiazoles 3. Prospect for the Further Synthesis of Benzothiazoles 3. ProspectEven though for the the Further research Synthesis on green of synthesis Benzothiazoles methods for benzothiazoles has made many advances, Even though the research on green synthesis methods for benzothiazoles has made many the developmentEven though of the mild research reaction on conditions green synthesi and inexpensives methods reactionfor benzothiazoles systems is stillhas amade challenging many advances,Even thethough development the research of mild on greenreaction synthesi conditionss methods and inexpensive for benzothiazoles reaction systemshas made is stillmany a advances,problem. Meanwhile,the development the development of mild reaction of reaction conditions systems and with inexpensive multiple reaction green reaction systems conditions is still a challengingadvances, the problem. development Meanwhile, of mild the reaction development conditions of reaction and inexpensive systems with reaction multiple systems green reactionis still a challengingstill needs to problem. be explored Meanwhile, by researchers. the development In the future, of reaction we will systems focus on with designing multiple and green developing reaction conditionschallenging still problem. needs Meanwhile,to be explored the bydevelopment researchers. of In reaction the future, systems we willwith focus multiple on designinggreen reaction and conditionseﬃcient, environmentally still needs to be friendly, explored and by economical researchers. reaction In the systems future, towe make will thefocus reaction on designing conditions and of developingconditions stillefficient, needs toenvironmentally be explored by friendly,researchers. and In economical the future, wereaction will focussystems on designingto make andthe developingexisting reaction efficient, pathways environmentally greener and thefriendly, reaction and process economical simpler, soreaction as to realize systems the industrializedto make the reactiondeveloping conditions efficient, of existingenvironmentally reaction pathwaysfriendly, greenerand economical and the reaction reaction process systems simpler, to make so as the to reactionpreparation conditions of benzothiazole of existing compounds reaction pathways and contribute greener to and the the development reaction process of green simpler, chemistry. so as to realizereaction theconditions industrialized of existing preparation reaction pathways of benzothiazole greener and compounds the reaction andprocess contribute simpler, soto asthe to realize the industrialized preparation of benzothiazole compounds and contribute to the developmentrealize the industrializedof green chemistry. preparation of benzothiazole compounds and contribute to the development4. Conclusions of green chemistry. development of green chemistry. In conclusion, this review has summarized recent advances in the synthesis of benzothiazoles

compounds related to green chemistry. In the past few decades, benzothiazoles have played a more and more important role in biochemistry and medicinal chemistry. As mentioned in this article, the condensation of 2-aminobenzenethiol with aldehydes/ketones/acids/acyl chlorides and the cyclization of thiamide or CO2 as raw materials have aroused more interest. Here, we have Molecules 2020, 25, 1675 13 of 16 strived to compile most of these methods recently reported to support the development of various synthetic benzothiazole derivatives involving green chemistry. This work is of great signiﬁcance for the development of synthetic pathways for benzothiazoles.

Author Contributions: X.G. and Y.G. formulated the research ideas. J.L., X.Z. and X.F. collected and organized relevant literatures. X.G. and J.L. wrote and edited the article. Y.G. revised the article. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by the Basic Research Plan of Natural Science in Shaanxi Province—General Project (Youth) (2018JQ2030, 2018JQ2028), the Outstanding Youth Science Fund of Xi’an University of Science and Technology (6310218022), and the PhD Start-up Fund of Xi’an University of Science and Technology (6310117053). Conﬂicts of Interest: The authors declare no conﬂicts of interest.

References

1. Carroll, A.R.; Scheuer, P.J. pentacyclic alkaloids from a tunicate and its prosobranch mollusk predator Chelynotus semperi. J. Org. Chem. 1990, 55, 4426–4431. [CrossRef] 2. Gunawardana, G.P.; Kohmoto, S.; Gunasekera, S.P.; McConnel, O.J.; Koehn, F.E. Dercitine, a new biologically active acridine alkaloid from a deep water marine sponge, Dercitus sp. J. Am. Chem. 1988, 110, 4856–4858. [CrossRef] 3. Noel, S.; Cadet, S.; Gras, E.; Hureau, C. The benzazole scaffold: A SWAT to combat Alzheimer’s disease. Chem. Soc. Rev. 2013, 42, 7747–7762. [CrossRef][PubMed] 4. Prajapati, N.P.; Vekariya, R.H.; Borad, M.A.; Patel, H.D. Recent advances in the synthesis of 2-substituted benzothiazoles: A review. RSC Adv. 2014, 4, 60176–60208. [CrossRef] 5. Kok, S.H.L.; Gambari, R.; Chui, C.H.; Yuen, M.C.W.; Lin, E.; Wong, R.S.M.; Lau, F.Y.; Cheng, G.Y.M.; Lam, W.S.; Chan, S.H.; et al. Synthesis and anti-cancer activity of benzothiazole containing phthalimide on human carcinoma cell lines. Bioorg. Med. Chem. 2008, 16, 3626–3631. [CrossRef] 6. Heo, Y.; Song, Y.S.; Kim, B.T.; Heo, J.N. A highly regioselective synthesis of 2-aryl-6-chlorobenzothiazoles employing microwave-promoted Suzuki–Miyaura coupling reaction. Tetrahedron. Lett. 2006, 47, 3091–3094. [CrossRef] 7. Alaimo, R.J.; Pelosi, S.S.; Freedman, R. Synthesis and Antibacterial Evaluation of 2-(Substituted Phenylureido)-4-thiocyanatobenzothiazoles. J. Pharm. Sci. 1978, 67, 281–282. [CrossRef] 8. Singh, M.; Singh, S.K.; Gangwar, M.; Nath, G.; Singh, S.K. Design, synthesis and mode of action of some benzothiazole derivatives bearing an amide moiety as antibacterial agents. RSC Adv. 2014, 4, 19013–19023. [CrossRef] 9. Caleta,´ I.; Grdiša, M.; Mrvoš-Sermek, D.; Cetina, M.; Tralić-Kulenovićd,V.; Pavelićb,K.; Karminski-Zamola, K. Synthesis, crystal structure and antiproliferative evaluation of some new substituted benzothiazoles and styrylbenzothiazoles. Il Farmaco. 2004, 59, 297–305. [CrossRef] 10. Das, J.; Moquin, R.V.; Lin, J.; Liu, C.; Doweyko, A.M.; Defex, H.F.; Fang, Q.; Pang, S.; Pitt, S.; Shen, D.R.; et al. Discovery of 2-amino-heteroaryl-benzothiazole-6-anilides as potent p56lck inhibitors. Bioorg. Med. Chem. 2003, 13, 2587–2590. [CrossRef] 11. Su, X.; Vicker, N.; Ganeshapillai, D.; Smith, A.; Purohit, A.; Reed, M.J.; Potter, B.V.L. Benzothiazole derivatives as novel inhibitors of human 11β-hydroxysteroid dehydrogenase type 1. Mol. Cell. Endocrinol. 2006, 248, 214–217. [CrossRef][PubMed] 12. Sreenivasa, G.M.; Jayachandran, E.; Shivakumar, B.; Jayaraj, K.K.; Vijay, K.M.M.J. Synthesis of bioactive molecule fluoro benzothiazole comprising potent heterocyclic moieties for anthelmintic activity. Arch. Pharm. Sci. Res. 2009, 1, 150–157. 13. Hutchinson, I.; Jennings, S.A.; Vishnuvajjala, B.R.; Westwell, A.D.; Stevens, M.F.G. Antitumor benzothiazoles. 16. Synthesis and pharmaceutical properties of antitumor 2-(4-aminophenyl) benzothiazole amino acid prodrugs. J. Med. Chem. 2002, 45, 744–747. [CrossRef][PubMed] 14. Bradshaw, T.D.; Westwell, A.D. The development of the antitumour benzothiazole prodrug, Phortress, as a clinical candidate. Curr. Med. Chem. 2004, 11, 1009–1021. [CrossRef][PubMed] 15. Yoshida, M.; Hayakawa, I.; Hayashi, N.; Agatsuma, T.; Oda, Y.; Tanzawa, F.; Iwasaki, S.; Koyama, K.; Furukawa, H.; Kurakata, S.; et al. Synthesis and biological evaluation of benzothiazole derivatives as potent antitumor agents. Bioorg. Med. Chem. Lett. 2005, 15, 3328–3332. [CrossRef][PubMed] Molecules 2020, 25, 1675 14 of 16

16. Vicini, P.; Geronikaki, A.; Incerti, M.; Busonera, B.; Poni, G.; Cabras, C.A.; Colla, P.L. Synthesis and biological evaluation of benzo [d] isothiazole, benzothiazole and thiazole Schiff bases. Bioorg. Med. Chem,. 2003, 11, 4785–4789. [CrossRef] 17. Nagarajan, S.R.; Crescenzo, G.A.; Getman, D.P.; Lu, H.F.; Sikorski, J.A.; Walker, J.L.; Mcdonald, J.J.; Houseman, K.A.; Kocan, G.P.; Kishore, N.; et al. Discovery of novel benzothiazole sulfonamides as potent inhibitors of HIV-1 protease. Bioorg. Med. Chem. 2003, 11, 4769–4777. [CrossRef] 18. Cressier, D.; Prouillac, C.; Hernandez, P.; Amourette, C.; Diserbo, M.; Lion, C.; Rima, G. Synthesis, antioxidant properties and radioprotective effects of new benzothiazoles and thiadiazoles. Bioorg. Med. Chem. 2009, 17, 5275–5284. [CrossRef] 19. Dogruer, D.S.; Ünlü, S.; ¸Sahin,M.F.; Yqilada, E. Anti-nociceptive and anti-inflammatory activity of some (2-benzoxazolone-3-yl and 2-benzothiazolone-3-yl) acetic acid derivatives. Il Farmaco. 1998, 53, 80–84. [CrossRef] 20. El-Sherbeny, M.A. Synthesis of certain pyrimido [2, 1-b] benzo-thiazole and benzothiazolo [2,3-b] quinazoline derivatives for in vitro antitumor and antiviral activities. Arzneimittelforschung. 2000, 50, 848–853. [CrossRef] 21. Jimonet, P.; Audiau, F.; Barreau, M.; Blanchard, J.C.; Boireau, A.; Bour, Y.; Coleno, M.A.; Doble, A.; Doerflinger, G.; Huu, C.D.; et al. Riluzole series. Synthesis and in vivo “antiglutamate” activity of 6-substituted-2-benzothiazolamines and 3-substituted-2-imino-benzothiazolines. J. Med. Chem. 1999, 42, 2828–2843. [CrossRef][PubMed] 22. Siddiqui, N.; Rana, A.; Khan, S.A.; Haque, S.E.; Alam, M.S.; Ahsan, W.; Ahmed, S. Anticonvulsant and Toxicity Evaluation of Newly Synthesized 1-[2-(3, 4-disubstituted phenyl)-3-chloro- 4-oxoazetidin-1-yl]-3-(6-substituted-1, 3-benzothiazol-2-yl) ureas. Acta Chim. Slov. 2009, 56, 462–469. 23. Rajeeva, B.; Srinivasulu, N.; Shantakumar, S.M. Synthesis and Antimicrobial Activity ofSome New 2-Substituted Benzothiazole Derivatives. J. Chem. 2009, 6, 775–779. [CrossRef] 24. Danzeisen, R.; Schwalenstoecker, B.; Gillardon, F.; Buerger, E.; Krzykalla, V.; Klinder, K.; Schild, L.; Hengerer, B.; Ludolph, A.C.; Dorner-Ciossek, C.; et al. Targeted antioxidative and neuroprotective properties of the dopamine agonist pramipexole and its nondopaminergic enantiomer SND919CL2x [(+) 2-amino-4, 5, 6, 7-tetrahydro-6-Lpropylamino-benzathiazole dihydrochloride]. J. Pharmacol. Exp. Ther. 2006, 316, 189–199. [CrossRef][PubMed] 25. Mylari, B.L.; Larson, E.R.; Beyer, T.A.; Zembrowski, W.J.; Aldinger, C.E.; Dee, M.F.; Siegel, T.W.; Singleton, D.H. Novel, potent aldose reductase inhibitors: 3,4-dihydro-4-oxo-3-[[5-(trifluoromethyl)-2-benzothiazolyl] methyl]-1-phthalazineacetic acid (zopolrestat) and congeners. J. Med. Chem. 1991, 22, 108–122. [CrossRef] 26. Bahrami, K.; Khodaei, M.M.; Naali, F. Mild and Highly Efficient Method for the Synthesis of 2-Arylbenzimidazoles and 2-Arylbenzothiazoles. J. Org. Chem. 2008, 73, 6835–6837. [CrossRef] 27. Panda, S.S.; Ibrahim, M.A.; Oliferenko, A.A.; Asiri, A.M.; Katritzky, A.R. Catalyst-free facile synthesis of 2-substituted benzothiazoles. Green Chem. 2013, 15, 2709–2712. [CrossRef] 28. Riadi, Y.; Mamouni, R.; Azzalou, R.; Haddadc, M.E.; Guillaumetd, S.R.G.; Lazara, S. An efficient and reusable heterogeneous catalyst animal bone meal for facile synthesis of benzimidazoles, benzoxazoles, and benzothiazoles. Tetrahedron. Lett. 2011, 52, 3492–3495. [CrossRef] 29. Sun, Y.; Jiang, H.; Wu, W.; Zeng, W.; Wu, X. Copper-catalyzed synthesis of substituted benzothiazoles via condensation of 2-aminobenzenethiols with nitriles. Org. Lett. 2013, 15, 1598–1601. [CrossRef] 30. Xiao, R.; Hao, W.; Ai, J.; Cai, M.Z. A practical synthesis of 2-aminobenzothiazoles via the tandem reactions of 2-haloanilines with isothiocyanates catalyzed by immobilization of copper in MCM-41. J. Org. Chem. 2012, 705, 44–50. [CrossRef] 31. Ma, D.; Lu, X.; Shi, L.; Zhang, H.; Jiang, Y.; Liu, X. Domino Condensation/S-Arylation/Heterocyclization Reactions: Copper-Catalyzed Three-Component Synthesis of 2-N-Substituted Benzothiazoles. Angew. Chem. Int. Ed. 2011, 50, 1118–1121. [CrossRef][PubMed] 32. Deng, H.; Li, Z.; Ke, F.; Zhou, X. Cu-Catalyzed Three-Component Synthesis of Substituted Benzothiazoles in Water. Chem. Eur. J. 2012, 18, 4840–4843. [CrossRef][PubMed] 33. Shi, L.; Liu, X.; Zhang, H.; Jiang, Y.; Ma, D. Synthesis of 2-Thio-Substituted Benzothiazoles via a Domino Condensation/S-Arylation/Heterocyclization Process. J. Org. Chem. 2011, 76, 4200–4204. [CrossRef] [PubMed] 34. Ding, Q.; Huang, X.G.; Wu, J. Facile Synthesis of Benzothiazoles via Cascade Reactions of 2-Iodoanilines, Acid Chlorides and Lawesson’s Reagent. J. Comb. Chem. 2009, 11, 1047–1049. [CrossRef] Molecules 2020, 25, 1675 15 of 16

35. Joyce, L.L.; Evindar, G.; Batey, R.A. Copper- and palladium-catalyzed intramolecular C-S bond formation: A convenient synthesis of 2-aminobenzothiazoles. Chem. Commun. 2004, 179, 446–447. [CrossRef] 36. Cheng, Q.; Peng, W.; Fan, P. Room-Temperature Ligand-Free Pd/C-Catalyzed C-S Bond Formation: Synthesis of 2-Substituted Benzothiazoles. J. Org. Chem. 2014, 79, 5812–5819. [CrossRef] 37. Sahoo, S.K.; Banerjee, A.; Chakraborty, S.; Patel, B.K. Regioselective intramolecular arylthiolations by ligand free cu and pd catalyzed reaction. ACS Catal. 2012, 2, 544–551. [CrossRef] 38. Qi, Y.; Ma, J.; Chen, X.; Xiu, F.R.; Chen, Y.; Lu, Y. Practical aptamer-based assay of heavy metal mercury ion in contaminated environmental samples: Convenience and sensitivity. Anal. Bioanal. Chem. 2020, 412, 439–448. [CrossRef] 39. Qi, Y.; Chen, Y.; Xiu, F.R.; Hou, J. An aptamer-based colorimetric sensing of acetamiprid in environmental samples: Convenience, sensitivity and practicability. Sens. Actuators B Chem. 2020, 304, 127359. [CrossRef] 40. Xiu, F.R.; Wang, Y.; Yu, X.; Li, Y.; Lu, Y.; Zhou, K.; He, J.; Song, Z.; Gao, X. A novel safety treatment strategy of DEHP-rich ﬂexible polyvinyl chloride waste through low-temperature critical aqueous ammonia treatment. Sci. Total Environ. 2020, 708, 134532. [CrossRef] 41. Xiu, F.R.; Lu, Y.; Qi, Y. DEHP degradation and dechlorination of polyvinyl chloride waste in subcritical water with alkali and ethanol: A comparative study. Chemosphere. 2020, 249, 126138. [CrossRef][PubMed] 42. Chen, Y.; Gao, X.; Liu, X.; Ji, G.; Fu, L.; Yang, Y.; Yu, Q.; Zhang, W.; Xue, X. Water collection from air by ionic liquids for eﬃcient visible-light-driven hydrogen evolution by metal-free conjugated polymer photocatalysts. Renew. Energ. 2020, 147, 594–601. [CrossRef]

43. Batista, R.M.; Costa, S.P.; Raposo, M.M.M. Synthesis of new ﬂuorescent 2-(20, 2”-bithienyl)-1, 3-benzothiazoles. Tetrahedron Lett. 2004, 45, 2825–2828. [CrossRef] 44. Guo, H.Y.; Li, J.C.; Shang, Y.L. A simple and eﬃcient synthesis of 2-substituted benzothiazoles catalyzed by

H2O2/HCl. Chin. Chem. Lett. 2009, 20, 1408–1410. [CrossRef] 45. Kumar, A.; Maurya, R.A.; Ahmad, P. Diversity oriented synthesis of benzimidazole and benzoxa/(thia) zole libraries through polymer-supported hypervalent iodine reagent. J. Combin. Chem. 2009, 11, 198–201. [CrossRef] 46. Maleki, B.; Salehabadi, H. Ammonium chloride; as a mild and efficient catalyst for the synthesis of some 2-arylbenzothiazoles and bisbenzothiazole derivatives. Eur. J. Chem. 2010, 1, 377–380. [CrossRef] 47. Praveen, C.; Nandakumar, A.; Dheenkumar, P.; Muralidharan, D.; Perumal, P. Microwave-assisted one-pot synthesis of benzothiazole and benzoxazole libraries as analgesic agents. J. Chem. Sci. 2012, 124, 609–624. [CrossRef] 48. Ye, L.; Chen, J.; Mao, P.; Mao, Z.; Zhang, X.; Yan, M. Visible-light-promoted synthesis of benzothiazoles from 2-aminothiophenols and aldehydes. Tetrahedron Lett. 2017, 58, 874–876. [CrossRef] 49. Maphupha, M.; Juma, W.P.; Koning, C.B.; Brady, D. A modern and practical laccase-catalysed route suitable for the synthesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles. RSC. Adv. 2018, 8, 39496–39510. [CrossRef] 50. Merroun, Y.; Chehab, S.; Ghailane, T.; Akhazzane, M.; Souizi1, A.; Ghailane, R. Preparation of tin-modified mono-ammonium phosphate fertilizer and its application as heterogeneous catalyst in the benzimidazoles and benzothiazoles synthesis. Reac Kine. Mech Cat. 2019, 126, 249–264. [CrossRef] 51. Bhat, R.; Karhale, S.; Arde, S.; Helavi, V. Acacia concinna pod catalyzed synthesis of 2-arylbenzothia/(oxa) zole derivatives. Iran. J. Catal. 2019, 9, 173–179. 52. Elderfield, R.C.; McClenachan, E.C. Pyrolysis of the Products of the Reaction of o-Aminobenzenethiols with Ketones1. J. Am. Chem. Soc. 1960, 82, 1982–1988. [CrossRef] 53. Liao, Y.; Qi, H.; Chen, S.; Jiang, P.; Zhou, W.; Deng, G.P. Efficient 2-Aryl Benzothiazole Formation from Aryl Ketones and 2-Aminobenzenethiols under Metal-Free Conditions. Org. Lett. 2012, 14, 6004–6007. [CrossRef] 54. Mayo, M.S.; Yu, X.; Zhou, X.; Feng, X.; Yamamoto, Y.; Bao, M. Convenient synthesis of benzothiazoles and benzimidazoles through Brønsted acid catalyzed cyclization of 2-amino thiophenols/anilines with β-diketones. Org. Lett. 2014, 16, 764–767. [CrossRef][PubMed]

55. Loukrakpam, D.C.; Phukan, P. TsNBr2 Mediated Synthesis of 2-Acylbenzothiazoles and Quinoxalines from Aryl Methyl Ketones under Metal Free Condition. Chemistry Select. 2019, 4, 3180–3184. 56. Gupta, S.D.; Singh, H.P.; Moorthy, N. Iodine-Catalyzed, One-Pot, Solid-Phase Synthesis of Benzothiazole Derivatives. Synth Commun. 2007, 37, 4327–4329. [CrossRef] 57. Rauf, A.; Gangal, S.; Sharma, S. Solvent-free synthesis of 2-alkyl and 2-alkenylbenzothiazoles from fatty acids under microwave irradiation. Indian J. Chem. 2008, 47, 601–605. [CrossRef] Molecules 2020, 25, 1675 16 of 16

58. Sharghi, H.; Asemani, O. Methanesulfonic acid/SiO2 as an efficient combination for the synthesis of 2-substituted aromatic and aliphatic benzothiazoles from carboxylic acids. Synth Commun. 2009, 39, 860–867. [CrossRef] 59. Coelho, F.L.; Campo, L.F. Synthesis of 2-arylbenzothiazoles via direct condensation between in situ generated 2-aminothiophenol from disulfide cleavage and carboxylic acids. Tetrahedron Lett. 2017, 58, 2330–2333. [CrossRef] 60. Nadaf, R.N.; Siddiqui, S.A.; Daniel, T.; Lahoti, R.J.; Srinivasan, K.V. Room temperature ionic liquid promoted regioselective synthesis of 2-aryl benzimidazoles, benzoxazoles and benzthiazoles under ambient conditions. J. Mol. Catal. A: Chem. 2004, 214, 155–160. [CrossRef] 61. Wu, C.; Wei, J.; Gao, K.; Wang, Y. Dibenzothiazoles as novel amyloid-imaging agents. Bioorg. Med. Chem. 2007, 15, 2789–2796. [CrossRef][PubMed] 62. Racané, L.; Kralj, M.; Šuman, L.; Stojkovićc,R.; Tralić-Kulenovićb,V.; Karminski-Zamola, G. Novel amidino substituted 2-phenylbenzothiazoles: Synthesis, antitumor evaluation in vitro and acute toxicity testing in vivo. Bioorg. Med. Chem. 2010, 18, 1038–1044. [CrossRef][PubMed]

63. Kumar, K.R.; Satyanarayana, P.V.V.; Reddy, B.S. NaHSO4-SiO2-Promoted Solvent-Free Synthesis of Benzoxazoles, Benzimidazoles, and Benzothiazole Derivatives. J. Chem. 2012, 2013, 1–10. [CrossRef] 64. Dar, A.A.; Shadab, M.; Khan, S.; Ali, N.; Khan, A.T. One-pot synthesis and evaluation of antileishmanial activities of functionalized S-alkyl/aryl benzothiazole-2-carbothioate scaffold. J. Org. Chem. 2016, 81, 3149–3160. [CrossRef] 65. Luo, B.; Li, D.; Zhang, A.L.; Gao, J. Synthesis, antifungal activities and molecular docking studies of benzoxazole and benzothiazole derivatives. Molecules. 2018, 23, 2457. [CrossRef] 66. Bose, D.S.; Idrees, M. Hypervalent Iodine Mediated Intramolecular Cyclization of Thioformanilides: Expeditious Approach to 2-Substituted Benzothiazoles. J. Org. Chem. 2006, 71, 8261–8263. [CrossRef] 67. Downer-Riley, N.K.; Jackson, Y.A. Conversion of thiobenzamides to benzothiazoles via intramolecular cyclization of the aryl radical cation. Tetrahedron. 2008, 64, 7741–7744. [CrossRef] 68. Rey, V.; Soria-Castro, S.M.; Argueello, J.E.; Peñéñory, A.B. Photochemical cyclization of thioformanilides by chloranil: An approach to 2-substituted benzothiazoles. Tetrahedron Lett. 2009, 50, 4720–4723. [CrossRef] 69. Feng, E.; Huang, H.; Zhou, Y.; Ye, D.; Jiang, H.; Liu, H. Metal-Free Synthesis of 2-Substituted (N, O, C) Benzothiazoles via an Intramolecular C S Bond Formation. J. Combin Chem. 2010, 12, 422–429. [CrossRef] − 70. Cheng, Y.; Yang, J.; Qu, Y.; Li, P. Aerobic visible-light photoredox radical C–H functionalization: Catalytic synthesis of 2-substituted benzothiazoles. Org. Lett. 2012, 14, 98–101. [CrossRef] 71. Folgueiras-Amador, A.A.; Qian, X.Y.; Xu, H.C.; Wirth, T. Catalyst-and supporting-electrolyte-free electrosynthesis of benzothiazoles and thiazolopyridines in continuous flow. Chem. Eur. J. 2018, 24, 487–491. [CrossRef][PubMed] 72. Xu, Z.M.; Li, H.X.; Young, D.J.; Zhu, D.L.; Li, H.Y.; Lang, J.P. Exogenous photosensitizer-, metal-, and base-free visible-light-promoted C–H thiolation via reverse hydrogen atom transfer. Org. Lett. 2018, 21, 237–241. [CrossRef][PubMed] 73. Bouchet, L.M.; Heredia, A.A.; Arguello, J.E.; Schmidit, L.C. Riboflavin as Photoredox Catalyst in the Cyclization of Thiobenzanilides: Synthesis of 2-Substituted Benzothiazoles. Org. Lett. 2019, 22, 610–614. [CrossRef]

74. Gao, X.; Yu, B.; Zhao, Y.; Hao, L.; Liu, C. Hydrosilane-promoted cyclization of 2-aminothiophenols by CO2 to benzothiazoles. RSC Adv. 2014, 4, 56957–56960. [CrossRef] 75. Gao, X.; Yu, B.; Yang, Z.; Zhao, Y.; Zhang, H.; Hao, L.; Han, B.; Liu, Z. Ionic liquid-catalyzed C–S bond

construction using CO2 as a C1 building block under mild conditions: A metal-free route to synthesis of benzothiazoles. ACS Catal. 2015, 5, 6648–6652. [CrossRef] 76. Chun, S.; Yang, S.; Chung, Y.K. Synthesis of benzothiazoles from 2-aminobenzenethiols in the presence of a reusable polythiazolium precatalyst under atmospheric pressure of carbon dioxide. Tetrahedron. 2017, 73, 3438–3442. [CrossRef]

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).