Modern Approaches to the Synthesis and Transformations of Practically Valuable Benzothiazole Derivatives

Abstract

The review is devoted to modern trends in the chemistry of 2-amino and 2-mercapto substituted benzothiazoles covering the literature since 2015. The reviewed heterocycles belong to biologically active and industrially demanded compounds. Newly developed synthesis methods can be divided into conventional multistep processes and one-pot, atom economy procedures, realized using green chemistry principles and simple reagents. The easy functionalization of the 2-NH₂ and 2-SH groups and the benzene ring of the benzothiazole moiety allows considering them as highly reactive building blocks for organic and organoelement synthesis, including the synthesis of pharmacologically active heterocycles. The review provides a summary of findings, which may be useful for developing new drugs and materials and new synthetic approaches and patterns of reactivity.

Keywords: 2-aminobenzothiazole; 2-mercaptobenzothiazole; benzothiazole; biological activity; reactivity; synthesis.

Scheme 1

Ru(III)-catalyzed synthesis of substituted 2-aminobenzothiazoles from N-arylthioureas.

Scheme 2

Pd-catalyzed synthesis of 2-(dialkylamino)benzothiazoles from N-aryl-N’,N’-dialkylthioureas.

Scheme 3

Ni(II)-catalyzed synthesis of 2-aminobenzothiazoles 3a–t from N-arylthioureas.

Scheme 4

Synthesis of 2-aminobenzothiazoles 4a–m from 2-haloanilines and dithiocarbamates.

Scheme 5

Synthesis of 2-aminobenzothiazoles 5a–u from arylisothiocyanates and formamides.

Scheme 6

Synthesis of 2-aminobenzothiazoles from arylthioisocyanates and amines.

Scheme 7

Synthesis of 2-aminobenzothiazoles 7a–v from iodoanilines and sodium dithiocarbamates.

Scheme 8

Synthesis of 2-aminobenzothiazoles 8a–d from aminothiophenols and thiocarbamoyl chloride.

Scheme 9

Synthesis of 2-aminobenzothiazoles 9a–z from haloanilines and thiocarbamoyl chloride.

Scheme 10

Synthesis of 2-aminobenzothiazoles 10a–c from benzothiazole and O-benzoylhydroxylamines.

Scheme 11

Three-component synthesis of 2-aminobenzothiazoles 11a–v.

Scheme 12

Synthesis of the ring-substituted N-acylated 2-aminobenzothiazoles 12a–u.

Scheme 13

Synthesis of the uracil-containing N-benzothiazolyl benzamides 13a–i with herbicide activity.

Scheme 14

Mono- and dialkylation of 2-aminobenzthiazoles by 7-chloro-4,6-dinitrobenzofuroxane.

Scheme 15

Synthesis of antidepressant heterocycles 16a–v.

Scheme 16

Synthesis of benzothiazolyl-piperazine heterocycles 17a–t with insecticide activity.

Scheme 17

Synthesis of polyheterocyclic acetamides 18a–t.

Scheme 18

Multistep syntheses of 2-aminobenzothiazole analogs of clathrodine 19a–f.

Scheme 19

Synthesis of 1-benzothiazolyl-3-aryl-4-formyl-1H-pyrazoles 20a–k.

Scheme 20

Synthesis of benzothiazole-containing sulfanilamide derivatives 21–23.

Scheme 21

Synthesis of functionalized bis-thiazolo derivatives 24a–d and 25a–e.

Scheme 22

Multistep synthesis of benzothiazole/semicarbazone/disulfoxide-containing products 26a–x with antibacterial properties.

Scheme 23

Synthesis of bis-thiazolo-containing amines 27a–d and azomethines 28a–k.

Scheme 24

Schiff base 29 from 2-amino-6-nitrobenzothiazole and 3,5-diiodosalicylic aldehyde.

Scheme 25

Synthesis of 6-N-functionalized derivatives of 2-aminobenzothiazoles 30–32.

Scheme 26

Synthesis of new benzothiazole-disulfonamide scaffolds 33a–n as viral inhibitors.

Scheme 27

Synthesis of benzothiazole-imidazolidines 34a–h.

Scheme 28

New potent cytotoxic hybrid azolyl derivatives of benzothiazole 35a–c and 36a–g.

Scheme 29

Synthesis of 3-phenoxybenzo[d]imidazo[2,1-b]thiazoles 37a–e.

Scheme 30

Atom-economy green synthesis of benzothiazole-quinazolinones 38a–i.

Scheme 31

Three-component synthesis of polycyclic 3-aminoimidazo[2,1-b](1,3)-benzothiazoles 39a–l.

Scheme 32

Three-component synthesis of 4H-pyrimido[2,1-b]benzothiazoles 40a–m.

Scheme 33

Three-component synthesis of quinazoline derivatives of 2-aminobenzothiazole 41a–f.

Scheme 34

Synthesis of spiroheterocycle 42 from 2-amino-6-bromo-4-methylbenzothiazole, 4-anisaldehydeгидa and 4-hydroxycoumarine.

Scheme 35

Synthesis of tricyclic derivatives of imidazo[2,1-b](1,3)benzothiazolones 43a–k.

Scheme 36

MW-assisted, catalyst-free synthesis of benzo[d]imidazo[2,1-b]thiazoles 44a–l.

Scheme 37

Synthesis of benzothiazole hydrazones with 2-anilinopyridyl groups 45a–v.

Scheme 38

Synthesis of antimalarial 2-benzothiazolyl hydrazones 46a–f.

Scheme 39

Synthesis of benzothiazole-triazole compounds 47a–n.

Scheme 40

Synthesis of 2-aminonicotine nitriles 48a–f having the benzothiazole fragment.

Scheme 41

2-Mercaptobenzothiazoles 49a,b from aminothiophenols and tetramethylthiuram disulfide or sodium dimethyl dithiocarbamate.

Scheme 42

Mercaptobenzothiazoles 50a–c from N-thioacylbenzotriazoles in the presence of PMHS.

Scheme 43

Synthesis of precursors of 2-mercaptobenzothiazoles 51a–n from 2-halogenoanilines and potassium xanthogenate and their further functionalization.

Scheme 44

CuBr-catalyzed synthesis of 2-mercaptobenzothiazoles 54a–g from o-aminothiophenols, tetramethylthiuram disulfide and iodobenzenes.

Scheme 45

Benzothiazolethiones 55a–y from o-iodoanilines, K₂S and (tosylmethyl)isocyanide.

Scheme 46

Oxidative synthesis of 2-arylthiobenzothiazoles from benzothiazoles, elemental sulfur and arylboronic acids.

Scheme 47

Synthesis of 2-(arylthio)benzothiazoles 57a–w via photoinduced sulfanylation.

Scheme 48

Nano-Fe₃O₄ promoted synthesis of 2-(arylthio)benzothiazoles 58a–e.

Scheme 49

The synthesis of benzothiazol-2-yl sulfides 59 from benzothiazole, triphenylphosphine and S-nucleophiles.

Scheme 50

Base-free S-arylation of 2-mercaptobenzothiazole with diaryliodonium triflates.

Scheme 51

KI/K₂S₂O₈-promoted S-acylmethylation of 2-mercaptobenzothiazole with ketones.

Scheme 52

Sequence of reactions 2-mercaptobenzothiazole → thioethers 62a–n → sulfones 63a–n → sulfinate salts.

Scheme 53

Different protocols for synthesizing biologically active sulfones 65a–k.

Scheme 54

Multistep synthesis of anti-inflammatory mercaptobenzothiazole-1,2,4-oxadiazoles 66a–h and their benzamide analogs 67a–k.

Scheme 55

Synthesis of benzothiazole-1,2,3-triazole compounds 68a–s.

Scheme 56

Multistep synthesis of benzothiazole-1,3,4-oxadiazole heterocycles 71a–e having anti-inflammatory, antimicrobial and antioxidant activity.

Scheme 57

Synthesis of lactames 73a–m and their precursors 72a–m from 2-mercaptobenzothiazole.

Scheme 58

Synthesis of benzothiazolyl acyl hydrazones 74a–j with antitumor activity.

Scheme 59

Synthesis of scaffolds 75, 76 from 2-mercaptobenzothiazole and 4,6,7-substituted 2,1,3-benzoxadiazole 1-oxides.

Scheme 60

Benzothiazolyl furfuryl sulfides 77a–d via cyclization of 2-mercaptobenzothiazole with aryl enyne ketones.

Scheme 61

Organosilicon salts 78, 79 and disulfonium dications 80 from 2-mercaptobenzothiazole.

Scheme 62

Annulation with rearrangement of salt 79a to salt 81.

Scheme 63

Synthesis of bis-iminium salt 82 from 2-mercaptobenzothiazole and iodomethylsiloxanes.

Scheme 64

Synthesis of non-salt forms of silicon-aromatic, silicon-acetylenic, and siloxane derivatives of 2-mercaptobenzothiazole 83a–c, 84.

Scheme 65

Acylalkylation and annulation reactions of 2-mercaptobenzothiazole derivatives with iodoacetone.

Scheme 66

Synthesis of trimethoxysilyl and trifluorosilyl derivatives of 2-mercaptobenzothiazole.

Scheme 67

Sol–gel synthesis of anticorrosion coating 91 based on 2-mercaptobenzothiazole.

Scheme 68

Preparation of nanosorbent 92 based on magnetic GO and 2-mercaptobenzothiazole.