Halide substitution

Some instances of incomplete debromination of 5,6-dibromo compounds may be due to the presence of 5j5,6a-isomer of wrong stereochemistry for anti-coplanar elimination. The higher temperature afforded by replacing acetone with refluxing cyclohexanone has proved advantageous in some cases. There is evidence that both the zinc and lithium aluminum hydride reductions of vicinal dihalides also proceed faster with diaxial isomers (ref. 266, cf. ref. 215, p. 136, ref. 265). The chromous reduction of vicinal dihalides appears to involve free radical intermediates produced by one electron transfer, and is not stereospecific but favors tra 5-elimination in the case of vic-di-bromides. Chromous ion complexed with ethylene diamine is more reactive than the uncomplexed ion in reduction of -substituted halides and epoxides to olefins. ... 

Aminolysis of the corresponding halides is the preferred method for the synthesis of dialkylamino derivatives of boron,1 silicon,2 germanium,3 phosphorus,4 arsenic,5 and sulfur.6 (Dialkylamino) chlorosilanes are prepared stepwise by the reaction of silicon tetrachloride with dialkylamines. This method may be utilized equally well for the conversion of alkyl- or aryl-substituted halides [e.g., (CH3) SiCl4. ] or of oxide and sulfide halides (e.g., POCl3 or PSC13) to the corresponding dialkylamino compounds. 

By applying alternative alkylation and cathodic cleavage Horner etal S07 synthesized optically active phosphines and phosphonium salts. In reversal of their usual application as reageqts in nucleophilic substitution halides, if converted to... 

The presence of group 4 metals P to a carbenium ion has a dramatic effect on the stability of the carbenium ion, a remarkable phenomenon known as the P-effect.12 29, 30 The silicon P-effect was discovered in 1937 by Ushakov and Itenberg,31 who noted the exceptional reactivity of P-silyl-substituted halides R3SiCH2CH2X towards elimination (Scheme 1). The effect has since been the subject of many mechanistic32-36 and theoretical studies37-39 and several reviews.10-12,29... 

In the El reaction, the rate-limiting step is formation of a carbocation, and the reactivity order reflects the stability of carbocations. In the E2 reaction, the more substituted halides generally form more substituted, more stable alkenes. 

Identity of R More substituted halides react fastest. 

More substituted halides react fastest Rate R3CX > R2CHX > RCHjX Favored by strong bsises Better leaving group — faster reaction Favored by polar aprotic solvents... 

Olefin formation with 1,2-dihalides or /1-alkoxy-substituted halides , e.g. ... 

A general approach to P-functional alkanols involves formation of a-substituted samarium reagents and their reaction with carbonyl compounds. Thus, P,P-diiodoalkanols, °. -iodohydrins, " P-phenylselenoalkanols, and P-phenylthio-alkanols are prepared from the corresponding substituted halides. The products with a syn disposition are predominant. 

Good nucleophiles are required if an aryne or hetaryne is to be trapped by other than the base employed for its generation. This is an important limitation for syntheses. Among the best nucleophiles are those with sulfur77 78) or carbon centers. Isomer formation is another limitation. This is especially severe with meta substituted halides which can dehydrohalogenate to give two intermediates which then can react with a nucleophile to form three isomers. However, by carefully selecting a halide so that only one intermediate results and one product isomer is favored, useful syntheses are possible. 

As can be seen in Scheme 11, various procedures have been established for the further derivatization of dinuclear gold(II) ylide complexes by ligand substitution. Halide ligands can be substituted by neutral donor ligands such as tetrahydrothiophene or pyridine (giving the corresponding cationic complexes)249, or with other anionic ligands (such as... 

The authors point out that the substituted bromo- and chlorobenzenes fall into two classes based upon the magnitude of the accelerating effect of the substituent upon the reaction rate and the relationship between the rates of the m- and p-substituted halides. Class I comprises the substituents CH3O, HO, Cl and F for which the rate coefficient sequence is o >m>p>u(u = unsubstituted) and Class II comprises the substituents CN and CH3 OOC for which the sequence iso>p>m>u and for which the substituent effects are more powerful. These variations are understood in terms of the negative group effect, it being expected that the extra stabilization of the transition state decreases as the X and Y substituents are further separated from one another. The Class II substituents exhibit a more powerful accelerating effect because of the character of the multiple... 

Noteworthy, are the superior yields for coupling of amines with orfho-substituted halides and halopyridines. [15c] In case of the synthesis of aminopyridines the improved catalyst activity is explained by the ability of chelating ligands to prevent formation of bis-pyridyl palladium complexes that terminate the catalytic cycle. Interestingly, electron rich aryl bromides (entry 2) gave similar high yields as electron poor aryl halides (entry 1). The sterically hindered aryl bromide 1-bromo-2,5-dimethylbenzene can be coupled with A-methylpiperazine even in the presence of just 0.05 mol % palladium (entry 4). Thus, catalyst turnover numbers up to 2000 were realized for the first time. When primary amines are used, just small ammounts of double arylated products were detected. 

Substituted halides are said to react depending on the position and nature of the substituents. For example CH2=CH(CH2)3C1 does not react, yet the corresponding bromide does. Allyl halides react, vinyl halides do not. Substituted vinyl halides, however, do react (45,46). 

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