Benzyl bromide hydrolysis

Solvent Preparation. The most critical aspect of the solvent is that it must be dry (less than 0.02 wt % of H2O) and free of O2. If the H2O content is above 0.02 wt %, then the reaction of Mg and RX does not initiate, except for an extremely reactive RX species, such as benzyl bromide. Although adventitious O2 does not retard the initiation process, the O2 reacts with the Grignard reagent to form a RMg02X species. Furthermore, upon hydrolysis, the oxidized Grignard reagent forms a ROH species that may cause purification problems. 

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. ... 

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. 

The asymmetric reduction of the benzoxathiin is very appealing because of its simplicity (Scheme 5.3). It was envisioned that intermediate 16 could be prepared from thiol-phenol 7 and bro moke tone 17. Scheme 5.8 summarized the synthesis for 16. The l,3-benzoxathiol-2-one 35 was prepared from 1,4-benzoquinone and thiourea following a literature procedure with minor modifications. Benzylation of 35 with benzyl bromide in the presence of KI gave benzyl ether 36 as a crystalline solid. It was observed that the benzylation gave better results when the reaction was run under anaerobic conditions. Hydrolysis of thiocarbonate 36 gave free thiophenol 7 which was used directly in the next reaction. 

The chiral A/ -propionyl-2-oxazolidones (32 and 38) are also useful chiral auxiliaries in the enantioselective a-alkylation of carbonyl compounds, and it is interesting to observe that the sense of chirality transfer in the lithium enolate alkylation is opposite to that observed in the aldol condensation with boron enolates. Thus, whereas the lithium enolate of 37 (see Scheme 9.13) reacts with benzyl bromide to give predominantly the (2/ )-isomer 43a (ratio 43a 43b = 99.2 0.8), the dibutylboron enolate reacts with benzaldehyde to give the (3R, 25) aldol 44a (ratio 44a 44b = 99.7 0.3). The resultant (2R) and (25)-3-phenylpropionic acid derivatives obtained from the hydrolysis of the corresponding oxazolidinones indicated the compounds to be optically pure substances. 

The selective alkylation of a chemically distinct phenohc site on a perfluorinated aromatic has been achieved following a polymer assisted solution phase protection of an alternative o-hydroxybenzoic acid unit as the dioxin-4-one (19) (Scheme 2.45) [66]. A diverse set of 22 different alkyl and benzyl bromides were then attached to the free phenol using cesium fluoride as the base, followed by treatment with Amberlyst 15 and Amberlyst A-21 as the work-up. Subsequent hydrolysis of the dioxin-4-one group with NaOH proceeded smoothly and was quenched... 

Since ketone R)-16 was prepared in a non-selective way when an achiral imino enolate was alkylated, it was considered whether alkylation of chiral enolates, such as that of oxazoline 18, with benzyl bromide 14, would provide stereoselective access to the corresponding alkylation product 19 with R-configuration at C(8) (Scheme 4). Indeed, alkylation of 18 with 14 gave the biaryl 19 and its diastereoisomer almost quantitatively, in a 14 1 ratio. However, reductive hydrolysis using the sequence 1. MeOTf, 2. NaBH4, and 3. H30", afforded hydroxy aldehyde 20 in 25% yield at best. Furthermore, partial epimerization at C(8) occurred (dr 7.7 1). An alternative route, using chiral hydrazones, was even less successful. 

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. " ... 

Miki and Hachiken reported a total synthesis of murrayaquinone A (107) using 4-benzyl-l-ferf-butyldimethylsiloxy-4fT-furo[3,4-f>]indole (854) as an indolo-2,3-quinodimethane equivalent for the Diels-Alder reaction with methyl acrylate (624). 4-Benzyl-3,4-dihydro-lfT-furo[3,4-f>]indol-l-one (853), the precursor for the 4H-furo[3,4-f>]indole (854), was prepared in five steps and 30% overall yield starting from dimethyl indole-2,3-dicarboxylate (851). Alkaline hydrolysis of 851 followed by N-benzylation of the dicarboxylic acid with benzyl bromide and sodium hydride in DMF, and treatment of the corresponding l-benzylindole-2,3-dicarboxylic acid with trifluoroacetic anhydride (TFAA) gave the anhydride 852. Reduction of 852 with sodium borohydride, followed by lactonization of the intermediate 2-hydroxy-methylindole-3-carboxylic acid with l-methyl-2-chloropyridinium iodide, led to the lactone 853. The lactone 853 was transformed to 4-benzyl-l-ferf-butyldimethylsiloxy-4H-furo[3,4- 7]indole 854 by a base-induced silylation. Without isolation, the... 

Reduction of the complex on Raney nickel yielded benzylamine, N-methyl-benzylamine, and N,N-dimethylbenzylamine but no / -phenylbenzylamine, a reduction product resulting under the same reaction conditions from benzyl cyanide. Hydrolysis with dilute sulfuric acid in acetic acid yielded benzylamine only, and oxidation of the complex with potassium permanganate gave 4.2 moles of benzoic acid per mole of complex. The bromide anion can be exchanged metathetically with various other anions such as perchlorate, iodide, and thiocyanate. When heated at 100° C. in vacuum, the complex lost one mole of benzyl bromide and yielded only one dicyanotetrakis(benzylisonitrile)iron(II) complex. 

Other syrupy, benzylated bromides bearing O-acetyl or O-p-nitro-benzoyl groups were also prepared and characterized,86-84 as well as a partially benzylated chloride.85 Acid hydrolysis of 22 gave crystalline 2-O-benzyl-a-L-fucose, which was acylated with p-nitrobenzoyl chloride-pyridine. Treatment84 of the resulting tris(p-nitrobenzoate) with hydrogen bromide-dichloromethane led to precipitation of p-nitrobenzoic acid and formation of syrupy 2-0-benzyl-3,4-di-0-(p-nitro-benzoyl)-a-L-fucopyranosyl bromide (33). 

Cyclization of side chain nitriles has found extensive use in the synthesis of benzocyclobutenes (70 n = 2),104 the versatile synthons which open on mild thermolysis to give o-quinodimethanes for inter- and intra-molecular [4 + 2] trapping.108 The nitrile group in (70) can be manipulated into a variety of functionalities for appending the dienophile portion. For example, in the synthesis of chelidonine, the nitrile (71) was converted, by hydrolysis followed by Curtius degradation and reaction of the formed isocyanate with benzyl alcohol, to a urethane (72). The latter was then condensed with a benzyl bromide to get the compound (73), which was elaborated further as shown in Scheme 14.109... 

The rate of hydrolysis of the disilanyl benzyl bromide 28 is about 1 x 105 larger than that of 2953. Thus the -effect of 28 is similar in magnitude to 26. 

O-Benzylation of 148 with benzyl bromide in the usual manner yielded the tri-0-benzyl derivative (149), [a]p7 —0.8° (chloroform). On hydrolysis with aqueous acetic acid, 149 gave the compound (150), which was further converted to the compound (151) by sodium borohydride reduction. Periodic acid oxidation of 151 and successive sodium borohydride reduction gave 5,6-di-<9-acetyl-2,3,4-tri-0-benzyl-pseudo-a-L-altropyranose (152), [a] 6 —25.7° (chloroform), after conventional acetylation. Reductive cleavage of 152 with sodium in liquid ammonia and subsequent acetylation afforded pseudo-a-L-altropyranose pentaacetate (153), m.p. 84-85 °C, [ ]q6 —13.7° (chloroform). Hydrolysis of 153 gave 154, [ot] —43.6° (methanol) [35] (Scheme 24). 

Hydrolysis of the benzylic bromide gives the corresponding benzylic alcohol. The bromine that is directly attached to the naphthalene ring does not react under these conditions. 

In the first step illustrated in Scheme 69, the carboxylic acid ethyl ester 241 undergoes quantitative solvolysis, using NaOEt 237 (30mol%), the resulting naphthol derivative 242 was subsequently protected as its benzyl ether 244 using aq. NaOH 26 and benzyl bromide 46 to afford ethyl-4-(benzyloxy)-2-naphthoate 243 in 72% yield. Quantitative hydrolysis of the ethyl ester 243 followed, using aq. NaOH 26 at 68 °C for 48 min. The carboxylic acid 244 was used directly with the Shioiri-Yamada reagent... 

Schiff base 52 in one-pot under mild phase-transfer conditions. For example, the initial treatment of a toluene solution of 52 and (S,S)-32e (1 mol%) with allyl bromide (1 equiv.) and CsOHH20 at —10 °C, and the subsequent reaction with benzyl bromide (1.2 equiv.) at 0 °C, resulted in formation of the double alkylation product 53 in 80% yield with 98% ee after hydrolysis. Notably, in the double alkylation of 52 by the addition of the halides in reverse order, the absolute configuration of the product 53 was confirmed to be opposite, indicating intervention of the chiral ammonium enolate 54 at the second alkylation stage (Scheme 4.17) [50]. 

For GC analysis, the salts of the lowest molecular weight acids present in ozonation products subjected to base-promoted hydrolysis have been converted to their benzyl esters by reaction with benzyl bromide (Bonnet et al. 1989). The salts of all acids produced have commonly been converted to the free acids, usually with the aid of a cation exchange resin. The acids have then been converted to methyl esters by reaction with diazomethane (Bonnet et al. 1989) or, more often, have been converted to trimethylsilyl (TMS) esters (Matsumoto et al. 1986, Taneda et al. 1989, Habu et al. 1990). Trimethylsilylation has the major advantage that alcoholic and phenolic hydroxyl groups are simultaneously converted to TMS ethers, thus greatly facilitating GC analysis. 

The alcohol product can be formed by reduction of a carboxylic acid with UAIH4. The carboxylic acid can be synthesized either by Grignard carboxylation or by nitrile hydrolysis. The product can also be formed by a Grignard reaction between benzyl bromide and formaldehyde. 

A synthesis of 4-hydroxy-substituted TIQ has been developed in connection with plant isoquinolines (169,170), and the glycine ester route used for a similar purpose (171) is shown in Fig. 23. Reaction of the benzyl bromide 85 with N-methylglycine ester gave 86 the ketoester 87 was obtained on Dieckmann condensation. Alkaline hydrolysis of ester 87 followed by treatment with mineral acid gave ketone 88 alcohol 89 was obtained on reduction of 88 with sodium borohydride. 

Stereoselective Alkylation. Chiral tricyclic lactams can be prepared from (l/ ,2/ ,35,5/ )-ATBH and y-keto acids by heating in toluene with a catalytic amount of p-toluenesulfonic acid (eq 7). Enolization of the resulting lactams with sec-butyllithium, followed by trapping with methyl iodide, furnishes the methylated products in high diastereoselectivity. Subsequent enolization and alkylation with benzyl bromide affords a single diastereomer in 82% yield. Further acidic hydrolysis in butanol provides the desired ester with a quaternary asymmetric center (eq 7). ... 

When copper or iron strips were placed in water after long exposure to benzyl bromide vapors, they showed much greater dissolution than unexposed strips (Table IV) (97). Replacement of water by deuterium oxide as the reaction medium yielded CHjD as the primary gaseous products (97). While this would arise from the hydrolysis of a metal-methyl bond ... 

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