Halides secondary

All four mechanisms, 8 2 and E2 as well as 8 1 and El, are possible. The product composition is sensitive to the nucleophile (its strength as a nucleophile and as a base) and to the reaction conditions (solvent, temperature). In general, substitution is favored 

Chapter 6 Organic Halogen Compounds Substitution and Elimination Reactions 

Predict the product of the reaction of 1-bromo-l-methylcyclohexane with 

8ome of the above alkenes will also be formed by the El mechanism. 

PROBLEM 6.9 Draw structures for all possible elimination products obtainable from 2-chloro-2-methylpentane. 

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The reaction is applicable to primary and secondary halides only tertiary halides do not react. 

The preparation of esters can be classified into two main categories (1) carboxy-late activation with a good leaving group and (2) nucleophilic displacement of a carboxylate on an alkyl halide or sulfonate. The latter approach is generally not suitable for the preparation of esters if the halide or tosylate is sterically hindered, but there has been some success with simple secondary halides and tosylates (ROTs, DMF, K2CO3, 69-93% yield). ... 

Problem 11.12 i 3-Bromo-1-butene and l-bromo-2-butene undergo SN1 reaction at nearly the same rate even though one is a secondary halide and the other is primary. Explain. 

Alkylation reactions are subject to the same constraints that affect all Sn2 reactions (Section 11.3). Thus, the leaving group X in the alkylating agent R—X can be chloride, bromide, iodide, or tosylate. The alkyl group R should be primary or methyl, and preferably should be allylic or benzylic. Secondary halides react poorly, and tertiary halides don t react at all because a competing E2 elimination of HX occurs instead. Vinylic and aryl halides are also unreactive because backside approach is sterically prevented. 

As usual, tertiary substrates do not give the reaction at all but undergo preferential elimination. However, tertiary (but not primary or secondary) halides R3CCI can be converted to primary amines R3CNH2 by treatment with NCI3 and AlCl3 in a reaction related to 10-53. 

The reaction between primary and secondary halides and allyltributylstannane provides another method for unsymmetrical coupling RX + CH2=CHCH2 SnBu3 RCH2CH=CH2. ° ... 

This has also been accomplished with concentrated H2SO4 saturated with CO. Not surprisingly, only tertiary halides perform satisfactorily secondary halides give mostly rearrangement products. An analogous reaction takes place with alkanes possessing a tertiary hydrogen, for example. 

The method is quite useful for particularly active alkyl halides such as allylic, benzylic, and propargylic halides, and for a-halo ethers and esters, but is not very serviceable for ordinary primary and secondary halides. Tertiary halides do not give the reaction at all since, with respect to the halide, this is nucleophilic substitution and elimination predominates. The reaction can also be applied to activated aryl halides (such as 2,4-dinitrochlorobenzene see Chapter 13), to epoxides, " and to activated alkenes such as acrylonitrile. The latter is a Michael type reaction (p. 976) with respect to the alkene. 

Primary and secondary halides do not perform well, mostly because N-alkylation becomes important, particularly with enamines derived from aldehydes. An alternative method, which gives good yields of alkylation with primary and secondary halides, is alkylation of enamine salts, which are prepared by treating an imine with ethylmagnesium bromide in THF ... 

Route (a) is preferable since benzyllc bromides are reactive towards substitution and cannot eliminate whereas the secondary halide (11) in route (b) is relatively unreactive towards Sjj2 and can eliminate. 

Cyanide displacement is impossible on halide (14) and gives much elimination on secondary halide (13), The Grignard addition avoids these problems and gives high yields. ... 

Ansuer The Grignard method will be best for making (27) from secondary halide (28) as it avoids elimination reactions likely with cyanide ion. Disconnection (29a) now leads back to an alcohol (30) which can be made in a similar manner as (24). 

Annwer We should need keto-ester (17) for this, and even then alkylation with secondary halide (18) is iikely to be poor. Alternatively we could use nitrile (19) but this requires the same alkyl halide (IS). The Michael synthesis on page 133 is best. 

For now, let s consider the effect of the substrate on the rate of an El process. The rate is fonnd to be very sensitive to the nature of the starting aUcyl halide, with tertiary halides reacting more readily than secondary halides and primary halides generally do not nndergo El reactions. This trend is identical to the trend we saw for SnI reactions, and the reason for the trend is the same as well. Specihcally, the rate-determining step of the mechanism involves formation of a carbocation intermediate, so the rate of the reaction will be dependent on the stability of the carbocation (recall that tertiary carbocations are more stable than secondary carbocations). 

Reference has already been made (p. 82) to the fact that the reactions of some substrates, e.g. secondary halides, may follow a mixed first/second order rate equation. The question then arises whether such a reaction is proceeding via both SN2 and SN1 pathways simultaneously (their relative proportions depending on the solvent, etc.) or whether it is proceeding via some specific, in between mechanistic pathway. 

The reaction of alkyl halides with metal nitrites is one of the most important methods for the preparation of nitroalkanes. As a metal nitrite, silver nitrite (Victor-Meyer reaction), potassium nitrite, or sodium nitrite (Kornblum reaction) have been frequently used. The products are usually a mixture of nitroalkanes and alkyl nitrites, which are readily separated by distillation (Eq. 2.47). The synthesis of nitro compounds by this process is well documented in the reviews, and some typical cases are listed in Table 2.3.92a Primary and secondary alkyl iodides and bromides as well as sulfonate esters give the corresponding nitro compounds in 50-70% yields on treatment with NaN02 in DMF or DMSO. Some of them are described precisely in vol 4 of Organic Synthesis. For example, 1,4-dinitrobutane is prepared in 41 -46% yield by the reaction of 1,4-diiodobutane with silver nitrite in diethyl ether.92b 1-Nitrooctane is prepared by the reaction with silver nitrite in 75-80% yield. The reaction of silver nitrite with secondary halides gives yields of nitroalkanes of about 15%, whereas with tertiary halides the yields are 0-5%.92c Ethyl a-nitrobutyrate is prepared by the reaction of ethyl a-bromobutyrate in 68-75% yield with sodium nitrite in DMF.92d Sodium nitrite is considerably more soluble in DMSO than in DMF as a consequence, with DMSO, much more concentrated solutions can be employed and this makes shorter reaction times possible.926... 

The activation energy for an SnI reaction of a simple methyl, primary, or secondary halide is so large that, for all practical purposes, an SnI reaction does not compete with the corresponding Sn2 reaction. 

Secondary halide Can occur under solvolysis conditions in polar solvents Favored by good nucleophiles in polar aprotic solvents Can occur under solvolysis conditions in polar solvents Favored when strong bases are used... 

Haloalkanes are the most common substrates for the Michae-lis-Becker reaction.162-170 Of course, primary and benzylic halides provide more favorable reactions than secondary halides... 

In summary, primary halides react almost wholly by a bimolecular process and tertiary halides react by a unimolecular process. Secondary halides are structurally between these two extreme structural examples, since reaction occurs by both Sn2 and SnI routes. These two mechanisms proceed in competition, and occur concurrently. 

When following the (dual-route) reaction of a secondary halide with hydroxide ion, we find that the angle 9 through which plane polarized light is rotated will decrease, as for primary and tertiary halides, but will not reach zero at completion. In fact, the final angle will have a value between 0° and 6>finai because of the mixtures of products, itself a function of the mixture of SnI and Sn2 reaction pathways. 

The difficulty of distinguishing mechanisms at the ElcB-E2 borderline has also been discussed for reactions of secondary halides (1-X and 2-X) which feature a f-hydrogen made acidic by incorporation of an a-indenyl substituent (Scheme 1). 1,2-Elimination reactions of (/f,5 )-l-(l-X-ethyl)indene (1-X, X = Cl, Br, I, OBs) and the corresponding R,R isomers (2-X) promoted by water containing 25 vol.% acetonitrile... 

Tertiary halide Secondary halide Primary halide CHgX... 

Similarly, a primary alkyl halide will prefer a reaction, a secondary halide- 8, 2 or... 

II) CH3CH2CHCH3 Secondary halide reacts faster than tertiary halide. 

Tertiary halide reacts faster than secondary halide because of the greater stability of tert-carbocatlon. 

Catalysis by 18-crown-6 of the reaction of solid potassium cyanide with a variety of chlorides and bromides has been demonstrated.37 With primary bromides, yields are high and reaction times are 15-30 h at reflux in acetonitrile (83°C). Interestingly, the chlorides are more reactive and require reaction times of only 2h. Secondary halides react more slowly, and yields drop because of competing elimination. Tertiary halides do not react satisfactorily because elimination processes dominate. 

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