P-methoxybenzyl alcohol

Problem 17.5 p-Nitrobenzyl alcohol is more acidic than benzyl alcohol but p-methoxybenzyl alcohol is less acidic. Explain. 

Reduction ofp-methoxybenzaldehyde, typical procedure method A To lithium phenyltel-lurolate prepared from PhLi (2.1 M, 4 8 mL, 10 mmol) and Te (1.27 g, 10 mmol) in THF (30 mL) under Nj is added p-methoxybenzaldehyde (0.272 g, 2 mmol) at -78°C followed by TFA (0.77 mL, 10 mmol). The solution is stirred for a further 2 h, and allowed to warm at room temperature. H O (200 mL) is added and the product is extracted with ether. The extract is dried (Na2S04), evaporated and the residue separated by SiOj chromatography from the formed diphenyl ditellnride, giving p-methoxybenzyl alcohol (0.23 g (93%)). 

The free base 13 is obtained by stirring with sodium acetate in MTBE. Benzylation by treatment with a mild acid and p-methoxybenzyl alcohol provides 14 (Emert et al., 1977 Henneus et al., 1996). The initial conditions for the asymmetric addition of the lithium acetylide to the trifluoroketone appear in an earlier Merck paper (Thompson et al., 1993, 1996). Optimization of these conditions, which include some elaborate NMR studies (Thompson et al., 1998) and key scale-up experiments, provides a reliable and scaleable procedure to install the stereocenter in high yield, purity, and enantioselectivity (Scheme 6.3). n-Butyllithium (or w-hexyllithium, minimum four equivalents) is added to a solution of (lR,25)-A-pyrrolidinylnorephedrine (Corey and Cimrich, 1994) (two equivalents) and cyclopropylacetylene (two equivalents) at — 10°C and the reaction is allowed to warm to 0°C. These conditions are critical to establish the chiral complex that is responsible for the high enantioselectivity. This solution is cooled below — 50°C, and trifluoroketone 14 in THE is added and stirred for about 1 h at this temperature before... 

A third step causes the lithium salt of p methoxybenzyl alcohol 14 to be subjected to the same region sequence as the two previous reagents. 

This is a solvolysis reaction that proceeds in two steps. The first step involved protonation of the hydroxy group of p-methoxybenzyl alcohol. Once protonated, a bromide ion displaces water, generating the illustrated product. The reaction shown below demonstrates this reaction through an Sk2 mechanism however, this reaction can also be represented through an S -l reaction involving initial... 

Table II shows that p-methoxybenzyl alcohol reacts about 104 times as fast as the parent benzyl alcohol. It is a well-established fact that a...

Primary, secondary, and tertiary alcohols react with 4-methoxybenzyl-2-pyri-dylthiocarbonate [197.1, Scheme 4.197] in the presence of siJver(l) triflate at room temperature within 2 h to give the corresponding p-methoxybenzyl ethers in 72-90% yield.3 4 No W-alkyiation is observed with amides, carbamates and pyrimidine-type nitrogens and no ester migrations, -eliminations, or epimerisa-tions besmirch the method. Reagent 197.1 is a yellow crystalline solid at 0 °C that can be stored for several months without noticeable decomposition. It is prepared in 80% yield by the reaction of p-methoxybenzyl alcohol with di-(2-pyridyl)thiocarbonate. 

PhenyT9-xanthenyl Phenylmercuric acetate 4-Methoxybenzyl (p-methoxybenzyl) p-Methoxybenzyl chloride p-Methoxybenzyloxymethyl p-Methoxybenzyl alcohol 2,2,5,7,8-Pentamethylchroman-6-sulfonyl Pentamethyldiethylenetriamine Pentamethylbenzenesulfonyl... 

The reaction of isoprene monoxide with a range of alcohol pronucleophiles in the presence of the ligand (3 mol%), Pd2dba3.CHCl3 (1 mol%) and triethylboron (1 mol%) gave the glycol monoethers in excellent yield and enantiomeric excess. The use of p-methoxybenzyl alcohol and 3-nonyl-3,4-epoxybut-1-ene afforded an intermediate that was converted into (—)-malyngolide (eq 8). ... 

Methoxybenzo[c]phenanthrene, 81 p-Methoxybenzyl alcohol, 669 p-Methoxybenzyl chloride, 668,1088 P Methoxybenqil oyanlda, 1088... 

Using this method, benzylic alcohols with electron-deficient and electron-neutral groups were oxidized in good to excellent yields. However, electron-rich benzylic alcohols such as p-methoxybenzyl alcohol failed to afford the target products due to side reactions. 

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