Heterocycles with Two Heteroatoms

Thiaisatoic anhydrides have been considered as precursors for the synthesis of tricyclic compounds containing thiophene ring. Syntheses of these anhydrides have a major problem owing to the instability of their precursors thiophene o-aminoacids, which easily decarboxylate at room temperature. Under MWI, alkaline hydrolysis of 

Imidazolo[2,3-Z)]thiazine 458 and triazolo[3,4-Z)]thiazine 460 were prepared in 80-85% yields by base-catalyzed reaction of imidazole 456 or triazole 459 with 

Several methyl aryl ketones reacted with sulfur and morpholine (469) under sol-vent-free conditions in a domestic MW oven for 3.5 6 min to give thiomorpholides 

Although some solution-phase Ugi reactions were known to proceed rapidly, reaction times from 24 h to several days have been usually required for the solid phase. However, MWI-assisted solid-phase Ugi condensations of 2-morpholinoethyl isocyanide 475, aldehydes, and carboxylic acids in a mixture of dichloromethane and methanol (2 1) on amino-functionalized TentaGel S Ram as support gave 

MW played an important role in producing regioselective isomers from Suzuki coupling of 4,5-dichloropyridazinone (505) with phenylboronic acid in the presence of Pd catalyst. An extensive MW-assisted screen led to the identification of Pd(PEt3)Cl2 as an ideal catalyst with superior rate and selectivity. Thus, a mixture of 505 and phenylboronic acid in aqueous acetonitrile was heated under MW for 10 min in the presence of Na2C03 and Pd(PEt3)Cl2. The catalyst offered excellent selectivity for 505, whereby 100% conversion occurred to give pyridazinones 506, 507, and 508 

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Heterocycles with two heteroatoms present no special problems and there are often seyeral ways to do the first disconnection. One guide is to look for a small recognisable fragment containing the two heteroatoms. Try this one ... 

Six-membered heterocycles with two heteroatoms are prepared by reaction of diketene with a substrate containing a C—O or C—N multiple bond. With carbonyl compounds diketene reacts in the presence of acids to give l,3-dioxin-4-ones. The best known is 2,2,6-trimethyl-4H-l,3-dioxin-4-one [5394-63-8] (15), the so-called diketene—acetone adduct, often used as a diketene replacement that is safer to handle and to transport, albeit somewhat less reactive than diketene itself (103,104), forming acetylketene upon heating. 

The tricyclic compounds 35 are among the most studied six-member Te-containing heterocycles with two heteroatoms in the ring. The first representive... 

The fusion of four membered-heterocycles with two heteroatoms onto face a of the quinoline offers two isomeric combinations of the tricyclic ring system l,2-heterocyclo[2,3-a]quinoline and l,3-heterocyclo[3,2-a]quinoline. The later one of these two ring systems is the only one that examples of it namely, l,3-thiazeto[3,2-a]quinoline have been reported. Moreover, examples of those fused on faces ij or j are not known (Fig. 3). 

Considering the formation of saturated five-membered heterocycles with two heteroatoms, it is worth to note the possibility to prepare 1,3-dioxolanes, dithiane, oxathianes 148 [93] and dioxolanones 149 [94] by condensation of the corresponding carbonyl compounds under microwave irradiation in acid medium (Scheme 52). The reaction, which is very useful for the protection of carbonyl compounds or for the preparation of useful synthetic intermediates, has also been carried out under batch conditions over Montmorillonite KIO clay in more than 150 g scale, using a 1 L quartz reactor [95]. 

Table 1 Linearly fused (5 5 5) heterocycles with two heteroatoms...

Five-membered heterocycles with two heteroatoms have the jr-electron deficiency of Y-type heteroatoms compensated by the jr-electron excessive character of the X-type atoms therefore, this category includes some of the most stable heterocycles. For example, NMR spectral data and chemical behavior (e.g., resistance to oxidation by potassium permanganate) suggest that pyrazole and imidazole have delocaliza-... 

Fig. 3.7 Five-membered heterocycles with two heteroatoms obtained by sol-id-phase chemistry.

We have looked at the five-membered aromatic heterocycles pyrrole, furan and thiophene in Section 11.5. Introduction of a second heteroatom creates azoles. This name immediately suggests that nitrogen is one of the heteroatoms. As soon as we consider valencies, we discover that in order to draw a five-membered aromatic heterocycle with two heteroatoms, it must contain nitrogen A neutral oxygen or sulfm atom can have only two bonds, and we cannot, therefore, have more than one of these atoms in any aromatic heterocycle. On the other hand, there is potential for having as many nitrogens as we like in an aromatic ring. 

Oximes and their derivatives are widely used in organic synthesis. A number of reviews are devoted to the chemistry and biological activity of oximes and their derivatives The synthesis, reactions and biological activity of oximes containing a heterocyclic substituent, e.g. furan and thiophene", indole and isatin, pyridine, pyrrole, quinoline and five-membered heterocycles with two heteroatoms have been reviewed. 

Five-membered heterocycles with two heteroatoms connected in 2-position also form two step redox systems of the Weitz type which may be described as hetero-tetrasubstituted ethylenes on the level of RED . The great significance of tetrathia (selena) flilvalenes 17 as a basis for organic metals has already been discussed ... 

STRUCTURE OF FOUR-MEMBERED HETEROCYCLES WITH TWO HETEROATOMS... 

This method is by far the most successful and most widely used in the synthesis of four-membered heterocycles with two heteroatoms. In principle these formal additions can be envisioned to occur by (a) two displacements, (b) thermal concerted [2 + 2] cycloadditions, (c) photoinduced [2 + 2] additions, (d) stepwise zwitterionic intermediates or dipolar reactants, and (e) radical intermediates. In some cases the mechanisms have been elucidated but in many others the actual mode of addition is not known. For this reason, no attempt has been made to formally divide the latter four (b-e) into categories and only the first [(a), two displacement reactions] is covered separately. 

Intramolecular Interactions in Saturated Heterocycles with Two Heteroatoms I. A. Shlygina and V. Z. Gabdrakipov, Tr. Inst. Khim. Nauk, Akad. Nauk, Kaz. SSR, 1980,53,55-75. 

Thus far only eight different types of five-membered heterocycles with two heteroatoms, one of these being tellurium, are known. Of special interest are those containing S,Se, or Te as the second heteroatom in the ring. Such compounds afford electron-donor components of charge-transfer complexes or radical cation salts, exhibiting properties of the so-called organic metals. 

Tellurium-Containing Heterocycles with Two Heteroatoms Igor D. Sadekov and Vladimir I. Minkin... 

Two chapters deal with the increasing influence in heterocyclic chemistry of unusual heteroatoms. Igor D. Sadekov and Vladimir I. Minkin of Rostov University (Russia) survey the chemistry of tellurium-containing heterocycles with two heteroatoms, while Allan Blackman of the University of Otago (New Zealand) summarizes the influence of metals on the reactivity of heterocyclic ligands in his chapter, Reactions of Coordinated Ligands. ... 

Sadekov, I. D., Minkin, V. I., Tellurium-containing Heterocycles with Two Heteroatoms, 58, 47. 

Dications, derivatives of Se- and Te-heterocycles with two heteroatoms 91YGK636. 

From five-membered ring heterocycles with two heteroatoms 938... 

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