Dimethoxybenzyl bromide

Solubility reactions are usually earned out in polar solvents such as THF or DMF. 

Preparative Methods synthesized from commercially available 3,4-dimethoxybenzyl alcohol and PBrs or HBr.  

Handling, Storage, and Precautions the reagent is quite unstable and is best prepared fresh or stored at low temperature under nitrogen. It is a laehrymator. 

DDQ oxidation under anhydrous conditions, and further oxidized to base cleavable benzoates. Simple benzyl ethers and many other protecting and functional groups remain unaffected under these conditions.  

Each substituted benzyl ether has a different oxidation potential (1.45 V for the DMB-OR, and 1.78 V for the PMB-OR), so each methoxy substitution pattern results in different rates of ether cleavage. This means that the DMB group can be removed in the presence of a PMB ether with high selectivity (eq 3). It has also been shown that other methoxybenzyl ethers react at widely differing rates. For example, the reaction time for the DMB ether was 20 min (86% yield of alcohol), and the 2,6-dimethoxy isomer required 27.5 h (80% yield) (eq 4). Other substitution patterns give reaction times between these two extremes. 

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Menthyl isocyanopropanoate (5) has been alkylated by means of sodium hydride in tetrahydrofuran and subsequent addition of 3,4-dimethoxybenzyl bromide to give the product 6 in high yield115. The latter was transformed into a-methyl-(3,4-dimethoxy)benzylalanine hydrochloride (7, 85% overall yield from the propanoate) [a] 0 —0.8° (c = 7.5, CH3OH) mp 162-165 °C (decomp). The optically pure form has [a]p7 —8.8° (c = 0.84, CH3OH) and mp 169-171 °C (decomp). 

Boc protection of the amine, complexation with hexacarbonylchromium, and then amine deprotection with neat formic acid provides (R)-( + )-halostachine(tricarbonyl)chromium(0) (57). Treatment of 57 with 3,4-dimethoxybenzyl bromide in dichloromethane affords in 36% yield (i )-( + )-tricarbonyl f -2-[3,4-dimethoxybenzyl(methyl)amino]-l-phenylethanol -chromium(O) (58), which undergoes a highly selective acid-promoted cyclization that proceeds with retention of configuration to yield, after decomplexation, optically pure (R)-(-h)-6,7-dimethoxy-2-methyl-4-phenyl-l,2,3,4-tetrahydroisoquinoline (59) in moderate yield (Scheme 11) [13]. 

Related Reagents. Benzyl Chloride Benzyl Iodide Benzyl p-Toluenesulfonate Benzyl 2,2,2-Triehloroacetimidate Benzyl Trifluoromethanesulfonate 3,4-Dimethoxybenzyl Bromide p-Methoxybenzyl Chloride 4-Methoxybenzyl 2,2,2-Triehloroacetimidate. 

Trichloroacetimidate 3,4-Dimethoxybenzyl Bromide (p-Methoxybenzyloxy)methyl Chloride 4-Methoxybenzyl... 

Aust. J. Chem. 26,799(1973) gives a 2 step synthesis of 5-alkylresorcinols by condensation of beta-ketosulphones with 3,5-dimethoxybenzyl bromide and then reduction. Aust. J. Chem. 26,183(1973) gives a synthesis from 3,5-dimethoxy-N,N-dimeth-ylbenzylamine in 7 steps (but perhaps only 4 will reach a cpd. that can give an active THC analog). 

The oxidation of bromide by hydrogen peroxide is a two-electron process that results in electrophilic bromination of organic substrates as opposed to radical bromination. This reactivity was established from the products of bromination of 2,3-dimethoxytoluene in which ring-substituted bromo-2,3-dimethoxytoluene is the sole product (26). The product of bromination by bromine radical, 2,3-dimethoxybenzyl bromide (27), was not observed. 

Persoonol dimethyl ether, the 3(Z)-alkene from Persoona elliptica has been synthesised (ref. 37) from 3,5-dimethoxybenzyl bromide by way of 4-(3,5-dimethoxyphenyl)but-1-yne which was alkylated with n-heptyl 4-toluenesulphonate followed by final reduction of the all ne product as shown in the scheme This method of preparation of the butyne was probably obligatory because of the inapplicability of the alkylation technique with 2-(3,5-dimethoxyphenyl)ethyl bromide due to its facile dehydrobromination. 

The efficient synthesis of [ F fluoro-L-Dopa (80) was reported by Lemaire et al. [53] [ F]fluoro-L-Dopa (80), a radiopharmaceutical for positron emission tomography (PET), was synthesized by asymmetric PT-catalyzed alkylation of 14 with 2-[ F]fluoro-4,5-dimethoxybenzyl bromide 81. An excess of the catalyst was employed in the key step of this reaction to give key intermediate 82 in veiy short time with high yield and enantioselectivity followed by a final very fast hydrolysis to give [ F] fluoro-L-Dopa (80) to be readily used for PET diagnostics (Scheme 15). 

Reduce 3,5-dimethoxybenzoic acid with lithium aluminum hydride to 3,5-dimethoxybenzyl alcohol (I), to 10.5 g (I) in 100 ml methylene chloride at 0° C add 15 g PBr3 warm to room temperature and stir for one hour. Add a little ice water and then more methylene chloride. Separate and then dry, evaporate in vacuum the methylene chloride. Add petroleum ether to precipitate about 11.5 g of the benzyl bromide (II). To 9.25 g (II), 15 g Cul, 800 ml ether at 0° C, add butyl (or other alkyl)-Li (16% in hexane), and stir for four hours at 0° C. Add saturated NH4C1 and extract with ether. Dry and evaporate in vacuum the ether (can distill 100/0.001) to get about 4.5 g olivetol dimethyl ether (HI) or analog. Distill water from a mixture of 90 ml pyridine, 100 ml concentrated HC1 until temperature is 210° C. Cool to 140 0 C and add 4.4 g (III) reflux two hours under N2. Cool and pour into water. Extract with ether and wash with NaHC03. Make pH 7 and dry, evaporate in vacuum to get 3.8 g olivetol which can be chromatographed on 200 g silica gel (elute with CHC13) or distill (130/0.001) to purify. 

Olivetol. 3,5-Dimethoxybenzyl alcohol. (This can be made by reducing 3,5-dimethoxybenzoic acid, or it can be purchased.) (10 g) in 100 ml of methylene chloride is cooled to 0° and 15 g of PBrs is added. Warm to room temp and stir for 1 hour, then add a little ice water followed by more methylene chloride. Add petroleum ether to precipitate the benzyl bromide, which is separated off. 9.3 g of the benzyl bromide is put in a flask with 800 ml of dry ether and then add 15 g of copper iodine at 0°. Add butyl lithium (16% in hexane) and stir for four hours at 0°. Add saturated NH4CI and extract with ether. The ether is removed by evaporating in vacuo to give the olivetol dimethyl ether which must be demethylated by one of the methods given in the above formulas. Yield A little over 4 g. Taken from HCA, 52, 1132. 

Cationic surfactants with an electron rich phenyl substituent on the hydrophilic ammonium head group (phenyl, 2,4-dimethoxyphenyl, and 2,4-dimethoxybenzyl dimethylammonium bromides) were found to be more efficient catalysts than CTAB for the hydrolysis of 2,4- and 2,6-dinitrophenyl phosphates (Bunton et al., 1970). The pseudo-first order rate constants increased appreciably at low concentrations of these... 

Condensation of 1 with 3,4-dimethoxybenzyl cyanide afforded the epimeric cyano alcohols 2, which on alkaline hydrolysis gave the epimeric y -lactones 3 in 64% yield. Treatment of 3 with crotyl bromide afforded the a,a-disubstituted lactone 4. Acid-catalyzed debenzy-lation of 4 afforded the alcohol 5, which on sequential saponification, periodate cleavage and reduction gave the lactone 7 via 6. Palladium-catalyzed oxidation of 7 afforded 8, which underwent intramolecular cyclization to produce 9 in 66% yield. Treatment of 9 with methylamine gave 10 (41%) and 11 (7%) however, the former can be cyclized into the latter in 85% yield. Reduction of 11 furnished 12 in 77% yield. 

Acylation and alkylation reactions are illustrated in the following examples. Two modes of cyclisation of 2-(3,4-dimethoxybenzyl)-3-phenylpropionic acid in dichloromethane, after conversion to the acid chloride, have been described by reaction with oxalyl chloride in dimethylformamide during 12 hours (ref.81). After cooling of the starting solution to -15°C, aluminium bromide (in 100mole% proportion) in dichloromethane for 24 hours gave... 

Related Reagents. Benzyl Bromide Benzyl Chloride Benzyl Iodide Benzyl Trifluoromethanesulfonate 3,4-Dimethoxybenzyl... 

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