1-Bromopentane, reaction with nucleophiles

There are two major reactions of enolates (1) displacement reactions with alkyl halides or other suitable electrophiles and (2) nucleophilic addition to carbonyl compounds. Reaction of 58 with butanal to give 59 and reaction of 61 with bromopentane to give 62 are simple examples of each process. Enolate anions function as carbon nucleophiles and their reactions are fundamentally the same as those discussed in Section 8.3.C for acetylides. Although there are interesting differences, treating an enolate anion as a carbon nucleophile is very reasonable. 

Apart from HCl, HBr, and HI, there are certainly other strong mineral acids, including nitric acid (HNOg pK = -1.3), sulfuric acid (H2SO4 pK = -5.2), and perchloric acid (HCIO4 pK = -4.8). If 1-pentene reacts with any of these acids, the product will be the secondary cation, 16, but the nucleophilic counter-ion changes. When HBr reacts with 1-pentene, the counter-ion is bromide (Br ), which is rather nucleophilic, and the product is 2-bromopentane. However, if nitric acid reacts, the nucleophile is the nitrate anion (NOg"), which is resonance stabilized and is less likely to donate electrons (less nucleophilic). The product of a reaction with nitric acid in which the nitrate anion reacts as a nucleophile with 16 is 17. When 1-pentene reacts with sulfuric acid, the... 

The ether is prepared via the corresponding halide. If the C-0 bond in 163 is disconnected, the logical bond polarization makes O 6- and a donor site Cj, and that of C2 is 6+, or (an acceptor site). In Chapter 25, Table 25.1 indicates that a synthetic equivalent for Cg is an alkyl halide. Therefore, a reasonable disconnection of 163 leads to 2-bromopentane (167) and the nucleophilic methoxide ion. This suggests a Williamson ether synthesis (Section 11.3.2). Can 167 be prepared directly from 1-pentene The answer is yes, by reaction of the alkene with HBr (Chapter 10, Section 10.2). Therefore, the retrosynthesis shown leads to the synthesis shown in which 1-pentene reacts with HBr to give 167, and a subsequent Sn2 reaction with... 

Cyanide is a bidentate nucleophile. Draw the product that results from a reaction with 1-bromopentane where carbon is the nucleophile. Draw the product that results from the reaction where nitrogen is the nucleophile. Calculate the formal charge, if any, on both products. Assuming there is a mixture of these two products, suggest a simple way that you might separate them. 

Primary halides, such as 1-bromopentane (15) usually give very poor yields of an alkene when treated with KOH in ethanol. Based on experimental results with primary alkyl halides, assume that primary alkyl halides do not give an alkene under normal E2 conditions. The activation energy required to generate a transition state such as 16 (for an E2 reaction of 15) is so high that the E2 reaction is quite slow relative to another reaction such as substitution. It is not impossible, just slow. Remember that hydroxide and ethoxide are nucleophiles as well as bases, and one can imagine a facile Sn2 reaction at the primary carbon, which is faster than the E2 reaction. If any reaction occurs when 15 reacts with hydroxide in ethanol, it will likely be the 8 2 product, 1-pentanol via reaction with hydroxide, or 1-ethoxypentane via reaction with ethoxide. If any alkene is formed, it is usually a very minor product. 

Table I. Reaction of 1-Bromopentane with Various Nucleophiles under PTC Conditions ...

At first, this transformation might seem challenging, since no reaction exists that adds an alkynyl group to an alkene. However, a systematic approach to these problems always begins with the ending a retrosynthesis of the desired product. Once the alkyne TM is disconnected to give an acetylide nucleophile and a five-carbon electrophile (1-bromopentane), the solution becomes clear. 

Problem 9.10 The rates of Sj 2 reactions of primary haloalkanes can differ substantially. The rate of reaction of 1-bromopentane with a nucleophile is approximately 4 x 10 times faster than the reaction of 2,2 dimethyl-l-bromopropane. Explain why. 

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