Phenol benzyl alcohol, reactivity with

Relatively little basic information has been published regarding the kinetics of phenol-formaldehyde intermediates, especially of phenols, methylol phenols, benzyl alcohol and benzylic ethers with isocyanates. Due to the fact that a typical resole contains both phenolic and benzylic hydroxyl groups, it was of interest to determine their reactivity toward isocyanates in the presence of various catalysts, as well as the effect of substitution on their reactivity. This investigation describes the kinetics of model phenols and model benzyl alcohols with phenyl isocyanate catalyzed with either a tertiary amine (dimethylcyclo-hexylamine, DMCHA) or an organotin catalyst, dibutyltin dilaurate (DBTDL) in either dioxane or dimethylformamide solution. 

EFFECT OF CATALYSTS ON THE REACTIVITY OF PHENOL BENZYL ALCOHOL AND ETHYL ALCOHOL WITH PHENYL ISOCYANATE... 

Substitution Reactions on Side Chains. Because the benzyl carbon is the most reactive site on the propanoid side chain, many substitution reactions occur at this position. Typically, substitution reactions occur by attack of a nucleophilic reagent on a benzyl carbon present in the form of a carbonium ion or a methine group in a quinonemethide stmeture. In a reversal of the ether cleavage reactions described, benzyl alcohols and ethers may be transformed to alkyl or aryl ethers by acid-catalyzed etherifications or transetherifications with alcohol or phenol. The conversion of a benzyl alcohol or ether to a sulfonic acid group is among the most important side chain modification reactions because it is essential to the solubilization of lignin in the sulfite pulping process (17). 

Consistent with the results of this study is the outcome of the oxidation of 4-X-substituted phenols by use of PINO, generated from HPI with Pb(OAc)4 at 25 °C in MeCN containing 1% AcOH . The reactivity (fcn) of PINO towards phenolic O—H bonds (BDE 85-90 kcal moC ) was about one order of magnitude higher than that measured towards the C—H bond of benzyl alcohols (cf. Table 4). A p value of —3.1 was obtained from plotting log kn vs. for this reaction, where removal of H-atom from the phenolic O—H bond (which is weaker than the O—H bond of aliphatic or benzyl alcohols) induces an oxidative phenolic coupling with the PINO moiety. In view of the low redox potential of the substituted phenols (in the 0.8-1.1 V/NHE range), and of the substantial value of the kinetic isotope effect = 3.1-3.7 measured, ... 

Although phosphorylation of AChE by OPs is heavily influenced by the electron-withdrawing power of the leaving group, carbamylation by methyl carbamates is also greatly dependent on molecular complementarity with the conformation of the enzyme as well as reactivity of the molecule. In general, phenolic and oxime moieties are more reactive than benzyl alcohol groups. 

Brunow, G., Sipila, J., and Makela, T. (1989) On the mechanism of formation of non-cyclic benzyl ethers during lignin biosynthesis. Part 1 The reactivity of (3-0 quinone methides with phenols and alcohols. Holzforschung 43(1), 55-59. 

The reactivity of the model phenols and benzyl alcohols with phenyl isocyanate was determined in the presence of a tertiary amine (DMCHA) and a tin catalyst (DBTDL) by measurement of the reaction kinetics. The experimental results based on initial equal concentrations of phenyl isocyanate and protic reactants showed that the catalyzed reactions followed second order reaction with respect to the disappearance of isocyanate groups (see Figure 1). It was also found that a linear relationship exists between the experimental rate constant kexp, and the initial concentration of the amine catalyst (see Figure 2). In the case of the tin catalyst, the reaction with respect to catalyst concentration was found to be one-half order (see Figures 3-4). A similar relationship for the tin catalyzed urethane reaction was found by Borkent... 

The effect of type of catalyst on the reactivity of phenol and benzyl alcohol with phenyl isocyanate can be seen in Table III. In the case of tertiary amine (DMCHA), there is a relatively small difference in the reactivity of both the phenol and benzyl alcohol with phenyl isocyanate. Using DBTDL as catalyst, benzyl alcohol was found to be 26 times more reactive than phenol in the reaction with phenyl isocyanate. 

Model studies based on substituted phenols and benzyl alcohols showed that the presence of substituents in the ortho position in benzyl alcohol had a relatively small effect on the reactivity of the hydroxyl group with isocyanate in the presence of tertiary amine catalyst (DMCHA). In contrast, similar substitution in phenols significantly affected the reactivity of the... 

Pd-catalyzed reaction of a-n hthol, isobutyraldehyde, and CO in the presence of CF3CO2H afforded naphthofuran-2(3/7)-one 28 in 79 % yield. The reaction is explained hy acid-catalyzed formation of l-(2-naphthyl)butanol 27, followed by carbonylation of the benzylic alcohol. Although its reactivity is lower, the phenol derivative 29 reacted with acetaldehyde to generate the benzylic alcohol 30, which was carbonylated to provide the benzofiiranone 31 in 54% yield [14]. 

In 2014, Canesi s group also reported on a remarkable application of their chemistry that enabled them to develop an asymmetric synthesis of the tetracyclic main core of kaurane diterpenes [131]. The phenolic non-conjugated enyne 249 was elaborated to fulfill the reactivity and stereochemistry requirements of the intended oxidative cationic polycyclization [132], in tandem with apinacolic transposition. After chlorination of the benzylic alcohol of 249 with inversion of configuration, the use of BTI rapidly promoted this dearomative tandem process, which thus... 

As seen in the retro-synthetic Scheme 5.3, intermediate 15 is useful for both routes. The choice of benzyl protection group was made based on the robust stability of benzyl phenol ethers toward most reactions and several possible avenues to remove it, although it was reported from Medicinal Chemistry that benzyl group removal via hydrogenolysis posed challenges in this compound. The choice of iodide substitution was born out of the known high reactivity of iodides in the Ullmann-type coupling reaction with alcohols and the robust stability of aryl iodides in many other common reactions. 

Syntheses of alkyl phenyl ethers, C,H, OR, are carried out by refluxing aqueous or alcoholic solutions of alkali phenolates with alkyl halides the yields vary with the nature of the alkyl halides (40-80%). The reactive halogen in benzyl halides is easily replaced by an alkoxyl group (95%). ° The choice of a solvent is sometimes important. Thus, in the preparation of the alkyl ethers of o- and p-hydroxybiphenyl from a mixttire of the phenol, alkyl halide, and powdered potassium hydroxide, high yields are obtained using acetone as a solvent, whereas, with alcohol as solvent, only small yields are obtained. Triarylmethyl chlorides react with alcohols directly (97%). ... 

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