Imines bromination

Carbon-nitrogen multiple bonds in fluorinated imines and nitriles react with halogen fluoride reagents Imines provide 7V-chloroamine.s on reaction with chlo rme fluoride [62, 121, 122, 123] (equations 23 and 24) or with cesium fluoride and chlorine [124] and A -bromoammes on reaction with cesium fluoride and bromine (equation 24)... 

Generally, the addition of chlonne or bromine to tnfluoroacetonitrile leads to a mixture of partially halogenated imines, amines and azo alkanes [270, 271] In special cases, such as the HgF2-mediated addition of bromine, N,N dihaloper-fluoro-2-alkylamines can be obtained in good yields [272]... 

More expedient from the preparative point of view is the method based on compounds 6, which can be obtained in high yields by the addition of bromine to (3-methyltellurovinylaldehydes [96ZOK1434 97JOM(536-537)233], When treated in benzene solution with ammonia, (3-methyldibromotellurovinylaldehydes 6 afford isotellurazoles lg,h in about 70% yields [97DOK(357)504], The key step of the reaction is the elimination of a molecule of methyl bromide from the intermediate imine 7. 

The oxidation of /(-amino-substituted iron acyl complexes which are prepared via condensation reactions of iron-acyl enolates and imines or iminium ions26,5 -47-54 generates /(-lactams 32,33,61. Brief treatment with bromine in dichloromethane at low temperature is the usual procedure. 

TL5981>. The proposed mechanism involves the oxidation of the amine to an imine, tautomerization to an enamine, and a sequence of nucleophilic attacks on the pyridazine rings followed by oxidation steps. The oxidant of choice is (bispyridine)silver permanganate <1982TL1847>, which is easily prepared, mild in action, and is soluble in organic media. If R1 = H in the product 77, electrophilic substitution (e.g., bromination, nitration, Mannich, and Vilsmeier-Haack-Arnold reactions) occurs at this position. 

This method has been extended to include arylhydrazono thioacetamides, such as 75, which undergo oxidative cyclization using bromine to afford 2-aryl-1,2,3-thiadiazol-5(277)imines 76 (Equation 23) <2004RJ0818>. 

It turned out that the requirements of such a chiral d reagent are fulfilled by the l-bromo-l-lithio-l-aUcenes S- and /f-41, which are available from the corresponding enantiomer of lactate . When added to aldehydes or imines, significant diastereose-lectivity will be displayed only by the fi-diastereomer 41. Thus, the selective exchange of the bromine atom in the Z-position of the dibromoaUcene 40, outlined in Scheme 9, is prerequisite to the efficiency of this concept. 

This ready nucleophilic substitution at the 6-position is surprising since this position is electron-rich in both dihydrodiazepines and dihydrodiaze-pinium salts and is the site at which electrophilic substitution occurs. The likely explanation is that in the presence of base some prototropic rearrangement of the normal dihydrodiazepine base into a bis-imino form takes place. Although the equilibrium concentration of the bis-imine is likely to be very small (it has not been observed spectroscopically) it would be strongly electrophilic at the 6-position owing to the combined effects of the bromine atom and the two azomethine groups, and could well be the reactive species in the nucleophilic substitution of the bromine atom ... 

The oxidative metabolism leads to the formation of reactive species (epoxides, quinone-imines, etc.), which can be a source of toxicity. Consequently, slowing down or limiting these oxidations is an important second target in medicinal chemistry. Thus, the metabolism of halothan (the first modern general anaesthetic) provides hepatotoxic metabolites inducing an important rate of hepatitis the oxidation of the non-fluorinated carbon generates trifluoroacetyl chloride. The latter can react with proteins and lead to immunotoxic adducts [54], The replacement of bromine or chlorine atoms by additional fluorine atoms has led to new families of compounds, preferentially excreted by pulmonary way. These molecules undergo only a very weak metabolism rate (1-3%) [54,55]. 

One of the two classic schemes for constructing the thiazole ring involves the condensation of a thioamide or its equivalent with an a-haloketone. The reaction can be visualized as involving, as the first step, the displacement of halogen by sulfur from the enol form of the amide imine formation will then close the ring. Thus, reaction of bromoketone (99-2) obtained from the bromination of the corresponding keto-acid with thioamide (99-1) affords thiazole (99-3) in a single step. There is thus obtained the NSAID fentiazac [109]. 

In a similar vein, reaction of the thiobenzamide (100-1) with 4-bromoacetoacetate (100-2) in the presence of a base starts by the displacement of bromine by sulfur to afford a transitory substimtion product such as (100-3). This can then undergo internal imine formation between basic nitrogen and the adjacent carbonyl goup to afford the thiazole (100-4). Saponification then leads to the NSAID fenclosic acid (100-5) [110]. 

No extensive investigation of mechanism has been undertaken for any of the methods of dehydrohalogenation described. 17-Bromo-20-ketones appear to undergo preferential trcms-e imination.31 111 2-Halo-3-ketones suffer predominant loss of the la (axial) hydrogen, but the geometry of bromine loss is not known.112 7ra/w-diaxial elimination has sometimes been assumed in configurational assignments,113 but this is not necessarily correct (see ref. 6). 

Tropolone complexes (20) also undergo electrophilic substitution, but the numerous positions for reaction give rise to mixtures of products. The p-keto imine complexes (21) and (22)32 have been brominated successfully using )V-bromosuccinimide. 

Benzoquinone l,4-di(bromo imine), BrN C6H4 NBi mw 263 94, N 10.62% crysts, mp expl ca 86, was claimed to have been prepd by Krause(Ref 2) by treating an aq soln of p-phenylenediamine chloride with an excess of bromine water. No an-analysis of the compd was given Refs l)Beil- not found 2)A.Krause,Ber 12,50... 

Terminally brominated PE as PE macroinitiator can be produced by other methods. It has been reported that vinyl terminated PE produced by a bis(phenoxy-imine)metal complex and MAO catalyst system (Mn = 1800, Mw/Mn = 1.70) was converted to terminally 2-bromoisobutyrate PE through the addition reaction of 2-bromoisobutyric acid to the vinyl chain end. Polyethylene-Wodc-poly( -bulyl acrylate) (PE-fo-PnBA) from terminally brominated PE by ATRP procedure has also been produced [68]. It was reported that degenerative transfer coordination polymerization with an iron complex can be used to prepare terminally brominated PE as a macroinitiator [69]. A Zn-terminated PE prepared using an iron complex and diethylzinc,... 

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