REVIEW ARTICLE


Synthetic Methods of Medicinally Important Heterocycles-thiazines: A Review



Praveen Kumar Sharma1, *, Andleeb Amin1, M. Kumar2
1 Department of Chemistry, School of Chemical Engineering and Physical Sciences, Lovely Professional University, Phagwara, Punjab, India
2 Department of Chemistry, University of Rajasthan, Jaipur, India

Article Information


Identifiers and Pagination:

Year: 2020
Volume: 14
First Page: 71
Last Page: 82
Publisher ID: TOMCJ-14-71
DOI: 10.2174/1874104502014010071

Article History:

Received Date: 03/05/2020
Revision Received Date: 04/08/2020
Acceptance Date: 05/08/2020
Electronic publication date: 22/09/2020
Collection year: 2020

Article Metrics

CrossRef Citations:
6
Total Statistics:

Full-Text HTML Views: 3447
Abstract HTML Views: 900
PDF Downloads: 861
Total Views/Downloads: 5208
Unique Statistics:

Full-Text HTML Views: 1529
Abstract HTML Views: 480
PDF Downloads: 659
Total Views/Downloads: 2668



Creative Commons License
© 2020 Sharma et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Chemistry, School of Physical Science, Lovely Professional University, Phagwara, Punjab, India; E-mail: pk_pandit1982@yahoo.com


Abstract

Heterocyclic compounds containing N and S atoms have unique properties so that they can be used as potential reactive materials in pharmacokinetic systems. In medicinal chemistry, the therapeutic applications of nitrogen sulphur heterocycles are well known. Especially, Thiazines attract the attention of chemists due to their great bioactive behavior. The present study is a review of the work carried out by the research community for the synthesis of novel, effective, medicinally important heterocyclic compounds-thiazines.

Keywords: Benzothiazines, Heterocycles, Thiazines, Pharmaceuticals, Phenothiazines, Heterocyclic compounds-thiazines.

1. INTRODUCTION

Studies of heterocycles, containing heteroatoms such as Sulphur and Nitrogen, are definitely one of the supreme targeted areas in heterocyclic chemistry. They are extensively used in several studies of natural products and pharmaceutical agent’s synthesis [1-3]. 1,4-Thiazine ring systems are considered a significant heterosystem in heterocyclic chemistry because it constitutes the skeleton of various natural products, such as conicaquinones A and B [4], the two cytotoxic terpene, quinones, xanthizone [5], and xanthiside [6] Fig. (1).

1, 4-Thiazine ring containing heterocycles is also known to play a vital role in pigments and dyestuffs [7, 8]. In addition to this, 4H-1,4-benzothiazines and their derivatives have been exposed to show wide ranging biological activities [9, 10] such as anticancer [11, 12], antifungal [13, 14], antagonistic [15], antioxidant [16], antihypertensive [17], analgesic [18], cardiovascular activity [19], antibacterial [20], antimalarial [21], antimicrobial [22], etc. Figs. (1-9).

The pharmaceutical/biological activities range of benzothiazines (4H-1,4-benzothiazines) has been recognized by the structural flexibility because of folding along N-S axis. The folding angle is affected to a larger degree by the arrangement of the substituents and nature. The basic features present in benzothiazines (4H-1,4-benzothiazines) hetero system are similar to that existing in 10H-phenothiazine, which marked them industrially as well as therapeutically interesting [23-48] (Figs. 10 and 11).

In the present time, human society comes in contact with different types of problems related to health and some of them are pandemic in nature. These problems arise in a short time period and are responsible for the loss of life on a large scale. In this type of situation, society put their eyes towards research communities , especially chemist, for providing solution either in terms of synthesis of new chemicals which can be used as potential medicinal material against said diseases, or production of existing chemical material in a short time period so that they never face the problem of shortage. Synthesis of new products is quite difficult and requires ample time for testing, clinical trials, and permissions from concerned authorities. Thus, chemists generally focus on the alternate synthetic methods of already tested chemical compounds. To overcome the challenge of synthesis time, researchers give more focus on the development of new methods through which the desired compound can be synthesized in a short time period without comprising on the environmental conditions. Thus, keeping this in mind, the main objective of the present article is to provide information to the research community regarding synthetic methods of most dominating heterocycles: thiazine ring systems.

Fig. (1). Xanthiside.

Fig. (2). Vasorelaxant.

Fig. (3). Antimalarial agent.

Fig. (4). Antibacterial agent.

Fig. (5). Antagonistic.

Fig. (6). Antibacterial against Neisseria gonorrhoea.

Fig. (7). Antimicrobial against Staphylococcus aureus.

Fig. (8). Natural Pigment.

Fig. (9). Antiviral against zika virus.

Fig. (10). Phenothiazine.

Fig. (11). 4H-1,4-Benzothiazine.

2. REVIEW OF LITERATURE

In view of continuing interest of the synthetic chemists in therapeutically interesting 1,4-benzothiazine hetero system(diverse biological activities and desirable pharmacokinetics) discovery, a variety of synthetic methods incorporating the preparation of benzothiazine especially 4H-1,4-benzothiazine skeleton, have been developed. Some of the important methods available in the literature and which have been widely used for the synthesis of 4H-1,4-benzothiazines are presented as:

T. Yamada et al. have reported a convenient way for the synthesis of benzothiazines(4H-1,4-benzothiazines) by the reaction of 2-amino-benzenethiols(3.8g) with ethyl 2-chloroacetoacetate (5.0g) with refluxing in ethanol for 30 minutes and cooling. Reaction products were further added to water (120ml) (Scheme 1). The collected precipitate was crystallized in methanol with 52% yield. [49, 50].

To overcome the problems of low yield, excess use of hazardous solvents, and more use of energy in previous methods, different groups of renowned researchers including R.R. Gupta et al., S. Kano et al., G. Liso et al., further extended above approach which was used for the synthesis of substituted benzothiazine, especially 4H-1,4-benothiazines, by the reaction of 2-aminobenzenthiol and their derivatives with different reactants, such as cyclohexan-1,3-dione, cyno-thiomethylacetophenone, acetylenic nitriles, and esters, in the presence of most suitable agent DMSO [51-53] (Schemes 2-4).

Scheme (1). Synthesis of Ethyl-3-methyl-4H-1,4-Benzothiazine.

Scheme (2). Synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol with cyclohexan-1,3-dione.

Scheme (3). Synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol with cyno-thiomethylacetophenone.

Scheme (4). Synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol with acetylenic nitriles.

In the same way, to increase the yield of product and reduce organic synthesis problem observed during the synthesis of most valuable nitrogen sulphur containing heterocycles, such as benzothiazines, A.Y. Chenko et al. and H. Nagase et al. used different approaches in which benzothiazines (4H-1,4-benzothiazines) have been prepared by the reaction of 2-aminobenzenethiol/sodium salt of N-substituted 2-aminobenzenethiols with bromoketones/phenacyl bromide [54,55] (Schemes 5-6).

Scheme (5). Synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol with bromo-ketones.

Scheme (6). Synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol with phenacyl bromide.

All the above methods are used for the synthesis of thiazine hetero systems. Due to organic synthesis complexity, regular use of hazardous chemicals, time-consumption, and lesser yield, these methods are phased out. To overcome all the above problems, Sheibani et al. have also reported the preparation of benzothiazines(4H-1,4-benzothiazines) by the following methods [56].

(a) The reaction of S-S dimer of 2-aminobenzenethiol with enaminones and esters in the presence of triethylamine provides 1,4-benzothiazines. In this reaction, nucleophilic addition of enaminones to disulphide of 2-aminobenzenethiol is followed by cyclization by Michael type addition of NH2 group to C=C bond to provide 1,4-benzothiazines (Schemes 7).

(b) Benzothiazines(4H-1,4- benzothiazines) have also been prepared by the reaction of alkylacetoacetates with disulphides in the presence of catalytic amounts of triethylamine (Schemes 8).

(c) The reaction of 2-aminobenzenthiols with β-diketones in the presence of H2O2/NaOH/H2O has also been reported for the preparation of 1,4-benzothiazines (Schemes 9).

(d) Sheibani et al. have also reported the reaction of acetylenic esters with 2-aminobenzenethiols for the preparation of 1,4-benzothiazines (Schemes 10).

V. Tandon et al. have stated ionic, liquid-assisted preparation of substituted 1,4-benzothiazines by the reaction of alkyl sulphanylamines with α-bromoacetylbromide. It was observed that the alkyl sulphanylamine with small alkyl groups are transformed into 1,4-benzothiazines easily with higher yields [57] (Schemes 11).

W. Zhang et al. have reported the synthesis of medicinally valuable benzothiazine (1, 4-benzothiazines) by the reaction of bis(o-nitrophenyl) disulphide with Kagan’s reagent [58] (Schemes 12).

M. Kumar et al. synthesized 1,4-benzothiazines incorporating chemical functionalities through a simple and appropriate regioselective synthesis involving the reaction of 2-aminobenzenthiols with diketone/ ketoester in the presence of dimethylsulfoxide. This method has been stated more suitable methods as previously reported methods used for the synthesis of 1,4-benzothiazines, as far as the yields of 1,4-benzothiazines are concerned [59-67] (Schemes 12-13).

Scheme (7). Synthesis of 4H-1,4-Benzothiazine by nucleophilic addition of enaminones to disulphide of 2-aminobenzenethiol.

Scheme (8). Synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol with alkylacetoacetates.

Scheme (9). Synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol with β-diketones in the presence of H2O2/NaOH/H2O.

Scheme (10). Synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol with acetylenic esters.

Scheme (11). Synthesis of 4H-1,4-Benzothiazine by the use of ionic liquids.

Scheme (12). Synthesis of 4H-1,4-Benzothiazine by the use of ionic liquids.

Scheme (13). Synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol with beta-di-ketones.

Mane et al. have extended this method to prepare 1,4-benzothiazines using hydrazine hydrate in the place of dimethyl sulfoxide under solvent-free conditions and reported that 2-aminobenzenthiol is oxidized by hydrazine, in the presence of air, into disulphide similarly as by dimethyl sulfoxide and undergoes cyclo condensation with diketones/ ketoesters involving in situ formation of enaminoketone as an intermediate [68] (Schemes 14).

Pratap et al. have designed a green, economical yet efficient synthesis of most biodynamical thiazine form:1,4-benzothiazines involving oxidative cycloaddition of 2-aminobenzothiol and 1,3-dicarbonyls in the presence of a cheaper biocatalyst baker’s yeast. Ultrasonication is also used to expedite the condensation process as it is responsible for the interference of the yeast cells for the fast discharge of the enzymes [69] (Schemes 15).

Scheme (14). Synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol with Phenyl hydrazine

Scheme (15). Synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol with beta-diketone in presence of Baker’s Yeast.

Scheme (16). Microwave assisted synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol.

Scheme (17). Microwave-assisted synthesis of 4H-1,4-Benzothiazine by the reaction of 2-aminobenzenethiol derivatives.

Paul et al. reported that aminobenzothiols and β-ketoester /β-diketones(using basic alumina as support under microwave irradiation) reacted with each other and produced medicinally important benzothiazines. The yield so obtained was found to vary in accordance with the amount of support taken and it was observed that maximum yields were obtained with 5-6 g of support versus 2mmol of the reagents [70] (Schemes 16).

Lizhi Fu et al. described a convenient method especially required in the synthesis of benzothiazines and their derivatives, which involves coupling between 2-amino-5-chlorophenyl disulphide and ethyl acetylenecarboxylate. The process is catalyzed using CuI or can be promoted via microwave irradiation, which expedites it and reduces the generation of by-products. Finally, the cyclization of the obtained compound with DMSO, followed by the oxidation using m-CPBA, afforded 4H-1,4-benzothiazines [71] (Schemes 17).

CONCLUSION

The overall aim of the review is to provide an idea, in detail, of novel methods used for the synthesis of medicinally important, biodynamic, and structurally diverse heterocycles. The present review article provides a platform for discovering important entities for pharmaceutical industries by new methods superior to the existing ones.

CONSENT FOR PUBLICATION

Not applicable.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

[1] Schreiber, S.L. Target-oriented and diversity-oriented organic synthesis in drug discovery. Science, 2000, 287(5460), 1964-1969.
[2] Teague, S.J.; Davis, A.M.; Leeson, P.D.; Oprea, T. The Design of Leadlike Combinatorial Libraries. Angew. Chem. Int. Ed. Engl., 1999, 38(24), 3743-3748.
[3] Armstrong, R.W.; Combs, A.P.; Tempest, P.A.; Brown, S.D.; Keating, T.A. Multiple-Component Condensation Strategies for Combinatorial Library Synthesis. Acc. Chem. Res., 1996, 29, 123-131.
[4] Aiello, A.; Fattorusso, E.; Luciano, P.; Menna, M.; Esposito, G.; Iuvone, T.; Pala, D. Conicaquinones A and B, Two Novel Cytotoxic Terpene Quinones from the Mediterranean Ascidian Aplidiumconicum. Eur. J. Org. Chem., 2003, 5, 898-900.
[5] Ma, Y.T.; Huang, M.C.; Hsu, F.L.; Chang, H.F. Thiazinedione from Xanthium strumarium. Phytochemistry, 1998, 48, 1083-1085.
[6] Mahmoud, A.A.; Ahmed, A.A.; Al-Shihry, S.S.; Spring, O. A new heterocyclic glucoside from the fruits of Xanthium pungens. Nat. Prod. Res., 2005, 19(6), 585-589.
[7] Stoodley, R.J.; Katritzky, A.R.; Boulton, A.J. Advances in Heterocyclic Chemistry; Eds, 1979, 24, 293-361.
[8] Cook, M.J.; Boulton, A.J.; McKillop, A., Eds.; Comprehensive Heterocyclic Chemistry; Eds, 1984, 3, 1037-1038.
[9] Ashok, D. Pallavi, K. Synthesis of 6-(6′-arylpyridin-2′-yl) and 6-(4\6′-diarylpyridin-2′-yl)- 3(4h)-oxo-l, 4-benzothiazines under microwave. Heterocycl. Commun., 2006, 12(3-4), 197-200.
[10] Galarreta, B.C.; Sifuentes, R. [REMOVED HYPERLINK FIELD] Amado, M.I.; Maruenda, H. The use of natural product scaffolds as leads in the search for trypanothionereductase inhibitors. Bioorg. Med. Chem., 2008, 16, 6689-6695.
[11] Hashimoto, T.; Amano, K.O.; Nakamura, Y.; Kanda, Y.; Kunii, S.; Motohashi, N.; Sakagami, H. Tumor-specific cytotoxicity andtype of cell death induced by benzocycloheptoxazines in humantumor cell lines. Anticancer, 2008, 28, 1069-1078.
[12] Morak-Mlodawska, B.; Pluta, K. Synthesis of Novel Dipyrido-1,4-thiazines. Heterocycles, 2007, 71, 1347-1361.
[13] Kamila, S.; Koh, B.; Zhang, H.; Biehl, E.R. Synthesis of (Z)-hetarylmethylene and (Z)-substituted benzylidene derivatives of 4H-benzo[1,4]thiazine-3-thiones and their subsequent conversion to benzothiopyrano-[3,2-b][1,4]benzothiazines. ARKIVOC, 2006, 2, 1-14.
[14] Jagath, R.G. SrinivasaRao, K; Khalilullah, Md.; Latha, D.; Thirupathaiah, C. synthesis of 9-arylthieno[3′,2′: 4,3]pyrimido[2,1-c][1,4] benzoxa/thiazines under microwave irradiation conditions. Heterocycl. Commun., 2005, 11, 195-198.
[15] Corelli, F.; Manetti, F.; Tafi, A.; Campiani, G.; Nacci, V.; Botta, M. Diltiazem-like calcium entry blockers: a hypothesis of the receptor-binding site based on a comparative molecular field analysis model. J. Med. Chem., 1997, 40(1), 125-131.
[16] Bakavoli, M.; Sadeghian, H.; Tabatabaei, Z.; Rezaei, E.; Rahimizadeh, M.; Nikpour, M. SAR comparative studies on pyrimido[4,5-b][1,4] benzothiazine derivatives as 15-lipoxygenase inhibitors, using ab initio calculations. J. Mol. Model., 2008, 14(6), 471-478.
[17] Fringuelli, R.; Milanese, L.; Schiaffella, F. Role of 1,4-benzothiazine derivatives in medicinal chemistry. Mini Rev. Med. Chem., 2005, 5(12), 1061-1073.
[18] Bhavani, N.; Perumal, S.; Banureka, R. Ethyl cis-3-(2-methoxyphenyl)-1-4-thiazine-2-carboxylate 1,1-dioxide at 150 K. Acta Cristallographica section E, 2003, 59(9), 1400-1402.
[19] Cecchetti, V.; Calderone, V.; Tabarrini, O.; Sabatini, S.; Filipponi, E.; Testai, L.; Spogli, R.; Martinotti, E.; Fravolini, A. Highly potent 1,4-benzothiazine derivatives as K(ATP)-channel openers. J. Med. Chem., 2003, 46(17), 3670-3679.
[20] Sabatini, S.; Kaatz, G.W.; Rossolini, G.M.; Brandini, D.; Fravolini, A. From phenothiazine to 3-phenyl-1,4-benzothiazine derivatives as inhibitors of the Staphylococcus aureus NorA multidrug efflux pump. J. Med. Chem., 2008, 51(14), 4321-4330.
[21] Barazarte, A.; Camacho, J.; Domínguez, J.; Lobo, G.; Gamboa, N.; Rodrigues, J.; Capparelli, M.V.; Alvarez-Larena, A.; Andujar, S.; Enriz, D.; Charris, J. Synthesis, antimalarial activity, structure-activity relationship analysis of thieno-[3,2-b]benzothiazine S,S-dioxide analogs. Bioorg. Med. Chem., 2008, 16(7), 3661-3674.
[22] Mandour, A.H.; El-Sawy, E.R.; Ebid, M.S.; El-Sayed, Z.G. Egypt. J. Chem., 2007, 50, 555-568.
[23] Sharma, P.K.; Kumari, M. Study of ethyl acetoacetate, 2-aminobenzenethiol and ceric ammonium nitrate composition for biopharmaceutical applications. J. Phys. Conf. Ser., 2020, 1531012096
[24] Grandolini, G.; Tiralti, M.C.; Rossi, C.; Ambrogi, V.; Orzalesi, G.; De Regis, M. Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines. II. Synthesis of new series of 1- or 2-substituted 4H-s-triazolo[3,4-c]-1,4-benzothiazines and related compounds with potential CNS activity. Farmaco, Sci., 1987, 42(1), 43-60.
[25] Sharma, P.K.; Saroha, S. Study of Heterocyclic Ring Systems: Biopharmaceutical Applications of Substituted 4H-1,4-Benzothiazine and Piperazine. J. Phys. Conf. Ser., 2020, 1531012094
[26] Rai, D.; Gupta, V.; Gupta, R.R. Synthesis of 4-(n-alkyl/aryl-n-nitrosoamido)-2, 3-dihydro-1, 4-benzothiazines. Heterocycl. Commun., 1996, 2, 273-274.
[27] Kwon, S.K.; Park, M.S. Some new 1,2-benzothiazine derivatives with analgesic and anti-inflammatory activities. Arzneimittelforschung, 1996, 46(10), 966-971.
[28] Oren, D.A.; Zhang, A.; Nesvadba, H.; Rosenwirth, B.; Arnold, E. Synthesis and activity of piperazine-containing antirhinoviral agents and crystal structure of SDZ 880-061 bound to human rhinovirus 14. J. Mol. Biol., 1996, 259(1), 120-134.
[29] Palagiano, F.; Arenare, L.; De Caprariis, P.; Grandolini, G.; Ambrogi, V.; Perioli, L.; Filippelli, W.; Falcone, G.; Rossi, F. Synthesis and SAR study of imidazo[2,1-b]benzothiazole acids and some related compounds with anti-inflammatory and analgesic activities. Farmaco, 1996, 51(7), 483-491.
[30] Matsuoka, H.; Ohi, N.; Mihara, M.; Suzuki, H.; Miyamoto, K.; Maruyama, N.; Tsuji, K.; Kato, N.; Akimoto, T.; Takeda, Y.; Yano, K.; Kuroki, T. Antirheumatic agents: novel methotrexate derivatives bearing a benzoxazine or benzothiazine moiety. J. Med. Chem., 1997, 40(1), 105-111.
[31] Gadó, K.; Gigler, G. Zymosan inflammation: a new method suitable for evaluating new antiinflammatory drugs. Agents Actions, 1991, 32(1-2), 119-121.
[32] Kulkarni, N.; Zang, E.; Kelloff, G.; Reddy, B.S. Effect of the chemopreventive agents piroxicam and D,L-alpha-difluoromethylornithine on intermediate biomarkers of colon carcinogenesis. Carcinogenesis, 1992, 13(6), 995-1000.
[33] Nagashima, S.; Uematsu, T.; Araki, S.; Matsuzaki, T.; Fukuchi, M.; Hashimoto, H.; Nakashima, M. Antiarrhythmic and electrophysiological effects of SD-3212, a novel Na+ and Ca++ channel blocker, in anaesthetized dogs with myocardial infarction in comparison with its stereoisomer (SD-3211) and bepridil. Naunyn Schmiedebergs Arch. Pharmacol., 1992, 345(6), 688-695.
[34] Sharma, P.K. Synthesis of Starting Heterocycles: 2-Aminobenzothiazoles, 2-Aminothiazoles and 2-Aminobenzenethiols – Potential Precursors for Macroheterocycles. Macroheterocycles, 2018, 11(3), 316-321.
[35] Varga, J.M.; Kalchschmid, G.; Klein, G.F.; Fritsch, P. Mechanism of allergic cross-reactions--I. Multispecific binding of ligands to a mouse monoclonal anti-DNP IgE antibody. Mol. Immunol., 1991, 28(6), 641-654.
[36] Metwally, M.A.; El-Hossini, M.; El-Alblak, F.Z.; Khalil, A.M. Synthesis of condensed heterocycles from 3-aryl-2,4-dicarbethoxy-5-methylcyclohexanones and their testing for antimicrobial activity. Pharmazie, 1999, 47(5), 336-339.
[37] Li, H.; Dryhurst, G. Irreversible inhibition of mitochondrial complex I by 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxyli c acid (DHBT-1): a putative nigral endotoxin of relevance to Parkinson’s disease. J. Neurochem., 1997, 69(4), 1530-1541.
[38] Kobayashi, T.; Strobeck, M.; Schwartz, A.; Mori, Y. Inhibitory effects of a new neuroprotective diltiazem analogue, T-477, on cloned brain Ca2+ channels expressed in Xenopus oocytes. Eur. J. Pharmacol., 1997, 332(3), 313-320.
[39] Koidl, B.; Miyawaki, N.; Tritthart, H.A. A novel benzothiazine Ca2+ channel antagonist, semotiadil, inhibits cardiac L-type Ca2+ currents. Eur. J. Pharmacol., 1997, 322(2-3), 243-247.
[40] Studenik, C.; Lemmens-Gruber, R.; Heistracher, P. New benzoxazine and benzothiazine derivatives--structure-activity relations in guinea-pig heart and smooth muscle preparations. Pharmazie, 1999, 54(5), 330-334.
[41] Kumar, M.; Sharma, N.; Gupta, R.; Gupta, R.R. One pot synthesis of 7-fluoro-5-methyl-4h-1, 4-benzothiazines. Heterocycl. Commun., 1998, 4(2), 187-190.
[42] Chaudhari, B.R.; Shinde, D.B.; Shingare, M.S. Indian J. Heterocycl. Chem., 1995, 4(3), 187-190.Chem. Abstr., 1995, 123256553
[43] Reddy, B.S.; Tokumo, K.; Kulkarni, N.; Aligia, C.; Kelloff, G. Inhibition of colon carcinogenesis by prostaglandin synthesis inhibitors and related compounds. Carcinogenesis, 1992, 13(6), 1019-1023.
[44] Deshmukh, M.B.; Mulik, A.R.; Desal, S.D. Synthesis of some new 2-methyl-1, 4-benzothiazine-3(1H)-one derivatives as potential vasodilators. E-J. Chem., 2004, 1, 206-210.
[45] Kumar, G.; Gupta, V.; Gautam, D.C.; Gupta, R.R. A convenient synthesis of 5/7-chloro-4H-1, 4-benzothiazines. Heterocycl. Commun., 2002, 8(4), 381-384.
[46] Patil, L.R.; Bondge, S.P.; Bhingolikas, U.E.; Mane, R.A. Synthesis and microbial activity of new 1,4-benzothiazines bearing paracetamol moiety. Indian J. Chem, 2002, 41 B(7), 1513, 1515.
[47] Kachhee, T.L.; Gupta, V.; Gupta, R.; Gautam, D.C. Synthesis of 7-ethoxy-3-methyl-4h-1, 4-benzothiazines. Heterocycl. Commun., 2002, 8(6), 579-582.
[48] Sharma, P.K. A review: Different approach of bioactive pyrimidobenzothiazoles synthesis. Drug Invention Today, 2017, 9(3), 18-22.
[49] Maki, Y.; Suzuki, M.; Yamada, T. Reactions of ethyl 3-methyl-4H-benzo-1,4-thiazine-2-carboxylate with hydrazine derivatives. Chem. Pharm. Bull. (Tokyo), 1966, 14(7), 770-772.
[50] Duro, F.; Condarilli, P.; Ronsisvalle, G. 1, 4-Benzothiazine. Ann. Chim., 1973, 63, 45-54.
[51] Gupta, R.R.; Kalwania, G.S.; Kumar, R. Single Step Synthesis of 4 H-1, 4-Benzothiazines. Bull. Chem. Soc. Jpn., 1984, 57(8), 2343-2344.
[52] Kano, S.; Yuasa, Y.; Ono, T.; Shibuya, S. Synthesis of 4H-1,4-benzothiazine derivatives through condensation of o-aminothiophenol with α-cyano-α-methylthioacetophenones. Heterocycles, 1979, 12, 681-684.
[53] Liso, G.; Trabani, G.; Berardi, V.; Latrofa, A.; Marchini, P. Adducts of 2‐aminothiophenol with acetylenic nitriles or esters and their conversion into benzothiazoles and/or 1, 4‐benzothiazines. J. Heterocycl. Chem., 1980, 17(4), 793-796.
[54] Sharma, P.K. A review on antimicrobial activities of important thiazines based heterocycles. Drug Invention Today, 2017, 9(3), 23-25.
[55] Nagase, H. Studies on fungicides. XXIV. Reaction of 5-methoxycarbonyl-methylidene-2-thioxo(or oxo)-4-thiazolidones with o-aminobenzenethiol and other thiols. Chem. Pharm. Bull. (Tokyo), 1974, 22(1), 42-49.
[56] aIslami, M.R.; Mollazehi, F.; Badiei, A.; Sheibani, H. Serendipitous synthesis of 1,4-benzothiazin derivatives using 2-[(2-aminophenyl)disulfanyl]aniline. ARKIVOC, 2005, xv, 25-29.bIslami, M.R.; Nassab, F.H.; Badiei, A.; Sheibani, H.; Hassanpour, A. Nucleophilic addition of enaminones to the S-S dimer of 2-aminobenzenethiol. ARKIVOC, 2006, xv, 175-180.cIslami, M.R.; Hosseininasab, F.; Badiei, A.; Sheibani, H.; Hassanpour, A. Nucleophilic substitution of 2,2′-disulfanediyldianiline by β-keto esters and 1,3-diketones in the presence of triethylamine. ARKIVOC, 2006, xv, 68-75.dSheibani, H.; Islami, M.R.; Hassanpour, A.; Saidi, K. One-pot multi-component approach to the synthesis of 1, 4-benzothiazines in aqueous media. Phosphorus. Sulfur Relat. Elem., 2007, 183(1), 13-20.
[57] Chhikara, B.S.; Mishra, A.K.; Tandon, V. KF-alumina immobilized in ionic liquids: A novel heterogeneous base for heterocyclization of alkylsulfanylphenylamines into 1, 4-benzothiazine. Heterocycles, 2004, 63(5), 1057-1065.
[58] Zhong, W.; Zhang, Y. Synthesis of 2H-1, 4-benzothiazin-3 (4H)-ones and 2H-1, 4-benzoselenazin-3 (4H)-ones with the aid of samarium (II) iodide. Tetrahedron Lett., 2001, 42(17), 3125-3127.
[59] Armenise, D.; Trapani, G.; Arrivo, V.; Morlacchi, F. Preparation of potentially bioactive aza and thiaza polycyclic compounds containing a bridgehead nitrogen atom. Synthesis of pyrrolo [1, 2, 3‐de]‐1, 4‐benzothiazine derivatives. J. Heterocycl. Chem., 1990, 27(6), 1521-1525.
[60] Gupta, R.R.; Saraswat, V.; Gupta, A.; Jain, M.; Gupta, V. Studies on phenothiazines. Part 16. Synthesis and spectral studies of substituted 1, 2‐dichlorophenothiazines. J. Heterocycl. Chem., 1992, 29(7), 1703-1707.
[61] Gupta, R.R.; Rathore, R.K.; Gupta, V.; Rathore, R.S. A single step synthesis of 6-bromo-2, 3-disubtituted-4H-1, 4-benzothiazines. Pharmazie, 1991, 46(8), 602.
[62] Gupta, R.R.; Jain, M.; Rathore, R.S.; Gupta, A. Synthetic and spectral investigation of fluorinated phenothiazines and 4H-1, 4-benzothiazines as potent anticancer agents. J. Fluor. Chem., 1993, 62(2-3), 191-200.
[63] Gupta, A.; Saraswat, V.; Gupta, S.K.; Mukherji, S.K.; Gupta, R.R. Synthesis of 5,8-dichloro-3-methyl-4h-1,4- benzothiazines and their conversion into sulfones. Phosphorus Sulfur, 1993, 85, 101-106.
[64] Thomas, L.; Gupta, A.; Gupta, V. Synthesis of 2-amino-5-chloro-3-(trifluoromethyl)benzenethiol and conversion into 4H-1,4-benzothiazines and their sulfones. J. Fluor. Chem., 2003, 122(2), 207-213.
[65] Yoshimoto, M.; Ishida, N.; Hiraoka, T. A new general method for carbon-carbon condensation of conjugated enaminoketones at the γ-position. Tetrahedron Lett., 1973, 14(1), 39-42.
[66] Rathore, B.S.; Kumar, M. Synthesis of 7-chloro-5-trifluoromethyl/7-fluoro/7-trifluoromethyl-4H-1,4-benzothiazines as antimicrobial agents. Bioorg. Med. Chem., 2006, 14(16), 5678-5682.
[67] aSharma, P.K. Antifungal, Antibacterial and Antioxidant activities of substituted Morpholinylbenzothiazine. Pharma Chemica, 2016, 8(11), 140-142.bSharma, P.K. Antibacterial, Antifungal and Antioxidant activities of substituted pyrazolylbenzothiazines. Der Pharma Chemica. 2016, 8(11), 79-82.cSharma, P.K. Antibacterial, Antifungal and Antioxidant activities of substituted 4H-1,4-benzothiazines. Der Pharma Chemica. 2016, 8(11), 156-159.dSharma, P.K. Antibacterial and Antifungal activity of Piperazinylbenzothiazine. Pharma Chem., 2016, 8(5), 191-193.eSharma, P.K. Antifungal, Antibacterial and Antioxidant activities of substituted Morpholinylbenzothiazine. Der Pharmacia Lettre, 2016, 8(4), 86-90.fSharma, P.K.; Kumar, M. Synthesis of bioactive substituted pyrazolylbenzothiazinones. Res. Chem. Intermed., 2015, 41(9), 6141-6148.gSharma, P.K.; Kumar, M. Antimicrobial and antioxidant activities of substituted 4H-1, 4-benzothiazines. Med. Chem. Res., 2012, 21(8), 2072-2078.hSharma, P.K.; Kumar, M. Synthesis and antimicrobial activity of structurally flexible heterocycles with the 1, 4-thiazine heterosystem. Res. Chem. Intermed., 2011, 37(8), 1103-1111.iSharma, P.K.; Kumar, M. Synthesis and antimicrobial activity of 2H-pyrimido [2,1-b]benzothiazol-2-ones. Res. Chem. Intermed., 2010, 36(8), 985-993.jSharma, P.K.; Kumar, M. One-pot, multicomponent sequential synthesis of benzothiazoloquinazolinones. Synth. Commun., 2010, 40(16), 2347-2352.kSharma, P.K.; Kumar, M. N-bridged heterocycles: regiospecific synthesis of 2-methyl-4H-pyrimido [2, 1-b] benzothiazol-4-ones. Res. Chem. Intermed., 2009, 35(1), 35-42.lSharma, P.K.; Kumar, M. Regioselective OnePot Synthesis Of 5-Chloro-3-Methyl-8-Trifluoromethyl-4H-1, 4-Benzothiazines. Heterocycl. Commun., 2009, 15(2), 127-134.mSharma, P.K.; Kumar, G. Synthesis, spectral, energetic and reactivity properties of phenothiazines: Experimental and computational approach. J. Chem. Pharm. Res., 2015, 7(11), 462-473.
[68] Munde, S.B.; Bondge, S.P.; Bhingolikar, V.E.; Mane, R.A. A facile synthesis of 1,4-benzothiazines under solvent free conditions. Green Chem., 2003, 5(2), 278-279.
[69] Pratap, U.R.; Jawale, D.V.; Londhe, B.S.; Mane, A.R. Baker’s yeast catalysed synthesis of 1,4- benzothiazines, performed under ultrasonication. J. Mol. Catal., B Enzym., 2011, 68, 94-97.
[70] Paul, S.; Gupta, R.; Loupy, A.; Rani, B.; Dandia, A. Dry media synthesis of 4H-1, 4- Benzothiazines under microwave irradiation using basic alumina as solid support. Synth. Commun., 2001, 31(5), 711-717.
[71] Fu, L. Xu, J.; Yao, H.; Wu, X. A synthesis of 4H-1, 4-benzothiazines. J. Chem. Res., 2008, 10, 566-567.