Substituted benzyl bromides

The inadmissibility of using any arbitrary reaction as a basis of comparison follows from the fact that in certain circumstances one and the same series of compounds may exhibit exactly opposite trends of the velocity of reaction with differing reagents. Thus, for example, those benzyl bromides substituted in the... 

Alkylation of aldol type educts, e.g., /3-hydroxy esters, using LDA and alkyl halides leads stereoselectively to erythro substitution. The erythro threo ratio of the products is of the order of 95 5. Allylic and benzylic bromides can also be used. The allyl groups can later be ozonolysed to gjve aldehydes, and many interesting oligofunctional products with two adjacent chiral centres become available from chiral aldol type educts (G. Prater, 1984 D. Seebach, 1984 see also M. Nakatsuka, 1990, p. 5586). 

Chiral oxazolines have also been utilized for the synthesis of ehiral ketones bearing quaternary earbon stereoeenters. As shown below, reaetion of substituted oxazoline 30 with 2 equiv PhLi followed by treatment with benzyl bromide gives ketone 33 upon aeidie hydrolysis. This reaetion is believed to proeeed via addition of PhLi to keteneimine 31 to afford metalated enamine 32, whieh undergoes alkylation at the nueleophilie earbon to provide 33 after aqueous workup. ... 

A three-necked flask may be used if magnetic stirring is substituted for mechanical stirring or if benzyl bromide is added with a syringe instead of a dropping funnel. 

However, Baker and Nathan ° observed that the rates of reaction with pyridine of p-substituted benzyl bromides (see Reaction 10-44) were about opposite that expected from electron release by the field effect. That is, the methyl-substituted compound reacted fastest and the tert-butyl-substituted compounded reacted slowest. 

Molar ratios of bromine to m-nitrotoluene ranging from 0.25 to 1.00 were applied. The reactants were contacted in an interdigital micro mixer followed by a capillary reactor. At temperatures of about 200°C nearly complete conversion is achieved (see Fig. 6). The selectivity to the target product benzyl bromide is reasonably high (at best being 85% at 200°C and higher being 80%). The main sideproduct formed is the nitro-substituted benzal bromide, i.e. the two-fold brominated side-chain product. 

For the delicate transesterification of a p-Lactam intermediate (for carbacephalosphorin skeleton), where originally hydrolysis of methyl ester was done homogeneously and then formation of the benzyl (or substituted benzyl) ester was done separately, Doecke et al. (1991) have devised a mild and efficient methodology using PTC. A dual use of a PT catalyst, Bu4NBr, in one pot was made in a CH2CI2 - H2O system. In the first step 5N NaOH was used, then the pH was adjusted to 7.2 to 7.8 and subsequently benzyl (or substituted benzyl) bromide was added. 

Route A 1- is very convenient for the substitution of OH groups by bromide or iodide. The reaction conditions are relatively mild (acetonitrile, room temperature, and reflux for 1—3 h, neutral medium). The activating halide (methyl iodide, ally or benzyl bromide) is added in excess (5 equivalents) or in large excess (10 equivalents) when the resultant halide is nearly as reactive as the activating halide. The imidazolium-iV-carboxylates are the important intermediates, which undergo a displacement reaction to give the halides,... 

It is clear that the ionizing power of the solvent used is important in many of these reductions. When 2,4,6-trimethylbenzyl chloride is heated with diphenylsi-lane in nitrobenzene at temperatures as high as 130°, no isodurene is formed.193 Not unexpectedly, the same lack of reactivity is reported for a series of benzyl fluorides, chlorides, and bromides substituted in the para position with nitro or methyl groups or hydrogen when they are heated in nitrobenzene solutions with triethylsilane, triethoxy silane, or diphenylsilane.193... 

The Michael-type reaction of an anion (generated from compound 77) with ethyl crotonate yielded the corresponding ester 78 in 82% yield (Scheme 19). Alkylation of compound 77 with benzyl bromide afforded derivative 79 in 85% yield. The attempted reactions of the anion with oxiranes and trimethylsilyl chloride did not lead to the expected substitution products and the starting oxadiazoles were recovered in 70-80% yields <2001ARK101>. 

Knochel demonstrated the effectiveness of soluble potassium or cesium alkoxides such as KO Bu or CsO Bu as well as KH in iV-methylpyrrolidinone (NMP) for promoting the 5-endo-dig cyclizations of 2-alkynylanilines to 2-substituted indoles in solution or the solid-phase <00AG(E)2488>. Alternatively, Cacchi coupled a palladium-catalyzed cyclization of o-alkynyltrifluoroacetanilides with the addition of benzyl bromide or ethyl iodoacetate to afford 2-substituted-3-benzyl or 3-indolylcarboxylate esters, respectively <00SL394>. Yamamoto reported a new palladium catalyzed indole synthesis in which 2-(l-alkynyl)-Ar-alkylideneanilines 117 give 2-substituted-3-(l-alkenyl)indoles 118 directly from the imine by the in situ coupling of an aldehyde with the alkynylaniline <00JA5662>. 

Synthesis of the amino-triazole derivative (43) was performed in the authors laboratory by Pati et al. [52] (Scheme 7). Substituted benzyl bromide was reacted with triphenylphosphine to produce the phosphonium bromide starting material, 44. The Wittig reagent, obtained by treatment with sodium hydride, was reacted with 3,4,5-trimethoxybenzaldehyde 18 to generate the nitro-stilbene 45 in good yields. The alkyne 46 was obtained by bromination of the stilbene, followed by didehydrobromination. Compound 46 was then reacted under thermal conditions with benzyl azides... 

The reactions of 3-pyrazolylaminomethylenemalonate (1478, R = R1 = R2 = H) with dimethyl sulfate, ethyl iodide, or benzyl bromide in boiling THF in the presence of sodium hydride yielded -substituted AK3-pyrazolyl)aminomethylenemalonates (1478, R = R1 = H, R2 = Me, Et, PhCH2). 3-Pyrazolylaminomethylenemalonate (1478, R = COOfBu, R1 = R2 = H) was dimethylated with methyl iodide in DMF in the presence of sodium methylate at room temperature overnight to give /V-methyl-N-U -dimethyl-S-pyrazolyDaminomethylenemalonate (1478, R = COOfBu, R1 = R2 = Me) in 88% yield (85JHC729). 

From Chapter 7 it is apparent that the trichloromethyl anion is formed under basic conditions from chloroform, as a precursor of the carbene. The anion can also react with Jt-deficient alkenes (see Section 7.3) and participate in nucleophilic substitution reactions, e.g. 1,1-diacyloxy compounds are converted into 1,1,1-trichloroalkan-2-ols [58] (Scheme 6.35). Similarly, benzyl bromides are converted into (2-bromoethynyl)arenes via an initial nucleophilic displacement followed by elimination of hydrogen bromide [59] (Scheme 6.35). 

Isoparametricity has been experimentally verified as occurring in the reactions of Y-substituted benzyl bromides with X-substituted anilines in dioxane and in 2, 3, and 5 m DMSO solutions in dioxane at 40 The phenomenon is interpreted on... 

Kinetic studies of various systems have been carried out as follows the reaction of 2,2 -dichlorodiethyl sulfide and of 2-chloroethyl ethyl sulfide with diethylenetriamine and triethylamine in 2-methoxyethanol ° the catalysed reactions of substituted phenols with epichlorohydrin the reactions of para-substituted benzyl bromides with isoquinoline under high pressure the reactions of O-alkylisoureas with OH-acidic compounds [the actual system was N, N -dicyclohexyl-0-(l-methylheptyl)isourea with acetic acid] and tlie ring opening of isatin in aqueous binary mixtures of methanol and acetonitrile cosol vents. 

A further attempt has been made to develop a predictive model for chirality transfer achieved through alkylation reactions of ester enolates which feature chiral auxiliaries. " Hippurate esters (30) derived from (lI , 25 )-trani-2-(p-substituted phenyl)cyclohexanols were found, on reaction with benzyl bromide, to give (31) with predominantly the S configuration at the alkylation centre but with no correlation between the degree of stereoselectivity (20-98%) and the electron density on the aromatic ring. 

The best compromise with respect to reactivity and availability of the starting material was the use of diisopropyl malate 107. This malic acid ester is easy to prepare and its alkylation with various benzyl bromides can be achieved with good yields (53-67%, not optimized) and high stereoselectivities (dr 95 5 for 120 and 121). An exception with respect to the stereoselectivity was the 2,4,6-trimethylbenzyl substituted succinate 122, which was obtained in a dr of only 83 17 (Fig. 6) [71]. 

The r] a-amino-organolithium species shown in Scheme 66 react with several different electrophiles at the y-position relative to the nitrogen atom. With benzyl bromide, electrophilic substitution is invertive, but with enones and ketones, it is retentive (Scheme 67). Reversal of steric course between CO2 (Sg2inv) and ClC02Me (Sg2ret) is also observed in this system (compare Scheme 64). Hydrolysis of the enamine products affords /3-substituted aldehydes that can be further elaborated. " ... 

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