New heterocyclic ring system

In order to study heterocyclic steroid analogues, such as the 7,11-dithiaazasteroid analogues, Fravolini developed the synthesis of new heterocyclic ring systems tri- and tetracyclic 2,1-benzothiazines <82JHC1045>. Intermediate 137 was prepared from 1-methyl-4-oxo-lH-2, -bcnzothiazinc-4(3f/)-onc 2,2-dioxide 37 and thioglycolic acid and could be converted into 6-methyl-4-oxo-3,4-dihydro-2//,6//-thiopyrano[3,2-c][2,l]benzothiazine 5,5-dioxide 138 by cyclization with polyphosphoric acid. The reaction of 138 with dimethyl... 

Thiadiazolines are less stable compared to 1,2,4-thiadiazoles and this can be attributed to the loss of aromatic character. They are readily cleaved at the N-S bond under fairly mild conditions (H2S in pyridine) in some cases, the product from ring cleavage can recyclize to give new heterocyclic ring systems. The 3-imino-l,2,3-thiadiazoline 24 when reduced with H2S affords the two J-triazine derivatives 25 and 26 (Scheme 3) <1996CHEC-II(4)307>. 

A derivative of the new heterocyclic ring system 4-benzyl-3-(2,6-dichlorophenyl)-6-ethoxy-4,5-dihydro-l,2,4,6-oxadiazaphosphinine 6-oxide (382) is prepared by the reaction of sterically hindered hydroximoyl chloride 381 with aminomethylphosphonate (equation... 

New Heterocyclic Ring Systems Predicted by Computer-AssIsted Organic Synthesis (CAOS). A computer program written for this purpose (55,56) can be used to predict the formation of additional heterocyclic systems from the reactants mentioned in the above sections. These are the systems which, of course, have not been experimentally detected as reaction products so far. 

A new heterocyclic ring system, 5//-pyrazolo[3,4- /]-l, 2,3-thiadiazoles (41), results from a one-pot, two-step reaction of the pyrazolodithiazolium chlorides (29). Sequential treatment of the derivatives (29) with base, sodium dithionite, and sodium nitrite followed by acidification afforded (41) (Scheme 3). For substrates (29a,b) potassium hydroxide was chosen, whilst for (29c,d) sodium bicarbonate was found to be superior. In the latter cases, potassium hydroxide caused appreciable hydrolysis of the ester substituent. A further point of interest is the significant quantity of disulfide (43) which can form on reaction of 6-carboethoxy-5-methylpyrazolodithiazolium chloride (29c). This, however, need not represent a problem since compound (43) can be converted in situ or isolated and converted to the desired product (41c) in good yield (Scheme 4) <84JOCl224>. 

Cyclisation of 5-benzylsulfonyl-3-chloro-4-methoxycarbonylaminoisothiazole (18) using an excess of NaOMe in DMF gave 3-methoxy-5-oxo-6-phenyl-5,6-dihydro-4//-isothiazolo[5,4-f>]-1,4-thiazine 7,7-dioxide 19, which was the first representative of a new heterocyclic ring system. Compound 18 was prepared in good yield (81%) by the reaction of 17 with PhI(OAc)2 in methanol <02RCB187>. 

A new heterocyclic ring system, 5/-/,12/-/-[1]Benzoxepino[4,3-b]indol-6-one, was prepared by the Fischer indole cyciization of a substituted benzoxepin-5b-one phenylhydrazone by G. Primofiore and co-workers. The phenylhydrazone precursor was prepared via the Japp-Klingemann reaction of the corresponding 3,4-dihydro-4-hydroxymethylene[1]benzoxepin-5(2H)-one. 

Chetoni, F., Da Settimo, F., Marini, A. M., Primofiore, G. Synthesis of some 5H,12H-[1]benzoxepino[4,3-b]indol-6-ones. A new heterocyclic ring system. J. Heterocycl. Chem. 1993, 30,1481-1484. 

Scheme 10 shows the preparation of the first isolable example of a new heterocyclic ring-system, namely the 3-silaoxetan (61). ... 

A new heterocyclic ring system, pyrrolo(3,2-3,4]-l,8-naphthyridine (IX-121) is obtained from the cyclization of mono- and diW-acyl derivatives of 2-aminonicotyrine (IX-120) with phosphoms oxychloride. Thus, 2-dibenzoyl-aminonicotyrine is dissolved in toluene and phosphorus oxychloride and heated... 

The reactivity of 1,3-oxazinium salts is comparable to that of pyryhum salts. Nucleophiles are added at C-6 and, after ring-opening and recycHzation, incorporated into the new heterocyclic ring system. Thus, 1,3-thiazinium salts 31 are obtained with H2S and subsequent treatment with HCIO4 ... 

The structure and stereochemistry of chuangxinmycin (11a), a new antibiotic isolated from the micro-organism Actinoplanes tsinanensis, collected from a soil sample in Shantung Province, China, have been confirmed by synthesis (Scheme l).12a Chuangxinmycin contains a novel heterocyclic ring system, and is claimed to be effective in the treatment of septicaemia and urinary and biliary infections. 

Interest in (5,5)-fused ring systems developed in separate, albeit closely related, directions. In the first, chemists continue their quest for new compounds having unique biological, chemical and physical properties. In the second, emphasis is on the classification of aromaticity based upon molecular conformity with Hiickel s rule. An increasing understanding of the fundamental chemistry of heterocyclic ring systems has led to considerable advances in this field, as evidenced by the growing list of applications as biocides and in industrial processes. 

The new pyrazolo[l,5-tf][l,3,5]benzoxadiazocine heterocyclic ring system 123 was prepared by cyclization of 4,5-dihydro-3-methyl-5-(2-hydroxyphenyl)-17/-pyrazole-l-carboximidamide with triethyl orthoformate. A reaction mechanism involving re-esterification of triethyl orthoformate with phenolic hydroxyl of the additional equivalent of hydroxyphenyl pyrazoline was proposed to explain the formation of the product with an additional guanidine moiety (Equation 17 <2002J(P1)1260>). 

The hetero-Diels-Alder reaction is amongst the most efficient processes for the synthesis of six-membered heterocyclic ring systems. Solvent-free conditions have been used to improve reactions of heterodienophiles and heterodynes with low reactivities. Cado et al. (1997) have described the hetero-Diels-Alder reaction of ethyl lH-perimidine-2-acetate as heterocyclic ketene aminal with ethyl propiolate nnder solvent-free conditions with focused microwave irradiation. The new fused perimi-dines (23) were obtained in good yields (67-98%). 

Most bryozoan secondary metabolites are alkaloids and the large majority of them have novel structures. Heterocyclic ring systems which are represented include pyrrole, pyridine, indole, isoquinoline, purine and p-carbollne as well as numerous new polycyclic systems. 

In Neunhoeffer s contribution to CHEC-I a detailed and very competent discussion is found of the synthesis of the tetrazine system <84CHEC-I(3)531>. All principal synthetic ways are described there, and no new method has been published in the meantime, especially for the fully conjugated system. Therefore the discussion in this contribution is limited to Scheme 57, which summarizes the most successful ways to the heterocyclic ring system via the dihydro compounds. 

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