Halogeno-compounds

Platonov and G. G. Yakobson, The Application of Thermolylic Reactions for the Synthesis of Fluoro-organic Compounds , Synthesis, 1976, 374. 

Preparation.—A recent extensive review of fluorination methods in organic chemistry includes discussion of methods involving CF3OF (1,175), fluorine diluted with nitrogen (5,172), and fluoride ion as a nucleophile.A reported improvement to the hexachloroacetone-triphenylphosphine procedure for conversion of allylic alcohols to the chlorides (2, 148 4,158) is to use sulpholane as solvent rather than the hexachloroacetone, and to thus reduce the proportion of the latter reagent to 1 molar equivalent or less.  

Ishikawa, T. Kitazume, T. Yamazaki, Y. Mochida, and T. Tatsuno, Chem. Lett., 1981, 761. 

RCO2H A. H2CO3 + RCOjTl RBr Reagents i, TljCO ii, 1.5Br2-CCl4 reflux 

An electrochemical chlorination of isoprenoid-type alkenes in a methylene chloride-water-sodium chloride system to produce allylic chlorides has been reported [equation (9)] presumably Cr is generated by anodic oxidation as the reactive species. The selectivity of chlorination is affected markedly by the conditions, but trisubstituted terminal double bonds of the type shown in equation (9) are the most reactive. 

Uneyama, T. Nakai, and T. Yasuda, Tetrahedron Lett., 1981, 22, 2291. 

Preparation.—Alcohols (or their trimethylsilyl ethers) can be converted into alkyl iodides, with inversion at carbon, by reaction with trimethylsilyl iodide [equation (12)]. 

General and Synthetic Methods , ed. G. Pattenden (Specialist Periodical Reports), The Chemical Society, London, 1978, Vol. 1, Chapter 4. 

Kauffmarin, H. Ahlers, H.-J. Tilhard, and A. Woltermann, Angew. Chem. Internal. Edn., 1977,16, 710. 

Reagents i, PhSeBr-MeCN ii, O3 iii, Pr 2NH iv, PhSeBr-CCl4 v, H2O2 

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Several 4-amino-2,5-disubstituted thiazoles (257) have been obtained recently (702, 756, 776, 814, 820) by a ring cyclization reaction of halogeno compounds with cyanamide derivatives (263) according to the general Scheme 135. 

Halogeno compounds have been prepared by direct halogena-tion or by Sandmeyer reaction on 4-aminoisothiazoles. As expected from general considerations, a halogen atom in the 4-position is less reactive than one in the 5-position, but nitriles are obtained in good yield with cuprous cyanide at elevated temperatures. With butyllithium, lithiation occurs exclusively in the 5-position, and no evidence of halogen displacement has been obtained. ... 

Attempts to prepare selenazole derivatives were first described by Hofmann,2 a student of Hantzsch, in connection with investigations in the thiazole series. By reaction of selenobenzamide with a-halogeno compounds corresponding to the general reaction (2, R" = CeHg), he synthesized a series of 2-phenylselenazoles. In the same way, several... 

Arbusov reactions have been observed with many different types of reactive halogeno compounds, e.g. with polyhalogeno-alkanes,1 esters of halogenocarboxylic acids,2 alkylaryl halides3 and certain heterocyclic halides.4 5 Acetyl chloride and benzoyl chloride react at room temperature to give esters of the corresponding acetyl and benzoyl phosphonic esters. ... 

To establish which percentage of the label is present on the ring nitrogen and which on the amino group, the amino compound was converted by acid hydrolysis into 4-phenylpyrimidin-6(l//)-one, which was subsequently converted into 6-bromo-4-phenylpyrimidine (18a) by treatment with phosphoryl bromide (Scheme 11.12). If the content of the bromo compound 18a contains y%, the percentage of the 6-halogeno compound that reacts according to the Sn(ANRORC) mechanism can be calculated, i.e., (y X 100%. 

The reactions, usually carried out in organic solvents, proceed under mild conditions and often give high yields of the desired compounds. Compounds in which the hetero-atom bears one alkynyl group are better known than the "poly"-alkynyl derivatives. This can be explained in part by the readier availability of the mono-halogeno compounds R nYX and by a lower... 

They are isomeric with chloro-nitro-tetrammino-cobaltic chloride, [Co(NH3)4(N02)C1]C1.H20, and bromo - nitro - tetrammino - cobaltic bromide, [Co(NH3)4(N02)Br]Br.H20, the substances originally described by Jorgensen as aquo-salts. These salts are red, whereas all the aquo-nitro-salts are yellow in colour. Both salts are easily transformed into the isomeric nitro-halogeno-compounds on treatment with water.3... 

The replacement of the reactive 5-chloro by a sulfonamido group in 1,2,4-thiadiazoles affords a convenient synthesis of the 5-sulfonamido heterocycles.92- 3,168-172 173 Thus, 5-halogeno compounds (171), on treatment with p-acetamidobenzenesulfonamide and potassium carbonate in diphenyl ether at 200°, afford the sulfonamido derivatives (170) in 70 % yields. Nitrobenzenesulfonamides do not react. This route is valuable, because the products are obtainable with difficulty by sulfonylation of the parent amine (see Section III,D, 1,A).8-8S-86-87 The superiority of route 171 -> 170 over route 169-y 170, though unusual in the heterocyclic field, recalls similar observations made in the synthesis of sulfonamidotriazines.174... 

In alkaline media, 3-halogeno compounds appear to be less stable 3-chloro-5-phenyl-l,2,4-thiadiazole is decomposed completely by 1 Jf-alcoholic potassium hydroxide and by hydrazine.178 Nucleophilic substitution of the 3-halogen atom by alkoxy groups can be achieved, however, by means of sodium alkoxide in the appropriate alcohol 3-methoxy-, 3-benzyloxy-, and 3-(2 -hydroxyethoxy)-5-phenyl-l,2,4-thiadiazole are obtainable by this route in good yield.178... 

Substituted l,2,4-thiadiazol-5-yl diazonium tetrafluoroborates (314) react with potassium halides in acetonitrile in the absence of catalysts to afford the corresponding 5-halogeno compounds (315) in excellent yields.169 The isomeric 5-phenyl-l,2,4-thiadiazol-3-yl diazonium salts, however, resist substitution by this procedure, except with iodide ions by taking advantage of the catalytic effect of copper... 

Optical resolution of some hydrocarbonds and halogeno compounds by inclusion complexation with the chiral host (9a) has been accomplished.11,12 Preparation of optically active hydrocarbons is not easy and only a few example of the preparation of optically active hydrocarbons have been reported. For example, optically active 3-phenylcyclohexene has been derived from tartaric acid through eight synthetic steps.11 Although one-step synthesis of optically active 3-methylcyclohexene from 2-cyclo- hexanol by the Grignard reaction using chiral nickel complex as a catalyst has been reported, the enantiomeric purity of the product is low, 15.9%.11 In this section, much more fruitful results by our inclusion method are shown. 

Beckwith, A. L. S., Norman, R. O. C. Electron Spin Resonance Studies. Part XX. The Generation of Organic Radicals by the One Electron Reduction of Aliphatic Halogeno-Compounds in Aqueous Solution. J. Chem. Soc. A 1969, 400. 

The reaction of 2-mercapto-5-(phenylazo)-4,6-dimethylpyridine-2-carbonitrile with appropriate halogeno compounds yields S-alkylated products which can be cyclised to yield pyridothieno-pyrimidines (61a) or -triazines (61b) [94PS(90)85]. Related reactions have been employed to yield further fused ring heterocycles [95PS(104)143]. 

A large number of 5-unsubstituted thieno[2,3-d]pyrimidines 100 were obtained by reacting 5-formylpyrimidine-4(3//)-thiones 99 with the appropriate a-halogeno compound (ethyl bromoacetate, phenacyl bromide, chloroacetonitrile or chloroacetamide) in aqueous sodium carbonate at 50°C (93JHC1065). 

When 5-acetylpyrimidine-4(3//)-thiones 101 are cyclocondensed with a-halogeno compounds, 5-methylthieno[2,3-d]pyrimidines 102 are obtained. The isolation of 5-alkyl intermediates in these synthesis was sometimes unpredictable. 

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