Iodine heterocycles five-membered

Figure 2.9 Known hypervalent iodine(lll) five-membered heterocyclic systems.

Within the broad field of hypervalent iodine chemistry, five-membered iodine(V) heterocycles occupy a special place. There has been significant interest in the cyclic X -iodanes, mainly 2-iodoxybenzoic acid (IBX)... 

Radical reactions of Hoffmann-Loffler-Freytag type with participation of iodine(III) compounds leading to five-member N-heterocycles 97YGK90. 

The five-membered hypervalent iodine heterocycles, benziodoxoles, are commonly used as convenient radical precursors [3,33]. The main advantage of benziodoxoles over the non-cyclic hypervalent iodine reagents is the higher thermal stability allowing the preparation of otherwise unstable derivatives with I-Br, I-OOR, I-N3, and I-CN bonds. The stable cyanobenziodoxoles 36-38 are prepared in one step by the reaction of cyanotrimethylsilane with the respective hydroxybenziodoxoles 35 (Scheme 16) [34, 35], or from acetoxybenziodoxole... 

A number of kinetic studies on the iodination of reactive five-membered heterocycles in buffered aqueous solutions have been reported. 

Relative rates and isomer distributions of the catalyzed acetylation of five-membered heterocycles are not affected by change in catalyst (tin tetrachloride or iodine).130 This is an indication that the electrophilic species involved in the reaction is the acetylium ion CH3CO+ rather than the oxonium complex. 

With five-membered heterocycles principal halogenation takes place alpha to the heteroatom (thiophene at C-238 indole is chlorinated at C-2,53 but iodinated at C-354). 

The intramolecular acylation of the vinyl lithium derivative of 63, prepared by exchange of iodine with lithium (chapter 8) with the Weinreb amide on the side chain gives the five-membered heterocyclic ring in 64, an intermediate on the way to (-)-brunsvigine 65, an alkaloid of the montanine group.14... 

Azidobenziodoxoles The noncyclic azido X -iodanes, for example, PhI(N3)OAc or PhI(N3)2, in general lack stability and rapidly decompose at -25 to 0 °C with the formation of iodobenzene and dinitrogen (Section 2.1.12.1). The incorporation of hypervalent iodine atom into a five-membered heterocycle leads to a significant stabilization of the azidoiodane. Stable azidobenziodoxoles 122-124 can be prepared by the reaction of hydroxybenziodoxoles 121 with trimethylsilyl azide in acetonitrile [251, 292], or by treatment of acetoxybenziodoxoles 125 with trimethylsilyl azide in dichloromethane in the presence of catalytic trimethylsilyl triflate (Scheme 2.43) [259]. All three azides 122-124 were isolated as thermally stable, non-explosive, microcrystalline solids that can be stored indefinitely in a refrigerator. 

Trifluoromethylbenziodoxoles The noncyclic CF3-substituted X -iodanes in general lack stability and cannot be isolated at room temperature however, the incorporation of a hypervalent iodine atom into a five-membered heterocycle has a significant stabilization effect. The first synthesis of stable trifluoromethylbenziodoxoles 157 and 159-161 by treatment of corresponding methoxybenziodoxole 156 or acetoxybenziodoxole 158 with trimethyl(trifluoromethyl)silane was reported by Togni and coworkers in 2006 (Scheme 2.52) [248]. 

A series of heterocyclic compounds containing trivalent iodine, oxygen and boron in a five-membered ring has been prepared by oxidative cyclization of commercially available orf/to-iodophenylboronic acids 182 and 185... 

Several heterocyclic compounds containing trivalent iodine, oxygen, and boron in a five-membered ring have been prepared by oxidative cyclization of the orifco-iodophenylboronic acids 168 and 171 (201IICI1263). 1-Chloro-4-fluoro-lH-lX -benzo[(/][l,2,3]iodoxaborol-3-ol 170 was formed in the reaction of 2-fluoro-6-iodophenylboronic acid 168 with chlorine followed by treatment of the intermediate iododichloride 169 with water. The... 

An unusual hypervalent iodine heterocycle 205 with condensed four-and five-membered rings has been prepared by oxidative cyclization of 3-iodo-3-hexene-2,5-diol 204 using neat icri-butylhypochlorite (Scheme 44 2001PSSS141, 2001JA1507). 

The five-membered pentavalent iodine heterocycles represent a particularly important class of hypervalent iodine compounds. Cyclic iodine(V) compounds, such as IBX 212 and DMP 213, have found broad practical application as mild and selective reagents for the oxidation of alcohols and some other useful oxidative transformations. Several comprehensive reviews of the chemistry and synthetic applications of IBX and DMP have been published (2011JOC1185, 2006ARK26, 2010T7659, 2011AGE1524, 2001ACE2812). 

Electrophilic Substitution. The rate constants and activation parameters for the formylation of selenophen by the DMF-phosgene complex in chloroform have been determined and compared with those of the other five-membered heterocycles. Acylation of 2-benzylselenophen occurs exclusively in the a-position of the selenophen ring. Formylation and acetylation of 2-(2-thienyl)selenophen went predominantly (80 and 75%, respectively) in the a-position of the selenophen ring and 20% in the a-position of the thiophen ring. 2,5-Dimethylselenophen-3-carboxylic acid could be iodinated at position 4 with iodine-iodic acid. Bromination of 2-formylselenophen in AlCh yielded the 4-isomer. Bromination of 2-methylselenophen with N-bromosuccinimide in acetic acid gave 3,5-di-bromo-2-methylselenophen. 

The intramolecular nucleophilic attack of a nitrogen atom on an allylpalladium complex was also used to construct a five and a six membered heterocycle in the same step. TV-substituted 2-iodobenzamides bearing an allene function in the appropriate distance from the iodine underwent cyclization through the carbopalladation of the allene moiety by the arylpalladium complex, formed in the first step of the catalytic cycle. The intermediate allylpalladium complex, part of a nine membered ring, cyclized readily to give the pyrroloisoquinolone derivative in excellent yield (4.23.). The nature of the added ligand and the solvent both had a marked influence on the efficiency of the transformation.26... 

Thionamides are the most important class of antithyroid compounds in clinical practice used in nondestructive therapy of hyperthyroidism. These agents are potent inhibitors of TPO, which is responsible for the iodination of tyrosine residues of thyroglobulin and the coupling of iodotyrosine residues to form iodothyronines. These drugs have no effect on the iodide pump or on thyroid hormone release. The most clinically useful thionamides are thioureylenes, which are five- or six-membered heterocyclic derivatives of thiourea and include the thiouracil 6-n-propyl-2-thiouracil (PTU) and the thioimidazole 1-methyl-2-mercaptoimidazole (methimazole, Tapazole, MMI). The uptake of these drugs into the thyroid gland is stimulated by TSH and inhibited by iodide. 

Cationic cyclizations, induced by hypervalent iodine reagents, are particularly useful in the synthesis of het-erocycles. Tellitu and Dominguez have developed a series of [bis(trifluoroacetoxy)iodo]benzene-promoted intramolecular amidation reactions, generalized in Scheme 3.134, leading to various five, six and seven-membered heterocycles 335 [388,389]. Experimental evidence supports the ionic mechanism of these reactions, involving A -acylnitrenium intermediates 334 generated in the initial reaction of the amide 333 with the hypervalent iodine reagent [390]. 

Synthesis of five- and six-membered heterocycles using molecular iodine (2006-2012) 12CEJ5460. 

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