Sulfur heterocycles five-membered

Two types of sulfur-containing five-membered heterocycles are convenient precursors of thiocarbonyl ylides, namely, 2,5-dihydro-1,3,4-thiadiazoles (20) and l,3-oxathiolan-5-ones (21) (Scheme 5.5). The precursors 20 are accessible by two different methods. 

Reaction kinetics for the interaction of 5-alkyliminothiatriazoles 52 or 58 with heterocumulenes, nitriles, ketones, imines, or other dipolarophiles a=b show that the decomposition of the thiatriazole is bimolecular, and new heterocyclic five-membered rings 71 are formed (Scheme 15). The term masked 1,3-dipolar cycloaddition was used by L abbe and co-workers for this type of reaction <1978JOC4951>, the thioimidate function being the masked 1,3-dipole. The reaction is thought to involve a thiapentalenic intermediate 70 with hypervalent sulfur. The product 71 is itself a masked dipole and often further reactions take place. 

Imidazole is a heterocyclic five-membered ring containing nitrogen atoms. Various imidazole derivatives are found to possess biological activities. Biotin is of interest here, it is a heterocychc sulfur-containing B-complex vitamin with imidazole and thiophene rings fused along the C - C bond. Biotin serves as a carrier of CO2 in carboxylation reactions. Biotin-enzyme reacts with CO2 in the presence of ATP to form a carboxybiotin-enzyme complex. This complex hands over the CO2 to pyruvate to produce oxaloacetate [139]. 

As part of our current interest in SPOS, we examined the efficient and rapid synthesis of nitrogen- or sulfur-containing five-membered ring heterocycles and their fused counterparts by solid-phase strategies using Merrifield resin 1 and carbon disulfide (Figure 10.1). In this chapter, we review the synthesis of these five-membered ring heterocycles and their fused counterparts on solid support with carbon disulfide and Merrifield resin 1 as a solid support. 

The strain energies of these five-membered heterocycles are relatively small with values of 23.5, 24.8 and S.SkJmoF estimated for tetrahydrofuran, pyrrolidine and tetrahy-drothiophene respectively (74PMH(6)199). The closeness of the values for the two former compounds reflects the almost identical covalent radii of oxygen (0.66 A) and nitrogen (0.70 A) atoms. The sulfur atom with a much larger covalent radius of 1.04 A causes a... 

In Table 29 the u(C=0) and other characteristic bands are given for some saturated five-membered heterocycles, and compared with the corresponding absorption frequencies for cyclopentanone. Adjacent NH groups and sulfur atoms have the expected bathochromic effect on r (C=0), whereas an adjacent oxygen atom acts in the reverse direction. The CHa vibrations of cyclopentanone are repeated to a considerable extent in the heterocyclic analogs. 

Phenylthiazirine (40) can be isolated as an intermediate in the photolysis of 5-phenyl-1,2,3,4-thiatriazole and also from other five-membered ring heterocycles capable of losing stable fragments see Scheme 2 (81AHC(28)231). Photolysis of 5-phenylthiatriazole in the presence of cyclohexene yields cyclohexene episulfide (60CB2353) by trapping the sulfur atom. 

Any heterocycle containing the OCH=CH moiety can in principle extrude the superfluous fragment and form oxirene, as illustrated for a five-membered ring in Scheme 105. Probably the most propitious AB fragment would be nitrogen, but the required 1,2,3-oxadiazole (123) is unknown (see Chapter 4.21), probably because of ready valence tautomerization to diazoethanal (Scheme 106) (this approach has been spectacularly successful with the sulfur analogue of (2) (8UA486)). The use of (123) as an oxirene precursor is thus closely linked to the important diazo ketone decompositions discussed in Section 5.05.6.3.4(f). 

The molecular and crystal stmctures of 2-phenylbenzotellurazole were determined by X-ray (89KGS1690). The dihedral angle between the planes of the five-membered heterocycle and 2-phenyl ring is 31.2°. In contrast to benzoisotel-lurazole, no shortened intermolecular Te- N contacts were found in the crystal stmcture of 2-phenylbenzotellurazole. Consequently, no anomalies in solubility and melting point were revealed for this compound as compared with its sulfur and selenium congeners. 

With X = RN the C-1 electrophilic center is most active, and five-membered heterocycles 131 are generated (69ZOR1179). With X = O there is a competition between C-1 and C-3 electrophilic centers, the role of the latter increasing on going to sulfur analogs (X = S) in accord with a decrease in the - -M effect in this series (81UK1252). 

Huisgen has reported in 1963 about a systematic treatment of the 1,3-dipolar cycloaddition reaction as a general principle for the construction of five-membered heterocycles. This reaction is the addition of a 1,3-dipolar species 1 to a multiple bond, e. g. a double bond 2 the resulting product is a heterocyclic compound 3. The 1,3-dipolar species can consist of carbon, nitrogen and oxygen atoms (seldom sulfur) in various combinations, and has four non-dienic r-electrons. The 1,3-dipolar cycloaddition is thus An +2n cycloaddition reaction, as is the Diels-Alder reaction. 

Thiamin, or vitamin Blf contains a positively charged five-membered nitrogen-sulfur heterocycle called a thiazoliwn ring. Explain why thethiazolium ring is aromatic. 

The diazotization of heteroaromatic amines is basically analogous to that of aromatic amines. Among the five-membered systems the amino-azoles (pyrroles, diazoles, triazoles, tetrazoles, oxazoles, isooxazoles, thia-, selena-, and dithiazoles) have all been diazotized. In general, diazotization in dilute mineral acid is possible, but diazotization in concentrated sulfuric acid (nitrosylsulfuric acid, see Sec. 2.2) or in organic solvents using an ester of nitrous acid (ethyl or isopentyl nitrite) is often preferable. Amino derivatives of aromatic heterocycles without ring nitrogen (furan and thiophene) can also be diazotized. 

Five-membered sulfur-containing heterocycles are important synthetic intermediates and have found a variety of applications in medical, agricultural, and material chemistry. Looking for potential candidates for ferroelectric display applications. Seed s group investigated the preparation of liquid crystals... 

As with five-membered heterocycles, phosphorus pentasulfide may replace a ring oxygen atom by sulfur, or it may effect replacement in an acyclic precursor and then bring about cyclization. Thus isochroman-l-one (99) is converted into thioisochroman-l-thione (100) under the same conditions a 3-arylisocoumarin( 101) produces a 3-ary 1-1-thioisocoumarin (102) only, with no replacement of the ring oxygen atom.122 A typical example of thiation, followed by cyclization, is the formation of 2-alkyl- or 2-aryl-3,l-benzo-thiazine-4-thiones (103) from /V-acylanthranilic acid esters (104) by treatment with phosphorus pentasulfide in boiling xylene.122... 

The preparation of five-membered rings in solid-phase organic chemistry has been reported in several publications. Versatile syntheses of these heterocycles with different numbers and kinds of heteroatoms have been described. The synthesis of five-membered rings containing one nitrogen atom (Fig. 3.6) as pyrrolidines (231) [311-316] pyrroles (232) [317-320] pyrrolidinones (233) [321-323] pyr-rolinones (234) [324—326] 2,5-pyrrolidinediones (235) [327-329] 2,4-pyrrolidine-diones (236) [330-332] 2,5-pyrrolinediones (237) [333] or heterocycles with one oxygen or one sulfur atom like tetrahydrofurans (238) [334—336] 2,5-dihydrofurans (239) [337], furans (240) [338, 339], yS-lactones (241) [340-343], 2,5-dihydrofura-nones (242) [344] (Scheme 3.35) and thiophenes (243) [345, 346] can be accomplished on solid supports. 

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