Ring closure direct

An interesting application is the preparation of 1 2 3 4-tetrahydrocarb azole (VI), which is formed when phenylhydrazine is added to a boiling aolutiai of cyclohexanone in acetic acid the plienylhydrazone (V) Intermediately produced undergoes ring closure directly ... 

Ring closure direction can be controlled by employing different halogen substituents in both phenol sites [160]. For example, in the case where one phenol is flanked by two bromine atoms and the other by two chlorine atoms, bromine will be replaced by oxygen. 

Likewise benzo-annelated fluoranthenes, (128), (130), and (132), are obtained by thermolysis of the corresponding enamino derivatives of benzofluorenes (127), (129), and (131). Whereas one direction of cyclization is open for (127), there exist two possibilities of ring-closure direction for (129) and (131), but only the one was realized which we expected in correlation to the calculated lower localization energies (see Fig. 1, XI., Section II., C.) ... 

A two-step route in 67% overall yield again utilized 3-lithiothiophene, this time in reaction with l,2-bis(2,2-diethoxyethyl)disulfide (20), producing the acetal 21, electrophilic ring closure directly to 1 resulting from mild acid (Amberlyst 15) treatment (Scheme 4) [24]. 

Thiazolium salts can be obtained either directly by slight modifications of ring-closure methods, already described for the parent bases, or by classical quaternization of the bases, the detailed mechanism of which have been reported in Chapter III the quaternization is best represented by a classical SNj mechanism, the solvent playing an important part (14) unless the reaction is run without any solvent. 

With R] different from R2 two isomeric compounds (138 and 139) are possible, depending on the direction of ring closure (86). However, only one form is generally obtained. Finally, the trisubstituted thioureas such as N,N,N -trimethylthiourea react with chloroacetone to give a thiazolium salt, in a reaction identical to that of the N-monosubstituted thioamides (Scheme 67). 

Chelation itself is sometimes useful in directing the course of synthesis. This is called the template effect (37). The presence of a suitable metal ion facihtates the preparation of the crown ethers, porphyrins, and similar heteroatom macrocycHc compounds. Coordination of the heteroatoms about the metal orients the end groups of the reactants for ring closure. The product is the chelate from which the metal may be removed by a suitable method. In other catalytic effects, reactive centers may be brought into close proximity, charge or bond strain effects may be created, or electron transfers may be made possible. 

The direction of ring closure can often be influenced by the nature of the dehydrogenation agent. The substituted thiosemicarbazone (223) with AI2O3 in chloroform formed the... 

The dimethylsulfonium ylide (568) added readily to aroyl isocyanates to give the intermediate addition product (569). This on heating underwent ring closure with loss of dimethyl sulfide to form the 4-hydroxyoxazole (570) (73T1983). This normal C-acylation of the sulfonium ylide also leads to thiazoles with thiobenzoyl isocyanate in this case the initial acylation product was not isolated, the thiazole being obtained directly. 

Figure 4.9 Mechanisms of the reactions catalyzed by the enzymes mandelate racemase (a) and muconate lactonizing enzyme (b). The two overall reactions are quite different a change of configuration of a carbon atom for mandelate racemase versus ring closure for the lactonizing enzyme. However, one crucial step (red) in the two reactions is the same addition of a proton (blue) to an intermediate of the substrate (red) from a lysine residue of the enzyme (E) or. In the reverse direction, formation of an intermediate by proton abstraction from the carbon atom adjacent to the carboxylate group.

HOMO of cw-1,3,5-hexatriene anticipates the preferred direction of ring closure. 

The ring closure of a diene to a cyclobutene can occur with rotation of the two termini in the same conrotatory) or opposite disrotatory) directions. For suitable substituted compounds, these two reaction modes lead to products with different stereochemistry. 

This problem has been circumvented by utilizing the ipso-directing capability of a silicon substituent at the 2 position of the D ring to facilitate ring closure at this position. Benzylisoquinoline 26 condensed with formaldehyde to give predominantly product 28 when R = H. However, when R = SiMea, 27 was the only product observed and was isolated in excellent yield.Several members of the protoberberine family of natural products have been synthesized using this strategy. 

Most N-phenyl quaternary salts are not prepared by direct quater-nization but rather by introducing the nitrogen substituent before ring closure. It has recently been found that diphenyl iodonium boro-fluoride reacts smoothly with pyridine the phenyl carbonium ions formed give the 1-phenylpyridinium ion good yield. ... 

A second direct route to an extended 3,4-dihydro-j8-carbolinium system (120) using the Bischler-Napieralski ring closure is based on the cyclization of intermediates of general structure 118. Three approaches to intermediates of this type have been developed in connection with stereospecific syntheses in the indole alkaloid field. The first approach, introduced independently by Stork and Hill and by van Tamelen and co-workers and often used... 

The hetero ring in 4-(l -hydroxyalkylidene)-5-oxazolones is cleaved by alcoholic HCl to form alkyl a-acylaminoacylacetates, which cyclize to oxazole-4-carboxylates [Eq. (25)]. This rearrangement occurs directly in alkali, and a carbon-14 tracer study has substantiated a mechanism involving ring opening followed by the alternative ring closure. ... 

A more recent derivative with activities typical of the class is nitrazepam (21). Reaction of 2-amino-5-nitrobenzophe-none (19) with bromoacetylbromide affords the amide, 20. Ring closure in liquid ammonia gives nitrazepam (21). More simply, diazepinone, 22, can be nitrated directly at the more reactive C7 position with potassium nitrate in sulfuric acid. 

The direct aziridinadon of nitroalkanes has been repotted for the first dme. Treatment of nitroalkene with an excess of CaO and NsONHCO-.Et fNs =4-nitroben2enesulfonyl gives the ct-nitroaziridine in good yields fEq. 10.70. ° The reaction proceeds via aza-Michael reaction followed by a ring closure. 

Conrotatory (Section 30.2) A term used to indicate that p orbitals must rotate in the same direction during electro-cyclic ring-opening or ring closure. 

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