Cyclization by bromine

Guanidine cannot be thioacylated by O-alkylchlorothioformates (RO—CS—Cl) the action of dialkylthiocarbonates [(RO)2CS], however, yields unstable intermediates (130) which are cyclized by bromine to 5-alkoxy-3-amino-l,2,4-thiadiazoles (131) in low yield (14.5% when R = Et).92... 

Acid hydrazides are cyclized by bromine cyanide in aqueous bicarbonate or other solvents to form 5-substituted 2-amino-l,3,4-oxadiazoles [Eq. (6)].48, 78,93, 94 The yields here are almost without... 

The thioanilides of a -cyanomalonic ester (520), which exist preferentially in their enethiol form, are cyclized by bromine to benzothiazolines (521) which can be decarboxylated to the corresponding 2-methylbenzo thiazoles (522 Scheme 282) (69CB351). 2-Bromo- or 2-chloro-thioacetanilides (523) undergo an intramolecular displacement of halogen on treatment with sodium hydride in TV-methylpyrrolidone or sodium methoxide in DMF, to give a correspondingly substituted 2-methylbenzothiazole (522 Scheme 283) (76S730). 

Oxidative cyclization by bromine converts the 1-carbamoyl- and 1-thiocabamoyl-benz-imidazoline-2-thiones (241) and (242) into the respective 2-substituted 2,3-dihydro-[l,2,4]thia-... 

Formamidinoyl isothiocyanates (66) react additively with amines to yield amidinothioureas (67), which are cyclized by bromine to yield substituted... 

Analogous cyclization reactions are induced by brominating reagents but they tend to be less selective than the iodocyclizations.83 The bromonium ion intermediates are much more reactive and less selective. 

Thiazolonaphthyridinium salts 331 can be produced either by bromination of the 2-alkenylpyridine precursor, or by thermal cyclization of the 2-(bromoacetyl)pyridine (Scheme 81) <1997CL1203>, and reaction of the pyrano-pyrimidine 332 with o-aminothiophenol gives the benzothiazole-fused pyridopyrimidinedione 333 (Equation 118) <2003JCCS887>. 

Several investigators have studied intramolecular Heck reactions on alkene-tethered haloindoles. Black prepared several l-allyl-7-bromoindoles and found that they undergo cyclization in the presence of palladium as shown for 242 to 243 [267]. Although this new synthesis of pyrroloquinolines is reasonably general, some of the products are unstable. Substrate 242 was prepared by bromination of 4,6-dimethoxy-2,3-diphenylindole (92%) and //-alkylation. 

Bromodesilylation T-methoxy-l-indanones. Cyclization contrary to the normal para-selectivity of anisole derivatives can be effected by temporary use of an ort/jo-trimethylsilyl group introduced by directed orf/io-metallation (11,75). Thus the anisole derivative 1 undergoes bromodesilylation and hydrolysis to provide 2. This product undergoes cyclization to 3 in good yield on conversion to the lithio salt followed by bromine-lithium exchange (8,65-66). 

Dibromo-l,4-xylene or its 2,5-dichloro derivative is obtained by bromination or, correspondingly, chlorination of 1,4-xylene. It is oxidized to form 2,5-dibro-moterephthalic acid or its dichloro derivative 59. Subsequent reaction with aryl-amine, for instance in the presence of copper acetate, affords 2,5-diarylamino-terephthalic acid 60. It is also possible to replace the halogen atoms stepwise by arylamino moieties [11]. Cyclization to form linear trans-quinacridones, as in the above-mentioned method, is achieved by using acidic condensation agents ... 

Syntheses of diastereomerically pure racemates of himachalene derivatives started from cycloheptanone G (Fig. 9). The sequence to I involved dimethyla-tion to yield H followed by bromination/dehydrobromination and conjugate methylation using cuprate chemistry. The sequence furnishing L and M follows a Robinson-annelation type Reaction of I with 3-(trimethylsilyl)but-3-en-2-one yielded K. Refluxing K with potassium hydroxide in ethanol removed the silyl group and cyclized the diketone to form a 97 3 mixture of racemic L and M. Occurring as a volatile in A.flava, L served as a versatile intermediate in the syntheses of other Aphthona compounds. 

The plan for a tandem cyclization as the key step in the synthesis of morphine alkaloids has been successfully performed [95]. Three examples are given in Scheme 7.10. Specifically, the initially formed aryl radical, generated by bromine abstraction from compound 74, underwent a tandem cyclization to construct the desired carbocyclic skeleton. Depending on the nature of the Z substituent to the double bond, the product radicals either abstracted hydrogen from silane (Z = C02Me or CN) or eliminated thiyl radical (Z = SPh). 

In a new method of ring enlargement of oxiranes to oxetanes, the intramolecular Williamson reaction is the essential last step. Reaction of an oxirane with selenomethyl-lithium reagents, followed by bromination, gives y-bromo alcohols, which can be cyclized by base to oxetanes. Since the oxiranes can be prepared readily from ketones and the selenomethyllithium reagent, this is also a synthesis of oxetanes from ketones (80TL585). 

Mild oxidation by bromine,101 iodine,10,28,103 or nitric acid101 cyclizes N-thioacylamidines (78) to 3,5-disubstituted 1,2,4-thia-diazoles (79).10,101,103 The synthesis has recently been extended to aliphatic members (79 R = alkyl or aryl) which are thus made available in 70-85% yield.28... 

Sorm and Beranek39 used an intramolecular acylation in their synthesis of l-azoniumtricyclo[3.3.3.0]undecane (66). Condensation of nitromethane with acrylonitrile in the presence of an alkaline catalyst resulted in the formation of tris-(2-cyanoethyl)nitromethane (60), which afforded the triethyl ester 61 on hydrolysis followed by esterification. The ester was reduced catalytically to give a pyrrolidone (62). The derivative (62) gave rise to 8-(j8-carboethoxyethyl)-3,5-dioxo-pyrrolizidine (63) on heating. Reduction of 63 resulted in the formation of 8-(y-hydroxypropyl)pyrrolizidine (64). Replacement of the hydroxy group by bromine (65), followed by cyclization, afforded the tricyclic compound 66. 

Condensation of 2-hydrazinopyrimidine (384) with an aromatic aldehyde formed the Schiff bases (386), which then cyclized with bromine to 6-bromo-l,2,4-triazolo[4,3-a]pyrimidine (383) and with carbon disulfide to 387 (92PS145). A similar cyclization was effected also on 384 to give 388 (68T2839 85FRP2549834), but the cyclization of 384 or 385 with carbon disulfide afforded 3-thiolo-l,2,4-triazolo[4,3-a]pyrimidin-7-ones 389 and 390, respectively. A small amount of the isomeric 3-thiolo-l, 2,4-triazolo[4,3-a]pyrimidin-5-one was isolated in the former case (68T2839). Reaction of 385 with benzaldehyde [67JCS(C)498] or p-chlorobenzaldehyde (90MI3) followed by oxidation with LTA in benzene afforded 391 (Scheme 73). 

Also cyclization of a six-membered chain has been reported. By brominating nonconjugated allylic amides, McManus et a/.165-166 obtained 5,6-dihydro- 1,3-oxazine derivative in addition to two other compounds (a five-membered ring and the brominated amide) [Eq. (32)]. 

The most likely course of this conversion involves H abstraction by bromine atoms. The resulting radical may undergo homolysis of the fullerene-silicon bond as outlined in Scheme 57. The silyl radical thus formed then undergoes intramolecular cyclization to give 132. While this type of intramolecular reaction readily occurs with radical species, it is not a common one in silicon ring systems. The Si-Si bond of 132 then must react with bromine followed by hydrolysis to give siloxane 131. 

Cyclization of dienes.3 Cp2Zr also promotes cyclization of 1,6-dienes to trans-1,2-disubstituted cyclopentanes. Thus 1,6-heptadiene (1) on treatment with Cp2Zr followed by bromination affords the trans-dibromide 2. In contrast, use of a related reagent, Cp ZrCl (Cp = pentamethylcyclopentadienyl), effects cyclization to the isomeric ds-dibromide (equation I). Electrophiles other than bromine can... 

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