Elimination substitution competition

Under conditions that usually lead to elimination rather than substitution, tosylates gave surprisingly good yields of substitution products. F. e. s. P. Veeravagu, R. T. Arnold, and E. W. Eigenmann, Am. Soc. 86, 3072 (1964) elimination-substitution competition s. a. A. Chambers and G. J. M. Sterling, Soc. 1965, 4556. 

Many secondary and tertiary halides undergo El elimination in competition with the SN1 reaction in neutral or acidic solutions. For example, when tert-butyl chloride solvolyzes in 80% aqueous ethanol at 25°, it gives 83% tert-butyl alcohol by substitution and 17% 2-methylpropene by elimination ... 

A proton on a y-carbon may be eliminated in competition with a proton on the a-carbon, and subsequent addition of the nucleophile to the central carbon atom of the intermediate substituted allene (189) would result in an overall substitution (equation 18). In this j8,y-elimination-... 

When 2-bromopropane (4.1) is allowed to react with the methoxide ion in methanol, only 40% of the starting material is converted into methyl isopropyl ether (4.2) (substitution) and the rest (60%) is transformed into propene (4.3) (elimination). Substitution and elimination are often competitive processes. The reaction that produces the alkene involves the loss of an HBr molecule to form a carbon-carbon double bond. 

Nucleophilic substitution and elimination are competitive processes. Which prevails depends on a variety of factors. One important consideration is the stability of the alkene that would result from elimination. Since tertiary halides form the more stable highly substitued alkenes, they are more likely to react by elimination than primary halides. 

The alkyl halide must be one that reacts readily in an Sn2 process. Thus, methyl and primary alkyl halides are the most effective alkylating agents. Elimination becomes competitive with substitution when secondary alkyl halides are used and is the only reaction observed with tertiary alkyl halides. 

It is apparent from section 2.5 that many factors influence the course of nucleophilic reactions, including the nature of the nucleophile, its strength, the solvent, the substrate and the nature of the leaving group. When substitution (sec. 2.7.A,B) and elimination (sec. 2.9.A,B) are discussed, it will be noted that they are sometimes competitive when using nucleophiles that are also bases, such as hydroxide. The same factors mentioned above influence the extent of this competition. If the functional groups in a molecule were such that substitution and elimination were competitive processes, then a mixture of products could result. It would be very useful to have a list of parameters for such situations that allow one to make predictions. This section will focus on several factors that influence both nucleophilic and elimination reactions. Analysis of these factors lead to key assumptions and predictions of the major product in many cases. 

In competition between substitution and elimination, substitution is favored by good nucleophiles and modest steric demands. Elimination is favored by strong, nonnucleo-philic, or bulky bases, low-polarity solvents, and high steric demand. 

For 4,5-dialkylthiazoles, the molecular ion decomposes by two competitive pathways, either loss of HCN followed by elimination of the radical R in the position /3 to the double bond of the resulting substituted thiirene, or by p cleavage followed by elimination of HCN (119). 

Section 8 13 When nucleophilic substitution is used for synthesis the competition between substitution and elimination must be favorable However the normal reaction of a secondary alkyl halide with a base as strong or stronger than hydroxide is elimination (E2) Substitution by the Sn2 mechanism predominates only when the base is weaker than hydroxide or the alkyl halide is primary Elimination predominates when tertiary alkyl halides react with any anion... 

This reaction mode of alkynylcarbene complexes of type 23 undoubtedly provides the most convenient access to /J-amino-substituted a,/J-unsaturated Fischer carbene complexes 27 (X=NH2, NHR2, NR2). Fischer et al. reported the very first such addition of an amine to an alkynylcarbene complex of type 23 and observed a temperature-dependent competition between 1,4- and 1,2-addition [12]. In a later systematic study, de Meijere et al. found that in addition to the 1,4-addition products 30,1,2-addition-elimination (formal substitution)... 

A complication of such reactions is competition from elimination reactions rather than substitution (see Section 18.5). (a) Predict the possible products from the reaction of 2-bromopentane with sodium hydroxide, (b) What can be done to favor the... 

An El reaction is generally accompanied by a competing SnI reaction, and a mixture of products is generally obtained. At the end of this chapter, we will explore the main factors that affect the competition between substitution and elimination reactions. 

Substitution and elimination reactions are almost always in competition with each other. In order to predict the products of a reaction, you must determine which mechanism(s) win the competition. In some cases, there is one clear winner. For example, consider a case in which a tertiary alkyl halide is treated with a strong base, such as hydroxide ... 

The mechanism of the nucleophilic substitution of a-halogenosulphoxides depends on structural factors and the nature of a nucleophile and may occur according to two competitive mechanisms a direct 8 2 substitution and an elimination-addition process . Thus, chloromethyl and bromomethyl sulphoxides react with alkoxide and mercaptide anions via an 8, 2 mechanism to give the corresponding a-alkoxy and a-alkylthiomethyl sulphoxides 502, respectively (equation 305). Optically active a-alkoxymethyl and a-alkylthiomethyl sulphoxides can also be obtained in this way - . 

Dehydration and RX formation from alcohols furnish another example of the competition between nucleophilic substitution and elimination. 

In order to explain the competitive formation of the 1 1 and 1 2 adducts and the formation of the 2,6-octadienyl rather than the 1,6-oc-tadienyl chain, a mechanism was proposed (62, 69) in which the insertion of one mole of butadiene to the Pd—H bond gives the 77-methallyl complex (68) at first, from which 1-silylated 2-butene is formed. At moderate temperature and in the presence of a stabilizing ligand, further insertion of another molecule of butadiene takes place to give C5-substituted n-allyl complex 69. The reductive elimination of this complex gives the 1 2 adduct having 2,6-octadienyl chain. In the usual telomerization of the nucleophiles, the reaction of butadiene is not stepwise and the bis-n--allylic complex 20 is formed, from which the l, 6-octadienyl chain is liberated. 

Enantioselective hydrogenation of 1,6-enynes using chirally modified cationic rhodium precatalysts enables enantioselective reductive cyclization to afford alky-lidene-substituted carbocycles and heterocycles [27 b, 41, 42]. Good to excellent yields and exceptional levels of asymmetric induction are observed across a structurally diverse set of substrates. For systems that embody 1,2-disubstituted alkenes, competitive /9-hydride elimination en route to products of cycloisomerization is observed. However, related enone-containing substrates cannot engage in /9-hydride elimination, and undergo reductive cyclization in good yield (Table 22.12). 

An early biphenyl candidate, A-331440 (6) has been reported to be a competitive, potent inverse agonist with balanced activity at human and rat H3Rs with good oral bioavailability [40]. While A-331440 was active in obesity models, its development was precluded by genotoxicity issues [41], The latter was eliminated by a tactical orf/zo-substitution on the phenoxy central core by fluorine to provide A-417022 (7). A-417022 and the 3,5-difluoro analog (A-423579) also produced prolonged weight loss over a 28-day period in a rat diet-induced obesity model [17,41],... 

We mentioned earlier in this section that when a sulfonyl group possesses a hydrogen on the carbon adjacent to the S02 group, an elimination-addition mechanism (193)—(194) for substitution, involving a sulfene as an intermediate, can be in competition with the direct substitution pathway and may, in fact, be preferred. Let us now discuss what is known about the mechanistic details of substitutions going by such an elimination-addition (sulfene) pathway, and the factors determining how readily such a process will occur under different conditions. 

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