1.3.4- Thiadiazepines

A similar regiospecific [2 -I- 2] cycloaddition across a C=S group occurred when benzoyl isothiocyanate (436) and 2,3-diphenyl-1-azirine were heated in refiuxing benzene for 12 hours. The product obtained was shown to be (438) and an intermediate such as (437) could also be involved in this cycloaddition (74JOC3763). In contrast, thiobenzoyl isocyanate added in a [4-1-2] fashion, and after ring expansion gave a thiadiazepine derivative. 

The AfA/ -diacetylphenylhydrazine derivatives 2 are converted into 5,6-diacetyl-5,6-dihy-drodibenzo[ft,/][l,4,5]thiadiazepines 3 in the presence of potassium carbonate. (The reaction fails in the absence of the chlorine substituents.) Hydrolysis of the products 3 results in the tricyclic hydrazines 4, which are transformed quantitatively into dibenzothiadiazepines 5 in... 

Dibenzo[6,/][l,4,5]thiadiazepine is converted into the 5,6-dihydro derivative on treatment with hydrazine in the presence of 5% palladium on charcoal.153... 

When heated, the benzotrithiadiazepines undergo a rearrangement with loss of nitrogen to give 1,2,3-benzotrithioles, e.g. the reaction of 6,9-dimethyl-7,8-diphenyl-1,3A4,5,2,4-benzotri-thiadiazepine.393... 

Die Elektrolyse von 2,2 -Dinitro-diphenylsulfid an Quecksilber fuhrt in saurem Milieu zum Diamin, sonst zum Dibenzo-1,4,5-thiadiazepin, das zum 9,10-Dihydro-Derivat (Klemmenspannung 40-65 V) weiter reduziert werden kann5 ... 

Keywords Thiadiazines Thiadiazepines Thiazepines Thiazines Thiazoles Thiophenes... 

Potent antimicrobial l,2,4-triazolo[3,4-fc]-l,3,4-thiadiazepines derivatives were prepared from readily accessible substituted 2-mercapto-l-aminotria-zoles and substituted chalcones on basic alumina in a solvent-free microwave-assisted synthesis (Scheme 28). Exposure of the reaction mixtures to microwaves led to an important decrease of the reaction time, which has been brought down from hours to seconds, accompanied by improved yields as compared with conventional heating [36]. This facile, rapid, and economic... 

Other types of HIV-1 protease inhibitors have also been prepared using microwave-promoted Suzuki reaction [37]. The symmetric cyclic sulfamide (3K,4S,5S,6it)-3,6-bis(phenoxymethyl)-2,7-bis[4-(2-thienyl)benzyl]-l,2,7-thi-adiazepane-4,5-diol 1,1-dioxide, for instance, was synthesized via cross-couphng of (3aS,4R,8it,8aS) - 5,7 - bis(4 - bromobenzyl) - 2,2 - dimethyl - 4,8 - bis-(phenoxymethyl) hexahydro [1,3] dioxolo [4,5 - d] [ 1,2,7 ] - thiadiazepine 6,6 - dioxide with 2-thienylboronic acid for 3 min at 45 W (Scheme 19). 

An expeditious route to the cyclic sulfamide HIV-1 protease inhibitors of type 145 and 146 (tetrahydro-l,2,7-thiadiazepine 1,1-dioxide derivatives) from 141 and 142 hinges on palladium-catalysed amidation reactions. These reactions of 144 and 143 were microwave promoted and provided, after removal of the cyclic ketal protecting group, moderate to good yields of (145, 57%) and (146, 66%) for example with R = NHCOCH2-2-naphthyl <06T4671>. 

The new heterocyclic system represented by compounds of type 147 (eg. R = Cl), and containing a bis-fused [l,3,4]thiadiazepine moiety, was prepared by cyclocondensation of 1-aminobenzimidazoIe-2-thione with 6-chloropyrimidine-5-carboxaldehydes. Some representatives of the system (e.g. 147, R = NMe2> showed anti-HIV activity <00SC3719>. 

Diethyl sodiomalonate, prepared from diethyl malonate and sodium hydride, was reacted with isothiocyanate (528) in DMF by dropwise addition at 5°C. The reaction mixture was then stirred at ambient temperature for 1 hr to give (l,3,5-thiadiazepin-2-ylidene)malonate (529) in 76% yield (86S817). 

Syntheses of this class of compounds usually involve 1,2,5-thiadiazepine ring 333 (Figure 6) which is stable in the S-oxidized form and structurally represents cyclic pyrrole N-sulfonyl derivatives. Most of the synthetic strategies include formation of an S-Npyrroie bond in the early stages. A final cyclization step typically includes (i) intramolecular cyclization by creation of an N-X bond from a suitable pyrrole precursor or (ii) a 6 + 1 type cyclization that involves dielectrophilic species to form linker X and utilizes the nucleophilicity of the phenyl amino group and of the pyrrole ring at C2. Intramolecular processes with the formation... 

Fusion of the imidazole ring to pyrrolo-benzothiadiazepine 340 can be achieved by straightforward TosMIC cycloaddition approach (Scheme 72, Section 4.2 (1994JHC1033)). An alternative sequence starts with the addition of nitromethane to the C-N double bond on the thiadiazepine ring, nitro group reduction and manganese oxide oxidation of the intermediate dihydroimidazole derived from amine 342 and tiiethyl ortho formate. 

Diester 352 (Scheme 74, Section 4.2 (1994SC2685)) after the sulfur atom oxidation undergoes hydrolysis and intramolecular acylation to the pyrrolo-thiadiazepine 353 with a fused lactam ring. 

Structurally similar seven-membered dihydro-l,2,7-thiadiazepine 69 and l,2,7-thiadiazepan-3,6-dione 70 were obtained by an unexpected dimerization of acetoxime 71 (1997BSB605) and a ring closure of dicarboxamide 72 (1995CC1449). Curiously, the reaction of sulfur monochloride containing two sulfur atoms in both cases led to the insertion of one sulfur atom to the seven-membered ling or three sulfur atoms to the by-product 73 in the second reaction, but not two sulfurs (Scheme 36). 

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