2- Bromobutane alkylation with

As actually carried out and reported in the chemical literature diethyl malonate has been alkylated with 2 bromobutane in 83-84% yield and the product of that reaction converted to 3 methylpentanoic acid by saponification acidification and decarboxylatlon in 62-65% yield j... 

DF 0.09, 10% cross-linked gel polystyrene, the enolate generated with triphenyl-methylUthium at room temperature and trapped as soon as the red color of Ae base faded, gave 94-97% GC yields from acylation with p-nitrobenzoyl chloride or acetyl chloride and from alkylation with 1-bromobutane or benzyl bromide. Isolated yields were 73-87% on a 16-34 mmol scale, and 77% in one example on a 100 mmol scale (175 g of dry polymeric reagent). TTie polymer was recycled with no decrease in acylation yield. The analogous benzyl ester in solution gave 59% self[Pg.273]

B. Kinetics of Reaction with Alkyl Halides (14). Prior to the work of Danen and Warner, (14,15) few rate constants for the reaction of O2 with alkyl halides had been reported. In an electrochemical study, Merritt and Sawyer (16) had determined the pseudo-first-order rate constants at 28 C for three butyl chlorides in DMSO solvent. In a similar manner, Dietz, et al., (J) had reported a pseudo-first-order rate constant for 1-bromobutane reacting with electrogenerated O2 in DMF containing tetra-n-butylammonium perchlorate. San Filippo and coworkers (S) had determined the relative reactivity of several alkyl halides but had not reported any absolute rate constants. 

We see that a secondary alkyl halide is needed as the alkylating agent The anion of diethyl malonate is a weaker base than ethoxide ion and reacts with secondary alkyl halides by substitution rather than elimination Thus the synthesis of 3 methylpentanoic acid begins with the alkylation of the anion of diethyl mal onate by 2 bromobutane... 

Alkyne alkylation is not limited to acetylene itself. Any terminal alkyne can be converted into its corresponding anion and then alkylated by treatment with an alkyl halide, yielding an internal alkyne. For example, conversion of 1-hexyne into its anion, followed by reaction with 1-bromobutane, yields 5-decyne. 

Silver fluoborate, reaction with ethyl bromide in ether, 46, 114 Silver nitrate, complexing with phenyl-acetylene, 46, 40 Silver oxide, 46, 83 Silver thiocyanate, 45, 71 Sodium amide, in alkylation of ethyl phenylacetate w ith (2-bromo-ethyl)benzene, 47, 72 in condensation of 2,4-pentanedione and 1 bromobutane to give 2,4-nonanedione, 47, 92 Sodium 2 ammobenzenesulfinate, from reduction of 2 mtrobenzenesul-finic acid, 47, 5... 

The formation of 2-bromoethylsulfonate followed the method described in "Organic Syntheses" (21). In the attempt to generalize this reaction, we noted that neither 1,3-dibromopropane nor 1,4-di-bromobutane was miscible in the ethanol-water reaction solvent. Directly following the described procedure did produce both the 3-bromopropylsulfonate and 4-bromobutylsulfonate, but in low yields of roughly 20%. Improved procedures for alkylation were developed using acetonitrile as the solvent. The yields of the reactions for both III and IV with the ethyl, propyl, and butyl bromosulfonates are given in the "Experimental section. 

In the first systematic study on nucleophilic substitutions of chiral halides by Group IV metal anions, Jensen and Davis showed that (S )-2-bromobutane is converted to the (R)-2-triphenylmetal product with predominant inversion at the carbon center (Table 5)37. Replacement of the phenyl substituents by alkyl groups was possible through sequential brominolysis and reaction of the derived stannyl bromides with a Grignard reagent (equation 16). Subsequently, Pereyre and coworkers employed the foregoing Grignard sequence to prepare several trialkyl(s-butyl)stannanes (equation 17)38. They also developed an alternative synthesis of more hindered trialkyl derivatives (equation 18). 

The characteristics of homogeneous crown-ether catalysis were nicely demonstrated by Thomassen et al. (1971) who studied the rate of alkylation of potassium phenoxide with 1-bromobutane in dioxan at 25°C. By measuring the initial consumption of phenoxide (r, in M s-1), any effect of the bromide ion was neglected. The results (Table 21) show hardly any effect of tetraglyme... 

The effect of crown ethers on the geometrical orientation in base-promoted E2 eliminations has been studied by several groups. Bartsch et al. (1973) have investigated the effect of several parameters on the potassium alkoxide-promoted eliminations of HBr from 2-bromobutane (Table 45). In the absence of crown ethers the relative amount of 1-butene formed increases, while the trans/cis ratio of the 2-butenes decreases, with decreasing solvent polarity. Furthermore, the proportion of 1-butene increases and the trans/cis ratio decreases on increasing the base concentration. These effects were explained in terms of steric interactions between the base and a- and /7-alkyl groups in the... 

In contrast with the amides, which yield only A-alkylated products, the corresponding reaction of 5,5-dimethylisoxazolidin-3-one (Scheme 5.8) produces both the /V-and 0-alkylated derivatives [24] (Table 5.15). With the exception of the sec-bromobutane, the overall yields from primary and secondary haloalkanes are comparable, but there is a tendency for the secondary haloalkanes to produce slightly higher yields of the ethers. 

ControUed-potential oxidations of a number of primary, secondary, and tertiary alkyl bromides at platinum electrodes in acetonitrile have been investigated [10]. For compounds such as 2-bromopropane, 2-bromobutane, tert-butyl bromide, and neopentyl bromide, a single Ai-alkylacetamide is produced. On the other hand, for 1-bromobutane, 1-bromopentane, 1-bromohexane, 1-bromo-3-methylbutane, and 3-bromohexane, a mixture of amides arises. It was proposed that one electron is removed from each molecule of starting material and that the resulting cation radical (RBr+ ) decomposes to yield a carbocation (R" "). Once formed, the carbocation can react (either directly or after rearrangement) with acetonitrile eventually to form an Al-alkylacetamide, as described above for alkyl iodides. In later work, Becker [11] studied the oxidation of 1-bromoalkanes ranging from methyl to heptyl bromide. He observed that, as the carbon-chain length is increased, the coulombic yield of amides decreases as the number of different amides increases. 

Sodium amide, in alkylation, of di-phenylmethane, 48, 80 of ethyl phenylacetate with (2-bromoethyl)benzene, 47, 72 in condensation of 2,4-pentanedione and 1-bromobutane to give 2,4-nonanedione, 47, 92... 

It has been shown that a complete shift in stereochemistry of the nucleophilic reactions of (29), with alkyl halides such as 2-bromobutane or cis-2-bromomethoxycyclohexane, from racemization to complete inversion, is induced by increase in the inner-sphere stabilization of the transition state from 0 to 3 kcal mol" This has been ascribed to competition between inner-sphere 5)vr2 and outer-sphere electron-transfer processes the former being extremely sensitive towards inner-sphere stabilization. 

Korneev and Kaufmann successfully lithiated 2-bromo-l,l-diphenylethylene (46) by bromide-lithium exchange to form 2-lithio-l,l-diphenylethylene (47). A second lithia-tion could be effected in four hours at room temperature by deprotonation of the aromatic ring with w-butyllithium in the presence of TMEDA (Scheme 17). Like in the synthesis of compound 23, the first lithiation activates the ortho-hydrogen atom of the Z-phenyl substituent to give 1,4-dilithium compound 48. In total, three equivalents of the alkyl-lithium base are required the third equivalent is consumed in the trapping reaction of w-bromobutane with generation of octane. 

Effects of polymer structure on reaction of phenylacetonitrile with excess 1-bromo-butane and 50% NaOH have been studied under conditions of constant particle size and 500 rpm stirring to prevent mass transfer limitations I03). All experiments used benzyltrimethylammonium ion catalysts 2 and addition of phenylacetonitrile before addition of 1-bromobutane as described earlier. With 16-17% RS the rate constant with a 10 % CL polymer was 0.033 times that with a 2 % CL polymer. Comparisons of 2 % CL catalysts with different % RS and Amberlyst macroporous ion exchange resins are in Table 6. The catalysts with at least 40% RS were more active that with 16 % RS, opposite to the relative activities in most nucleophilic displacement reactions. If the macroporous ion exchange resins were available in small particle sizes, they might be the most active catalysts available for alkylation of phenylacetonitrile. 

When the reactions of alkyl bromides (n-Q-Cg) with phenoxide were carried out in the presence of cosolvent catalyst 51 (n = 1 or 2,17 % RS) under triphase conditions without stirring, rates increased with decreased chain length of the alkyl halide 82). The substrate selectivity between 1-bromobutane and 1-bromooctane approached 60-fold. Lesser selectivity was observed for polymer-supported HMPA analogue 44 (5-fold), whereas the selectivity was only 1,4-fold for polymer-supported phosphonium ion catalyst 1. This large substrate selectivity was suggested to arise from differences in the effective concentration of the substrates at the active sites. In practice, absorption data showed that polymer-supported polyethylene glycol) 51 and HMPA analogues 44 absorbed 1-bromobutane in preference to 1-bromooctane (6-7 % excess), while polymer-supported phosphonium ion catalyst 1 absorbed both bromides to nearly the same extent. 

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