Benzylic alcohols secondary

Diphenylphosphoryl azide also gives good conversion of primary alkyl and secondary benzylic alcohols to azides in the presence of the strong organic base diazabicyc-loundecane (DBU). These reactions proceed by O-phosphorylation followed by Sw2 displacement.78... 

Photolabile linkers play an important role in solid-phase organic synthesis (SPOS) due to their stability under both acidic and basic conditions. The ONb photolabile linker was modified to improve cleavage rates and yields Fmoc-Tos-OFI was released in 87% yield after 23 h (Scheme 4) [24]. Specifically, the primary alcohol was changed to a secondary benzylic alcohol and the attachment to the resin was through an alkyl chain as opposed to an amide function. Linker 20 was used for the production of carboxylic acids or carbohydrates. A second example... 

Internal hydrogen bonding promotes imidazole transfer in the reaction of primary and secondary benzyl alcohols with CDI (A) or ImSOIm (B) [15],[16]... 

In some instances, treatment of polyfunctional benzylic alcohols with acid in the presence of organosilicon hydrides causes multiple functional group transformations to occur simultaneously. This phenomenon is illustrated by the reduction of the secondary benzylic alcohol function and concomitant loss of the methoxymethyl protecting group of 2-(l-hydroxydecyl)-5-methoxy-l-(methoxy-methyleneoxy)naphthalene upon treatment with Et3SiH/TFA in dichloromethane (Eq. 26).167... 

The secondary benzylic alcohol l-phenylethan-l,2-diol requires 20 hours of treatment at room temperature to produce a 64% yield of 2-phenylethanol (Eq. 43).137 Under the same conditions, methyl mandelate fails to undergo reduction, presumably because of the greater carbocation-destabilizing effect of a neighboring carboalkoxy compared to a hydroxymethyl group (Eq. 43).137... 

Decyl-5-methoxy-l-naphthol [Reduction of a Secondary Benzylic Alcohol to a Methylene Group with Concomitant Loss of a MOM Protecting Group].167... 

Chaudhuri et al. (216) reported that the dinuclear bis(phenoxyl)dicopper(II) species [Cu2(Ls )2]Cl2 (Fig- 30) reacts under anaerobic conditions in dry THF in a stoichiometric fashion with primary and secondary alcohols (ethanol, benzyl alcohol, 2-propanol, diphenylcarbinol, and 2-butanol) with formation of two different products, namely, aldehydes (or ketones) and 1,2-diols (and/or other oxidative C— C coupling products). 

The enyne-allene 12 having a methyl substituent at the allenic terminus was likewise prepared from the corresponding enediynyl propargylic alcohol 11 (Scheme 20.4). The presence of a methyl group accelerates the rate of cyclization by approximately sixfold and 12 cyclizes with a half-life of -3.6 min at 78 °C. The formation of a more stable secondary benzylic radical is apparently responsible for the rate enhancement. 

Specific dehydrogenation of secondary benzylic alcohols (Table 10.39)... 

Ketones are obtained in good yields from secondary benzylic alcohols (entry 3), whereas the oxidation is less satisfactory with aliphatic alcohols (entries 4 and 5). This is a... 

Scheme 23 Competitive oxidations between primary and secondary benzyl alcohols by using the bulky bismuthonium salts [90]...

Tertiary benzylic nitriles are useful synthetic intermediates, and have been used for the preparation of amidines, lactones, primary amines, pyridines, aldehydes, carboxylic acids, and esters. The general synthetic pathway to this class of compounds relies on the displacement of an activated benzylic alcohol or benzylic halide with a cyanide source followed by double alkylation under basic conditions. For instance, 2-(2-methoxyphenyl)-2-methylpropionitrile has been prepared by methylation of (2-methoxyphenyl)acetonitrile using sodium amide and iodomethane. In the course of the preparation of a drug candidate, the submitters discovered that the nucleophilic aromatic substitution of aryl fluorides with the anion of a secondary nitrile is an effective method for the preparation of these compounds. The reaction was studied using isobutyronitrile and 2-fluoroanisole. The submitters first showed that KHMDS was the superior base for the process when carried out in either THF or toluene (Table I). For example, they found that the preparation of 2-(2-methoxyphenyl)-2-methylpropionitrile could be accomplished h... 

They used this new oxidizing reagent for a rapid and selective oxidation of primary and secondary benzylic alcohols to the corresponding aldehydes and ketones in good to excellent yields. BTPCP was later used for oxidation of various alkylbenzenes under neutral conditions in aqueous CH3CN to the corresponding carbonyl compounds in good yields (equation 34) °. ... 

Very recently, Hu et al. claimed to have discovered a convenient procedure for the aerobic oxidation of primary and secondary alcohols utilizing a TEMPO based catalyst system free of any transition metal co-catalyst (21). These authors employed a mixture of TEMPO (1 mol%), sodium nitrite (4-8 mol%) and bromine (4 mol%) as an active catalyst system. The oxidation took place at temperatures between 80-100 °C and at air pressure of 4 bars. However, this process was only successful with activated alcohols. With benzyl alcohol, quantitative conversion to benzaldehyde was achieved after a 1-2 hour reaction. With non-activated aliphatic alcohols (such as 1-octanol) or cyclic alcohols (cyclohexanol), the air pressure needed to be raised to 9 bar and a 4-5 hour of reaction was necessary to reach complete conversion. Unfortunately, this new oxidation procedure also depends on the use of dichloromethane as a solvent. In addition, the elemental bromine used as a cocatalyst is rather difficult to handle on a technical scale because of its high vapor pressure, toxicity and severe corrosion problems. Other disadvantages of this system are the rather low substrate concentration in the solvent and the observed formation of bromination by-products. 

The benzyl zinc reagents 38 can be reacted with various electrophiles E-X including aldehydes (or ketones) and acid chlorides, thus providing access to secondary (or tertiary) alcohols and benzylic ketones, respectively. Examples are given in Table 321. 

Substrates suitable for oxidative conversion into carbonyl compounds are alkenes, primary or secondary alcohols, and benzyl halides. Polystyrene-bound alkenes have been converted into aldehydes (with the loss of one carbon atom) by ozonolysis followed by reductive cleavage of the intermediate ozonide (Entry 1, Table 12.3). 

In this example, the product can be variously described as a secondary alcohol, a benzyl ic alcohol, and an allylic alcohol. Can you identify the structural reason for each classification ... 

Interestingly, the simple p-quinone (84a) is also able to oxidize certain unsaturated alcohols under harsh conditions.98 Because of its lower oxidation potential, p-quinone only oxidizes unsaturated alcohols devoid of steric hindrance and able to generate very stabilized carbocations. Thus, it is able to react with primary cinnamyl alcohols but not with secondary cinnamyl alcohols, simple allylic alcohols and benzylic alcohols. 

Protodedeuteration reaction has, however, some limitations. It cannot be used to study compounds subject to secondary condensation in acidic medium, such as certain benzyl alcohol and benzyl ether derivatives. Moreover, the partial rate factors depend greatly on the medium used because different acids show different degrees of selectivity. For instance, the reported partial rate factors for the para position of toluene (/PMe) range from 170 (in sulfuric acid at 6S°C.) (13) to 4000 (in hydrogen bromide) 22). 

As noted above, this correlation and that of Fig. 1 are deficient in not recognizing that the product of the nucleophilic reaction is not the alcohol, as implied by the correlation with pATR, but the protonated alcohol. However, it is reasonable to suppose that variation of the pATas for O-protonation of the alcohols, which are required to correct values of ATR, are small compared with variations in pifR itself (and thus pATH2o) and would not significantly affect the quality of the correlation. It is also true that the correlation is dominated by the large and variable values of pA n.o for aromatic products of deprotonation. These tend to obscure variations in product ratios for tertiary alkyl and secondary benzylic cations which are the focus of a previous discussion of this partitioning by Richard.5... 

Triflic acid is also efficient in the alkylation of electron-rich aromatics (anisole, 1,3-dimethoxybenzene, 2-methylfurane, pyrrole, benzofurane, indole) with secondary benzylic alcohols and 3-phenylallyl alcohols (50°C, 1-9 h, 66-95% yield).201 Benzene, toluene, and halobenzenes are also alkylated with hydroxy-biindantetraone 53 in triflic acid within 1-2h202 [Eq. (5.78)]. Suprisingly, however, the primary products (with the exception of the 4-methylphenyl-substituted compound) undergo rearrangement upon prolonged treatment to yield alkenes... 

Another advantage of this approach is that we can now use electrophilic substitution on the pyrrole to add the rest of the molecule. So the secondary benzylic alcohol 106 might well cyclise to 105 with Lewis acid catalysis as the cation will be reasonably stable and the reaction is intramolecular. But the Friedel-Crafts alkylation to give 107 will not succeed as the cation would be primary. 

The influence of the alcohol on the reaction was evaluated (Scheme 26). The results of a competition experiment between the alcohols are shown in Table 7. Both alcohols were treated with mono-alkoxysilane le using 10 % Pd/C as the catalyst. The silyl ketals of both alcohols were isolated as a mixture and the area under the methine protons, from the (+)-ethyl lactate moiety of both silyl ketals, was compared by NMR analysis. The difference in reactivity of primary, versus secondary, versus tertiary alcohol was small. The differences in reactivity range from 1.5 1 for 1° vs 2°, to 3 1 for 1° vs 3°. The reactivity of a benzyl alcohol is slower than the aliphatic alcohol as shown in entries 4 to 6. Entries 4 and 5 show an increase in the ratio of 1° 2° alcohol and a decrease in ratio for the 2° 3° for the secondary benzyl alcohol. Entries 6 and 7 confirm that benzyl alcohols are less reactive than aliphatic alcohols. The inductive electron withdrawing effect of the aryl group in the benzyl alcohol renders it less nucleophillic and this may affect the rate of reaction with the silane. Although the difference in reactivity is small, this trend may be informative. The influence of the alcohol s nucleophilicity on the reaction mechanism will be addressed in a later section. 

Answer A is a secondary benzyl chloride. It, thus, can be prepared by treating the alcohol C with HC1. 

These complexes were screened in the oxidation of sec-phene ihyl alcohol with acetone as the solvent and K2CO3 as a base [59]. It was found that the presence of smaller substituents on the nitrogen atoms of the NHC ligand promote catalytic activity, and the dicationic complex, 25a, is the most active catalyst. Accordingly, use of complex 25a enabled the catalyst loading to be lowered to 0.025 mol%, and 3200 turnovers were achieved. The utility of this catalyst was demonstrated for both primary and secondary benzylic alcohols and several aliphatic alcohols. 

This C - H activation event is reversible, and is required to achieve catalytic turnover [62], A series of alcohols, mostly secondary benzylic examples, have been oxidized using this catalyst. The catalytic activity does not match that of the Ir examples described above, but it has been used in several tandem reactions that feature both dehydrogenation and hydrogenation steps to achieve interesting transformations. One example is a tandem alcohol oxidation/Wittig reaction/alkene hydrogenation sequence (Scheme 9) [61,62],... 

---