Other Heterocyclic Systems

Other heterocyclic systems prepared by a thionyl chloride reaction include fused thiazoles,71 thiatriazoles,72 oxathiins,73 and dithiins 74 some further examples are given in reviews.53 

The chemistry and reactions of /V-sulfinyl compounds have been summarized in two reviews appearing in the late 1960s and early 1970s.75 There is also a short article in a recent comprehensive text.76 

Kresze, in Organosulfur Chemistry (M. J. Janssen, ed.), p. 259. Wiley (Interscience), New York, 1975 H. W. Roesky, in Sulfur in Organic and Inorganic Chemistry (A. Senning, ed.), Vol. 1, Chapter 9. Dekker, New York, 1971. 

Action of the appropriate alkyl bromide on N-cyanourethane 130 affords the N-alkyl cyanourethanes 131 that, under the action of the hydroxylamine, through the intermediate formation of unstable hydroxyguanidines 132, yield the final products 133. These products have been found to display antithrombotic properties after 

In an in vivo thrombosis model, these products displayed antithrombotic effects that were generally lower than those of the corresponding azoamidoximes. This is probably due to a rather slow cleavage of the prodrugs 136 to the drugs 134. The most potent oxadiazol-5-one proved to be the phenyl derivative (136, Ar=QH5). 

All products showed antithrombotic activity the most potent was found to be the dimethyl derivative, which also significantly decreased blood pressure when administered orally to spontaneously hypertensive rats. Possible involvement of NO in this action was suggested but not demonstrated. 

1 Feelisch, M., Stamler, J. S. (eds.) Methods in Nitric Oxide Research, John Wiley, Chichester 1996 

8 Friedrichsen, W., Methoden der organischen Chemie/ (Houben-Weyl) Bd. E8c. Hetarene.-3. Stuttgart New York Thieme. Teil 3 1994 p. 716 

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Other Heterocyclic Systems. Naphthalimides (15), where R = —NHCOR, are derivatives of 4-anTinonaphthalimide (69) and are used in plastics. The alkoxynaphthalimides (15, R = OCH ) (70,71) are of particular interest as fluorescent whitening agents. 

Despite considerable localization of tt-electrons at the nitrogen atoms of pyrimidine, the ring system is still sufficiently aromatic to possess substantial stability. This is a great advantage in the primary synthesis of pyrimidines, in the synthesis of pyrimidines from the breakdown or modification of other heterocyclic systems and in the myriad of metatheses required to synthesize specifically substituted pyrimidines. 

Benzisoxazoles undergo electrophilic substitution in the benzo ring, but with nucleophiles the reaction occurs in the isoxazole moiety, often leading to salicylonitriles with 3-unsubstituted systems. The isomeric 2,1-benzisoxazoles are characterized by the ease with which they may be converted into other heterocyclic systems. 

Formation from other heterocyclic systems 5.05.6.4 Conclusions... 

The formal derivation of the analogs, described in the foregoing, represents, from the point of view of systematic organic chemistry, a shift to the derivatives of other heterocyclic systems. In the case of pyrimidine aza analogs we arc dealing with derivatives of symmetrical or asymmetrical triazine in the case of purine aza analogs, the derivatives produced are those of imidazo[4,5]-i -triazine and z -triazolo [4,5-d] pyrimidine. 

Het = heteroaryl residue] follow second-order kinetics, first order with respect to each reactant. Regular kinetics of this kind are also observed in the reaction of sodium arylsulfide in methanol provided that no free thiol is present (see Section II,D, l,c). As to other heterocyclic systems, A -oxides and bromofuran derivatives show similar kinetic behavior. 

The diazotization of amino derivatives of six-membered heteroaromatic ring systems, particularly that of aminopyridines and aminopyridine oxides, was studied in detail by Kalatzis and coworkers. Diazotization of 3-aminopyridine and its derivatives is similar to that of aromatic amines because of the formation of rather stable diazonium ions. 2- and 4-aminopyridines were considered to resist diazotization or to form mainly the corresponding hydroxy compounds. However, Kalatzis (1967 a) showed that true diazotization of these compounds proceeds in a similar way to that of the aromatic amines in 0,5-4.0 m hydrochloric, sulfuric, or perchloric acid, by mixing the solutions with aqueous sodium nitrite at 0 °C. However, the rapidly formed diazonium ion is hydrolyzed very easily within a few minutes (hydroxy-de-diazonia-tion). The diazonium ion must be used immediately after formation, e. g., for a diazo coupling reaction, or must be stabilized as the diazoate by prompt neutralization (after 45 s) to pH 10-11 with sodium hydroxide-borax buffer. All isomeric aminopyridine-1-oxides can be diazotized in the usual way (Kalatzis and Mastrokalos, 1977). The diazotization of 5-aminopyrimidines results in a complex ring opening and conversion into other heterocyclic systems (see Nemeryuk et al., 1985). 

Conversion of other heterocyclic systems into pyridazines has also been used, for example the reaction of 3-aminopyrone 9 with hydrazine, followed by oxidative aromatisation <06T9718> and the more unusual utilisation of a 1,2,4-triazole 10 as the source of the N-N unit <06T8966>. In this latter transformation, the intermediate quaternary salt 11 was isolable. An even more unusual example was the reaction of the diazetidine 12 with enolates <06S2885>. 

In vivo, some other heterocyclic systems behave as NO-donors. Typical examples are the 3-amino-4-alkyl or arylalkyl derivatives of l,2,4-oxadiazol-5(4H)one 133 [169, 170]. These products can be synthesised following Scheme 6.25. 

Scheme 3.8 represents a typical ion-radical mechanism of the so-called vicarious nucleophilic substitution of hydrogen as it was described by the pioneering chemist M kocza (M kocza 1989) in his summarizing review. ESR studies of other heterocyclic systems in conditions of the hydrogen-to-nucleophile vicarious substitution were reported by the research group at the Siberian branch of the Russian Academy of Sciences (Donskaya et al. 2002, Vakul skaya et al. 2005, 2006, Titova et al. 2005). 

Examples of the Dimroth rearrangement (Section IV, F) include several s3mtheses of monocyclic triazoles from other heterocyclic systems (cf. Scheme 25). Triazole-5-thiols can be prepared by treatment of 5-amino-l,2,3-thiadiazoles with bases.A similar base-induced rearrangement of sydnoneimines provides a synthesis of 4-hydroxy-triazoles. ... 

From Other Heterocyclic Systems 4-Arylazoisoxazoles can rearrange to 2-aryltriazoles, and 4-amino-2//-triazoles can be prepared by reaction of 4-nitrosoimidazoles with hydrazines (Scheme 34). The hydrazones of 3-benzoyloxadiazoles are intermediates in the latter reaction.The generality of rearrangements of this type has been discussed, and a further example, involving the rearrangement of a 1,2,5-oxadiazole to a triazole, has been described. 

The basicity of some other heterocyclic systems will be considered in Chapter 11. 

Similar elimination of electron-rich aryl substituents was also described for other heterocyclic systems [76-78]. 

Halopyridines and other re-deficient nitrogen heterocycles are excellent reactants for nucleophilic aromatic substitution.112 Substitution reactions also occur readily for other heterocyclic systems, such as 2-haloquinolines and 1-haloisoquinolines, in which a potential leaving group is adjacent to a pyridine-type nitrogen. 4-Halopyridines and related heterocyclic compounds can also undergo substitution by nucleophilic addition-elimination but are somewhat less reactive. 

SYNTHESIS OF TRIAZOLES BY TRANSFORMATION OF OTHER HETEROCYCLIC SYSTEMS... 

Several other heterocyclic systems are accessible from monocyclic furoxans. In addition to providing a source of nitrile oxides and cycloadducts derived therefrom (Section 4.05.5.2.2), they... 

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