New heterocyclic ring

These consider ring syntheses from non-heterocyclic compounds first, followed by transformation of other heterocyclics. Syntheses in which no new heterocyclic ring is formed are dealt with primarily in the appropriate reactivity section, but with cross-referencing when necessary. Ring syntheses from acyclic precursors are dealt with as logically as possible according to the number and nature of the new ring bonds formed in the process. 

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... 

This Chapter will discuss the formation of heterocycles that contain nitrogen and that involve atoms of the original sugar, and not the combination of existing heterocycles with saccharide derivatives. Thus, for example, the synthesis of nucleosides will not be included, but the formation of anhydronucleosides, in which a new heterocyclic ring has been introduced into the molecule, will be treated. 

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. 

Treatment of the hydrazine 283 with acetylacetone yields the corresponding -substituted 3,5-dimethylpyrazole (284) incorporation of the hydrazino group into this new heterocyclic ring has a striking stabilizing effect on the 1,2,4-thiadiazole ring of the resulting compound.140... 

Synthesis of Heterocyclic Compounds , A. L. Mndzhoian, Plenum, New York, 1959-1961. Simple Synthesis and Chemical Behavior of New Heterocyclic Rings F. Asinger and M. Thiel, Angew. Chem., 1958, 70, 667-683. 

Intramolecular oxirane-ring opening at C-4 substituted anhydride 148, where Nu = -0 (CH2CH2) OH or -O (CH2)raNH2, affords a new heterocyclic ring fused to 1,6-anhydro-jS-D-hexopyranose.443... 

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>. 

Heterocyclic syntheses so far considered have involved the imino ether function only, with the new heterocyclic rings being produced by displacement of the ether group followed by cyclization to the... 

Alkylation of purines, in particular adenine and guanine, with bifunctional reagents may result in a new heterocyclic ring being fused to the purine. 

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. 

Functional groups or side chains of pyridazines have been used in the formation of new heterocyclic rings. Hydrazinopyridazines, when condensed with 1,3-dicarbonyl compounds give JV-pyridazinylpyrazoles. Azido-pyridazines and acetylenes give triazolylpyridazines on which various re-... 

The allyl silane 126 is coupled with the imide 127 by a Mitsunobu procedure and one of the carbonyl groups is reduced to give the alcohol 129. Treatment with CF3C02H now cyclises the allyl silane to give a new heterocyclic ring 130. 

The diene alcohol derivative 68 is used to prepare the starting material 69 for an intramolecular hetero-Diels-Alder reaction to give a new heterocyclic ring 70 that can be cleaved with phenyl Grignard to release a sulfoxide 71 for the preparation of a new allylic alcohol 72. Notice that the stereochemistry of the sulfoxide is shown and that there is complete control over 2D and 3D stereochemistry. The allylic alcohol 72 was used in Weinreb s synthesis of toxins10 produced by fresh water blue-green algae. 

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 ... 

Exo- or endo-cycloheteropalladation of double or triple, Pd(II)-coordinated carbon-carbon bond followed by CO insertion and displacement by nucleophiles ends with the elimination of Pd(0) and delivering of a new heterocyclic ring. Reactions involving an e%o-cyclization route are most frequently observed. 

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