Secondary alkyl bromides

Place a mixture of 0-5 g. of finely powdered thiourea, 0-5 g. of the alkyl halide and 5 ml. of alcohol in a test-tube or small flask equipped with a reflux condenser. Reflux the mixture for a j)eriod depending upon the nature of the halide primary alkyl bromides and iodides, 10-20 minutes (according to the molecular weight) secondary alkyl bromides or iodides, 2-3 hours alkyl chlorides, 3-5 hours polymethy lene dibromides or di-iodides, 20-50 minutes. Then add 0 5 g. of picric acid, boil until a clear solution is obtained, and cool. If no precipitate is obtained, add a few drops of water. RecrystaUise the resulting S-alkyl-iso-thiuronium picrate from alcohol. 

Other alkylbenzenes may be prepared similarly by using the appropriate primary or secondary alkyl bromide. 

Additional evidence for carbocation intermediates in certain nucleophilic substitutions comes from observing rearrangements of the kind normally associated with such species For example hydrolysis of the secondary alkyl bromide 2 bromo 3 methylbutane yields the rearranged tertiary alcohol 2 methyl 2 butanol as the only substitution product... 

A considerable amount of hydrobromic acid is consumed in the manufacture of inorganic bromides, as well as in the synthesis of alkyl bromides from alcohols. The acid can also be used to hydrobrominate olefins (qv). The addition can take place by an ionic mechanism, usually in a polar solvent, according to Markownikoff s rule to yield a secondary alkyl bromide. Under the influence of a free-radical catalyst, in aprotic, nonpolar solvents, dry hydrogen bromide reacts with an a-olefin to produce a primary alkyl bromide as the predominant product. Primary alkyl bromides are useful in synthesizing other compounds and are 40—60 times as reactive as the corresponding chlorides (6). 

Sodium nitrite can be used to form nitro compounds with primary or secondary alkyl bromides or iodides, though the method is of limited scope. Silver nitrite gives nitro compounds only when RX is a primary bromide or iodide. Nitrite esters are an important side product in all these cases (10-33) and become the major product (by an SnI mechanism) when secondary or tertiary halides are treated with silver nitrite. 

Triphenylmethylpotassium rapidly dehydrohalogenates secondary alkyl bromides and iodides, in over 90% yields, at 0 C Anton, D.R. Crabtree, R.H. Tetrahedron Lett., 1983, 24, 2449. 

The scope of this reaction was extended to secondary alkyl bromides with IBiox ligands that are both sterically hindered and flexible carbenes [129]. Secondary... 

Scheme 6.43 Sonogashira coupling with secondary alkyl bromides...

Organolithium reagents in which the carbanion is delocalized are more useful than alkyllithium reagents in alkylation reactions. Allyllithium and benzyllithium reagents can be alkylated and with secondary alkyl bromides and a high degree of inversion of configuration is observed.78... 

An alternative protocol for treating alkylzinc bromides with primary and secondary alkyl bromides and iodides was described by Zhou and Fu.409 In the study, a combination of Ni(cod)2 and a chiral oxazoline ligand 306 was used as a catalytic system providing 62-88% yield of product 307 A,A-dimethylacetamide (DMA) was the reaction solvent (Scheme 156). 

Reactions of potassium superoxide solubilized in apolar solvents with crown ethers (see Oxidation reactions, p. 356) are also frequently accompanied by elimination reactions. Thus, in DMSO solution, secondary alkyl bromides only yield olefins when treated with the K02 complex of dicyclohexyl-18-crown-6 (Johnson et al., 1978). Scully and Davis (1978) have studied the elimination of HC1 from N-chloramines with 18-crown-6-solubilized K02, KOH, and KOAc in ether solution (27). High yields of aldimines were obtained with K02,... 

Recently, Fu and coworkers have shown that secondary alkyl halides do not react under palladium catalysis since the oxidative addition is too slow. They have demonstrated that this lack of reactivity is mainly due to steric effects. Under iron catalysis, the coupling reaction is clearly less sensitive to such steric influences since cyclic and acyclic secondary alkyl bromides were used successfully. Such a difference could be explained by the mechanism proposed by Cahiez and coworkers (Figure 2). Contrary to Pd°, which reacts with alkyl halides according to a concerted oxidative addition mechanism, the iron-catalyzed reaction could involve a two-step monoelectronic transfer. 

Under these conditions, a broad range of polyfunctional alkyl iodides are converted to the corresponding organozinc halides in high yields . In the case of primary alkyl iodides, the insertion occurs at 40-50 °C whereas secondary alkyl iodides already react at 25-30°C. Secondary alkyl bromides also react under these conditions , but primary alkyl bromides are usually inert with this type of activation and much better results are obtained by using Rieke zinc L Thus, the reduction of zinc chloride with finely cut lithium and naphthalene produces within 1.5 h highly reactive zinc (Rieke zinc). 

This has led to the discovery of electron-deficient styrenes, such as those shown in Figure 2. As detailed later, these ligands have been shown to be effective for the Ni-catalyzed alkylation of organozincs with primary alkyl iodides and bromides91. More recently, Fu88k has reported that a catalyst consisting of Ni(COD)2 and s-Bu-Pybox (3) is satisfactory even for the reaction of primary alkylzincs with secondary alkyl bromides... 

Cycloalkyl and secondary alkyl bromides react with N02 BF4 in pyridinium poly(hydrogen fluoride) solution to yield /J-fluorinated compounds in moderate to good yields. In the case of the cyclic starting materials like 1-bromocyclohexane only trans-substituted products are formed (see Table 22). 

The lower yields are due in some cases to the difficulty of isolating the products, and, in the last two, to the less complete reaction between the secondary alkyl bromide and the sodium derivative of ethyl acetoacetate. 

When stabilized (and consequently less reactive) anions are employed as the nucleophile, more reactive electrophiles are needed for successful carbon-carbon bond formation. Nitronate anions, which are highly resonance stabilized, fail to react widi simple alkyl hahde electrophiles. On the other hand, /3-dicarbonyl compounds react effectively with primary and some secondary alkyl bromides and iodides to give monoalkylated products. 

Alkyl- or aryl-iridium(I) complexes IrR(CO)L2 (R = CH3, C6H5 L = PMe3, PMe2Ph) will oxidatively add secondary alkyl bromides or iodides to give octahedrally coordinated bis(alkyl)iridium(III) complexes, as exemplified in Equation 1. 

More than half of a secondary alkyl bromide undergoes elimination under the same conditions, as we have already seen. 

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