Substitutions Bromination

The high nucleophilicity of sulfur atoms is preserved, even if it is bound to electron withdrawing carbonyl groups. Thiocarboxylales, for example, substitute bromine, e.g. of a-bromo ketones. In the presence of bases the or-acylthio ketones deprotonate and rearrange to episulfides. After desulfurization with triphenylphosphine, 1,3-diketones are formed in good yield. Thiolactams react in the same way, and A. Eschenmoser (1970) has used this sequence in his vitamin B]2 synthesis (p. 261). 

Unsymmetrically substituted dipyrromethanes are obtained from n-unsubstitued pyrroles and fl(-(bromomethyl)pyiToIes in hot acetic acid within a few minutes. These reaction conditions are relatively mild and the o-unsubstituted pyrrole may even bear an electron withdrawing carboxylic ester function. It is still sufficiently nucleophilic to substitute bromine or acetoxy groups on an a-pyrrolic methyl group. Hetero atoms in this position are extremely reactive leaving groups since the a-pyrrolylmethenium( = azafulvenium ) cation formed as an intermediate is highly resonance-stabilized. 

Since thiophene derivatives, heterocyclic aromatic compounds, are sensitive toward electrophilic substitution reactions, the bromination of these compounds generally gives a mixture of mono-, di-, and other poly-substituted bromination products (ref. 19). However, we have recently found that BTMA Br3 is a useful... 

Many substitution brominations are carried out with bromine. However, it may be advisable to resort to a cheaper material, BrCl, which can be easily made by reacting one mole of Bt2 with one mole of CI2. An additional advantage is that the outgoing product will be HCl and not HBr. Alternatively, in two-phase (liquid-liquid) reactions, we can additionally incorporate H2O2 so that HBr is converted in situ to Br2 which then gets transferred to the organic phase. An analysis of such new systems is required. 

Bromine was being added in portions to acrylonitrile with ice cooling, with intermediate warming to 20°C between portions. After half the bromine was added, the temperature increased to 70°C then the flask exploded. This was attributed either to an accumulation of unreacted bromine (which would be obvious) or to violent polymerisation [1], The latter seems more likely, catalysed by hydrogen bromide formed by substitutive bromination. Chlorine produces similar phenomena, even if the flask stays intact. The runaway is preceded by loss of yellow colouration and accompanied by formation of 3-chloroacrylonitrile and derivatives. It can be suppressed by presence of bases [2],... 

Substitution-defect pigments, 79 405 Substitutive bromination, 4 343-344 Substoichiometric sulfur burners, 23 660 Substrate additions, in microbial transformations, 76 411—412 Substrate materials... 

Due to their adverse health effects, several restrictions and bans have been imposed on the usage of polybrominated diphenyl ethers (PBDEs), namely the penta-, octa-, and deca-BDE formulations, in Europe, China, North America, and Japan (http //www. bsef.com). The restricted usage of these PBDEs increased the market demand for substitute brominated flame retardants (BERs) including hexabromocyclododecanes... 

I believe that it would be at least as powerful as DOM, due to the substituted bromine atom. As in most formulas, using nitromethane produces a product 10 times weaker than nitroethane use the one that suits you best. 

Chlorine monofluoride in nonpolar solvents is a more powerful electrophilic agent than hexa-chloromelamine in hydrogen fluoride. The latter is unable to substitute bromine at primary carbon atoms reacting only with tertiary and secondary bromides.106... 

Bromine trifluoride, neat or dissolved in liquid bromine, has found application for the selective substitution of fluorine for bromine (Table 3).108,109 The reactions are carried out at temperatures of no more than 60 C. Under these conditions no hydrogen substitution is observed. As established for bromofluoroethanes. the relative ease of replacement of bromine in various groups decreases in the order tribromomethyl > dibromofluoromethyl > dibromomethyl > bromofluoromethyl > bromomethyl. The presence of fluorine at either the same or an adjacent carbon tends to retard the substitution. Bromine trifluoride is more effeetive than antimony fluorides as it replaces bromine in bromodifluoromethyl and bromomethyl groups. 

This example demonstrates that the rule of thumb is an estimate at best. Most importantly, it is a reminder that the tertiary product will not necessarily be the primary product. Bromine is more selective than chlorine and substituting bromine for chlorine in the same reaction will result in predominately 2-bromo-2-methylbutane. Fluorine, on the other hand, is so reactive that the primary7 product would pre-dominate. 

Until a few years ago, no quantitative comparison of overall reactivities in electrophilic substitution of the fundamental five-membered rings was available. Only the reactivity of thiophene relative to benzene had been measured quantitatively in several electrophilic substitutions bromination,72 chlorination,72 nitration,121 hydrogen exchange,57 protodesilylation,174 and mercura-tion.121... 

Electrophilic substitution (bromination, nitration) of 2-substituted 1,2,3,6,7,116-hexahydro-4//-pyrazino[2,l -a]isoquinolin-4-ones occurred on the aromatic moiety to give either 11- or 8-substituted derivatives the site was not determined (76GEP2441261). The nitro group was reduced to an amino group, which was alkylated, acylated, and converted to different groups via a diazonium group, and involved in diazonium coupling. 

Another reagent that is quite useful in substituting bromine for hydrogen at allylic and benzylic positions is /V-bromosuccinimide (NBS) ... 

Lamparski LL, NestrickTJ (1989), Chemosphere 18 1761-1770.. .Micro-scale bromination procedure for synthesis of, 2,3,7,8-substituted" brominated dibenzo-p-dioxins and dibenzofurans from [lsC]-labeled precursors"... 

The route shown above is one of several ways to synthesize p- bromobenzoic acid and is definitely not the simplest way. (The simplest route is Friedel-Crafts alkylation -> bromination - oxidation). The illustrated synthesis shows the use of the diazonium replacement reaction that substitutes bromine for a nitro group. Oxidation of the methyl group yields the substituted benzoic acid. 

Interestingly, it has been observed that the ionization potentials (determined by the electron-impact technique) of several substituted five-membered heterocycles correlate with the substituent effects is larger than for benzene (p = —14.7) and larger than that measured for the most sensitive electrophilic substitution (bromination in acetic acid, which gives p = —10.0 for thiophene). As pointed out by Linda et al. [12], the sensitivity to substituent effects... 

From the researches of Baeyer [51] and Bloem it is shown that on brominating acetylortho-amidoacetophenone, the bromine atom enters in the methyl group. If the benzene chain is substituted brominated indigos are formed but if only the benzene chain contains bromine, indigo cannot be produced. In these reactions indoxyl appears to be formed as an intermediate product in the reaction. 

The thienoisoselenazole ring structure is prepared by treatment of the 3-formyl-2-ethyl-selenothiophene with bromine followed by ammonia (Scheme 16). In the case where there is no bromo substitution, bromination will take place at that 5-position <820MR(19)74>. The selenolo-isoselenazole is similarly prepared from the 2-formyl-3-methylselenide <87BSB407>. 

Reactions of naphthyridines including electrophilic substitution (bromination, nitration), nucleophilic substitution (amination, metallation), reduction, complexat-ion, etc., have been considered comprehensively in reviews (1970AHC123,... 

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