Oxidative ring closure

Oxidative Ring Closure Reactions 4.03.4.1.1 C—N bond formation N—N bond formation C—S bond formation N—S bond formation O—C bond formation O—N bond formation S—S, S—Se and Se—Se bond formation Electrophilic Ring Closures via Acylium Ions and Related Intermediates Ring Closures via Intramolecular Alkylations... 

Although some of the oxidative ring closures described above, e.g. reactions with lead tetraacetate (Section 4.03.4.1.2), may actually involve radical intermediates, little use has been made of this reaction type in the synthesis of five-membered rings with two or more heteroatoms. Radical intermediates involved in photochemical transformations are described in Section 4.03.9. Free radical substitutions are described in the various monograph chapters. 

Maybe the best well-estabhshed method for the preparation of Bfxs is the oxidative ring closure of o-nitroanihne derivatives. AlkaUne hypochlorite, NaOCl/KOH, has been the most commonly used reagent but electrochemical synthesis [17] and bis(acetate-0-)phenyUodine as oxidizer have also been employed [18]. The procedure is particularly useful where the other... 

The oxidative ring-closure method is well known. Halo-substituted benzofurazans are obtained by reaction of aqueous sodium hypochlorite with potassium salts of the corresponding 2-nitroanilines (Equation 79) <2001SC2329, 2002BML233, 2003HCA1175, 2003JFC(121)171, 20030PD436>. 

Synthesis of [1,2,3]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-c]pyrimidines A novel approach to [l,2,3]triazolo[l,5-c]pyrimidines is shown in Scheme 55. Batori and Messmer - in the course of their investigations on fused azolium salts - described a synthetic pathway to l,3-disubstituted[l,2,3]triazolo[l,5-c]-pyrimidinium salts <1994JHC1041>. The cyclization was accomplished by transformation of the hydrazone 436. This compound was subjected to an oxidative ring closure by 2,4,4,6-tetrabromo-2,5-cyclohexadienone to give the bicyclic quaternary salt 437 in acceptable yield. 

The chromophore part was prepared from Boc-protected N, A-dimethyl-L-DOPA (91), reduction to the diamine 92 and tellurium-mediated oxidative ring closure (93). The free amino group of 94 was coupled with protected L-Ser and L-Thr-o-Ser (95) and then the two constituent parts were coimected and deprotected yielding 10 121). 

De Jong and Janssen obtained 68% of the sulfide 175 from 3-thienyllithium and bis(phenylsulfonyl)sulfide. Dilithiation of 175 followed by oxidative ring closure afforded dithienothiophene 6 (52%) [Eq. (50)]. Similarly, 3-bromo-2-thienyllithium (180) gave 3,3 -... 

A 94% yield of 3,4 -dibromo-2,3 -dithienyl sulfide (184) was similarly achieved from 3-bromo-2-thienyllithium (180) and disulfide 182. Oxidative ring closure of the dilithium derivative of 184 gave dithienothiophene 8 in 29% yield [Eq. (53)]. 

Selective bromination of monobromo-substituted dithienyl sulfides with iV-bromosuccinimide afforded two more dithienothiophene isomers. From the reaction of 3-thienylIithium with disulfide 182 at —70°, 4-bromo-3,3 -dithienyl sulfide (185) was isolated. Bromination with 7 T-bromosuccinimide provided 2,4 -dibromo-3,3 -dithienyl sulfide (186) dilithiation of the latter followed by oxidative ring closure gave dithienothiophene 9 in 13% overall yield [Eq. (54)]. 

Similar oxidative ring closures by singlet oxygen (methylene blue as sensitizer, - 78°C) have also been reported by Dutch workers [87JCS(P1)-2481]. For instance, (42) gave a mixture of the two diastereomers (43) and (44). 

The benzo fused system (579) is produced in good yield by the oxidative ring closure of (578) or by the action of zinc and aqueous sodium hydroxide on (577) (55CB1284). It rearranged in dilute acetic acid to give 3-phenyl-l,2,4-benzotriazine. 

The ability of palladium(II) acetate to mediate the oxidative ring closure of indole derivatives containing a pendant aromatic ring has been exploited... 

The use of a stoichiometric amount of palladium acetate, a fact that biases the original oxidative ring closure reactions, can be overcome by the use of an oxidant in the process, which re-oxidizes palladium(O) that is formed in the final step of the ring closure. Such a transformation is presented in 3.78., where an anilino-benzoquinone was ringd closed to give an indoloquinone in the presence of a catalytic amount of palladium acetate and a stoichiometric amount of copper(II) acetate.98... 

Several examples of oxidative ring closures by attack on an azomethine group by an amine have been reported78 thus arylidene-o-phenylenedi-amines (32) have been oxidized to 2-arylbenzimidazoles (33) [Eq. (35)]. 

Oxidative ring closure by formation of a nitrogen-nitrogen bond may be obtained, using suitable heterocyclic hydrazones, formazans, and certain other azomethine functions as substrates. 

In the previous examples, the sulfur atom acted as a nucleophile. Electron-deficient sulfur species such as sulfenyl ion and its equivalents (e.g. disulfide/Lewis acid complexes, sulfenic acids, sulfenyl halides, sulfonium ions, sulfines, etc.), can also serve as an electrophile. Oxidative ring closure of enethiols (a-thioketocarboxylic acid) (124), which proceeds via disulfides, produces thiophenes (125) in good yields (86EUP158380, 88JHC367). 

Pyrazines are obtained by oxidative ring closure of bis(acylmethyl)amines (304) with ammonia. 

Oxidative ring closure on to a ring nitrogen atom occurs readily as in the formation of the [ 1,2,4]thiadiazolo[2,3-a]pyridine (78) from the 2-pyridylthiourea (77) (75JHC1191). Similarly, bromine oxidation of 2-thiazolylthiourea (79) gives the 2-aminothiazolo[3,2-/ ] [l,2,4]thiadiazolylium bromide (80) (71JPR1148). 

Compounds containing an ylidic N—S bond are best considered as cyclic sulfimides, and as such can be prepared by methods used for their acyclic counterparts (77CRV409). For example, oxidative ring closure of (181) with bromine gives the cyclic sulfimide (93) (64LA(675)189), and treatment of JV-(2-phenylthio)phenylbenzamidine with N-chlorosuc-cinimide (NCS) leads to the cyclic sulfimide (182) (78CC1049). 

Oxo dithioic acids react with a combination of (Me3Si)2S and A-chlorosuccinimide in the presence of imidazole to give oxidative ring closure to the 3//-l,2-dithiole-3-thiones (equation 21)39. 

The first example reported in the literature is the cyclization of dihydrobilin to octadehydrocorrin [51-54]. The reaction is catalyzed by the presence of nickel or cobalt salts. As in the case of corrole and its metal complexes such ring closure reaction has been carried out in alcoholic solution, it is oxidative and base catalyzed. It has been demonstrated that the formation of the corrin ring is part of an equilibrium where the oxidative ring closure is coupled with a reductive ring opening reaction [55]. 

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