Secondary substituted product

In the latter cases, steric and electronic factors facilitate the formation of small amounts of secondary substituted products. 

The reported 2731 yield of adamantanone oxime from this reaction (63 %) is misleading since it is based on Cl2 as the limiting reagent. Careful product analyses have shown that the overall ratio of tertiary to secondary substitution products ( 2) is quite normal275), While this reaction is clearly much less useful for the preparation of methylene substituted adamantanes than the ionic processes discussed above, it may be applicable in more specialized cases such as, for example, the synthesis of polyalkylsubstituted adamantanones where the ionic processes work poorly. 

Unlike the addition of halogens across double bonds, addition of acids results in formation of asymmetrical products. Specifically, a different group is added to each side of the double bond. Thus, if this reaction is applied to asymmetrical olefins such as propene, multiple products might be expected to form as illustrated in Scheme 7.8. In fact, while a mixture of products is formed, there is an overwhelming presence of the secondary substituted product compared to that with substitution at the primary position. This preference of reaction products resulting from addition of protic acids across double bonds is governed by Markovnikov s rule. 

Most of the early mechanistic studies that focused on the S ,j2 versus 8 2 nucleophilic substitution by an organometallic reagent were made with allylic halides. In the late 1940s, Wilson [7] showed that phenylmagnesium bromide reacted with a- and y-methylallyl chlorides 1 and 2, respectively, to afford a nearly identical mixture of primary and secondary substituted products 3 and 4, respectively, in a 75 25 ratio [Eq. (1)]. 

It should be noted that the a-haloketones reported in Table 4 are characterized by their aptitude to yield secondary substitution products. This peculiar reactivity is related to the fact that the halogen is axial, which favors formation of a-methoxyketone and a-hydroxyketone simultaneously. 

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... 

Hydrogen sulfide ion HS and anions of the type RS are substantially less basic than hydroxide ion and react with both primary and secondary alkyl halides to give mainly substitution products... 

An important extension of these reactions is the Mannich reaction, in which aminomethyl-ation is achieved by the combination of formaldehyde, a secondary amine and acetic acid (Scheme 24). The intermediate immonium ion generated from formaldehyde, dimethyl-amine and acetic acid is not sufficiently reactive to aminomethylate furan, but it will form substitution products with alkylfurans. The Mannich reaction appears to be still more limited in its application to thiophene chemistry, although 2-aminomethylthiophene has been prepared by reaction of thiophene with formaldehyde and ammonium chloride. The use of A,iV-dimethyf (methylene) ammonium chloride (Me2N=CH2 CF) has been recommended for the iV,iV-dimethylaminomethylation of thiophenes (83S73). 

Extension of this reaction to other substrates, however, revealed that it is more complex, and that side products are formed depending on (1) the nature of the substrate, (2) the reaction conditions, e.g. temperature and solvent,and (3) the method of work-up." Thus, in addition to the desired substitution products, primary and secondary hydroxy steroids generally yield esters and ethers and undergo simple dehydration as well as dehydration accompanied by rearrangement. 

The alkylation reaction is limited to the use of primary alkyl bromides and alkyl iodides because acetylide ions are sufficiently strong bases to cause dehydrohalogenation instead of substitution when they react with secondary and tertiary alkyl halides. For example, reaction of bromocyclohexane with propyne anion yields the elimination product cyclohexene rather than the substitution product 1-propynylcyclohexane. 

Chloromethyl)quinazoline 3-oxides, c.g. 8, react with ammonia and primary amines to yield 3//-1,4-benzodiazepine 4-oxides 10, sometimes accompanied by the simple substitution products 9.219 Dimethylamine220 and pyrrolidine221 react analogously, but other secondary amines afford only products of type 9. 

To sum up, primary and secondary substrates generally react by the Sn2 mechanism and tertiary by the SnI mechanism. However, tertiary substrates seldom undergo nucleophilic substitution at all. Elimination is always a possible side reaction of nucleophilic substitutions (wherever a P hydrogen is present), and with tertiary substrates it usually predominates. With a few exceptions, nucleophilic substitutions at a tertiary carbon have little or no preparative value. However, tertiary substrates that can react by the SET mechanism (e.g., /i-N02C6H4CMe2Cl) give very good yields of substitution products when treated with a variety of nucleophiles. ... 

The high yields—about 50%—which were observed in all cases, indicate the strong involvement of secondary fission products (i.e., those produced by /S-decay of precursors). A consideration of mechanisms of formation of the organometallic products led to the conclusion (13) that the j8-decay itself must be the cause of the molecule formation. Neither purely mechanical collisional substitution, nor thermal chemical reactions, nor radical reactions, nor radiation-induced reactions seemed to be responsible for the synthesis reactions. 

It should be noted at this point that primary and secondary reaction products can be distinguished not only by kinetic data (13) but also by suppression of the secondary reactions. E.g substitution of 2,2,2-trifluoroethanol for p-dioxane as solvent for HCoCCO) suppresses homologation and methane formation addition of a phosphine to give the less acidic catalyst HCo(CO)3PR3 has the same effect, as has the substitution of the less acidic catalyst HMn(CO)5. 

Typically, the organic substrate in these reactions is a haloalkane. Primary haloalkanes will generally give 100% substitution products, but tertiary and cyclohexyl halides usually undergo 100 % elimination, with secondary haloalkanes producing a mixture of the two. Studies of the chloride and bromide displacements of (R)-2-octyl methanesulfonate have shown that phase transfer displacements proceed with almost complete inversion of stereochemistry at the carbon centre, indicating an Sjv2-like mechanistic pathway [41],... 

This kinetic feature is observed by using primary and secondary amines, both aromatic and aliphatic. Tertiary amines263 (and other substances unable to produce substitution products such as 2-hydroxypyridine264) may act as a catalyst in apolar solvents, in a series of runs carried out without changing the initial concentration value of substrate and of amines, it was found that the addition of tertiary amines enhances kabs values. 

The substituent effects on the photochemistry between benzene and secondary aliphatic amines53 were studied. Irradiation of toluene or chlorobenzene with diethylamine results in the formation of mixtures of addition and substitution products (equations 34 and 35). Irradiation of anisole or benzonitrile with diethylamine gives the substitution product 7V,7V-diethylaniline (equations 36 and 37). Irradiation of benzylfluoride with diethylamine results in a side-chain substitution (equation 38). The photoreaction of p-fluorotoluene with diethylamine gives both substitution and reduction products (equation 39). 

The effect of steric hindrance was further studied by comparing the reactivity of primary and secondary amines of different steric requirements with 2,3,5,6-tetrachloronitro-benzene, 24 (Scheme 10)140. It is shown in Table 18 that open-chain amines give higher yield of the nitro-substitution products. 

While hydrosilylation of 1-alkenes and HSiCl3 with platinum catalysts provides linear products (1-trichlorosilylalkanes), palladium chloride modified with phosphines gives products carrying the trichlorosilyl group at the secondary carbon. This is highly remarkable because all other metal complexes studied so far lead to 1-substituted products. This regioselectivity leads to the possibility to carry out asymmetric hydrosilylation. 

However, when m-DNB was added to a solution of triphenylchloromethane and potassium tcrt-butylate in 2,2-dimethoxypropane, the yield of the substitution product and dimer of the triphenylmethyl radical markedly increased and decreased, respectively (Simig and Lempert 1979). Therefore, the main pathway of the reaction does not involve the ion-radical step. These authors suggested an alternative pathway, which is conformed by a thorough structural analysis of the secondary products formed along with tert-butyl ester of triphenylcarbinole (Huszthy et al. 1982a, 1982b) (Scheme 4.21). 

Kneen showed that a Wagner-Meerwein type rearrangement occurred on reaction of AuBrs(vp) with methanol and ethanol, the substituted product having a 6-membered ring system. Ionisation, rapid rearrangement of the primary carbonium ion to a more stable secondary, benzylic carbonium ion and subsequent attack by solvent can account for this reaction. 

Solid benzylic halogens are easily substituted with gaseous dialkylamines. Monoalkylamines are less suitable for uniform reactions due to secondary substitution of the initial product by the benzylic halide present. Some characteristic 100% yield conversions are listed in Scheme 31. The benzene (230) and naphthalene derivatives (231) started from the solid bromides, the anthracene derivatives (232) from the solid chlorides [22]. 

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