Phenols hydroxyalkylation

Concerning the structure of substituent R, numerous functional group-containing substituents have been investigated, functional groups being, that is, olefinic-, acetylenic-, phenolic-, hydroxyalkyl-, mercaptoalkyl-, carboxyalkyl-, amino-, amino-alkyl-, haloalkyl-, and other groups. Some of these monomers act as a reactive or functional monomer. 

Chiral glyoxylates have been used to effect of/z o-hydroxyalkylation of phenols via coordinative complexes. In this way, optically active 2-hydroxymandehc esters have been obtained with up to 94% diastereoselectivity (36). 

Other modifications of the polyamines include limited addition of alkylene oxide to yield the corresponding hydroxyalkyl derivatives (225) and cyanoethylation of DETA or TETA, usuaHy by reaction with acrylonitrile [107-13-1/, to give derivatives providing longer pot Hfe and better wetting of glass (226). Also included are ketimines, made by the reaction of EDA with acetone for example. These derivatives can also be hydrogenated, as in the case of the equimolar adducts of DETA and methyl isobutyl ketone [108-10-1] or methyl isoamyl ketone [110-12-3] (221 or used as is to provide moisture cure performance. Mannich bases prepared from a phenol, formaldehyde and a polyamine are also used, such as the hardener prepared from cresol, DETA, and formaldehyde (228). Other modifications of polyamines for use as epoxy hardeners include reaction with aldehydes (229), epoxidized fatty nitriles (230), aromatic monoisocyanates (231), or propylene sulfide [1072-43-1] (232). 

A wide vanety of nucleophiles, such as 1-alkylpyrroles, furans, thiophenls [51], phenols [52], anilmes [55, 54], indoles [55], CH-acidic compounds [56, 57], as well as organolithium [56], Gngnard [57, 59], organocadmiura, and organozmc compounds [56], undergo C-hydroxyalkylation with trifluoropynivates to yield derivatives of a-trifluoromethyi a-hydroxy acids. 

Novolacs are prepared with an excess of phenol over formaldehyde under acidic conditions (Fig. 7.6). A methylene glycol is protonated by an acid from the reaction medium, which then releases water to form a hydroxymethylene cation (step 1 in Fig. 7.6). This ion hydroxyalkylates a phenol via electrophilic aromatic substitution. The rate-determining step of the sequence occurs in step 2 where a pair of electrons from the phenol ring attacks the electrophile forming a car-bocation intermediate. The methylol group of the hydroxymethylated phenol is unstable in the presence of acid and loses water readily to form a benzylic carbo-nium ion (step 3). This ion then reacts with another phenol to form a methylene bridge in another electrophilic aromatic substitution. This major process repeats until the formaldehyde is exhausted. 

Selective acetylations of hydroxyalkyl phenols by 1-acetylpyridinotriazolide were carried out with excellent results in 1 N aqueous sodium hydroxide solution 1283... 

We have found several examples in which adjacent cationic charge centers are shown to activate carboxonium electrophiles. A convenient method for studying this activation is through the use of the hydroxyalkylation reaction, a commercially important, acid-catalyzed condensation of aldehydes and ketones with arenes.10 It is used for example in the synthesis of bis-phenol A from acetone and phenol (eq 6). While protonated acetone is able to react with activated arenes like phenol, it is not capable of reacting with less nucleophilic... 

These reactions are real tautomerization reactions, but the quite common water elimination reactions can also completely change the redox property of a radical. A case in point is the radical derived from ethylene glycol which is a reducing a-hydroxyalkyl radical which is transformed by water elimination into the fomylmethyl radical (see below) whose oxidizing property has been discussed above [reaction (20)]. Similarly, the phenol OH-adduct is a reason-... 

Similarly, hydroxyalkylation with aldehydes or ketones is best accomplished with activated aromatic compounds, such as phenols.7 However, reaction even with chlorobenzene has been carried out with either para-banic acid or isatin using triflic acid (eqs 6-7).8,9... 

These important hydroxyalkyl- and hydroxyarylpyrazines should be considered as regular alcohols or phenols simply because their methods of preparation and their reactions are only minimally affected by the attached pyrazine ring. 

The following illustrative examples have been chosen from many different reaction types. For some specific reactions that are of interest mainly to the fragrance industry, e.g. epoxide rearrangement, reference is made to another chapter in this volume. Moreover, functionalization of aromatic compounds, comprising alkylations, acylations and hydroxyalkylations, and oxidations of phenol or olefins are not dicussed in this chapter, since these topics are covered by other authors. 

The Pechmann synthesis of coumarins via condensation of phenols with / -keto esters also involves an intramolecular hydroxyalkylation, following initial... 

However, Mannich bases arc more frequently employed as modifiers of polymeric products, as they arc involved in the. synthesis of derivatives having structures of type 392 or 393 (Fig. 153), as is evidenced by the epoxy oligomers 399, obtained from phenolic alkanolamines and ethylene oxide,in which the polycthcr chain involves both the phenolic and hydroxyalkyl moieties. 

Amino-alcohols and amino-phenols, having a second nucleophilic center (a hydroxy group), react with dichloride 102 preferentially on the amino group, and 2-(hydroxyalkyl)- or 2-(hydroxyaryl)benzisoselenazol-3(277)-ones 106 are produced (Scheme 39). Similarly, amino thiols give 2-thioalkyl- or 2-thioarylbenzisoselenazol-3(2//)ones 107 since the thiol groups are neither selenenylated nor acylated <2002T7531>. 

The hydroxyalkylation of phenolates with N-protected a-amino aldehydes gives /l-amino-orr/io-hydroxybenzyl alcohols with good to excellent diastereoselection. For... 

The hydroxyalkylation of phenols with chiral glyoxylates, followed by hydrolysis, gives regioselectively 2-hydroxymandelic acids with high enantioselectivity (eqnation 28). The crystal-structure determination of the titanium phenoxide complex shows evidence for chelation-controlled reaction giving the observed high enantioselectivities . ... 

Metal phenoxides are structurally related to metal enolates, and undergo aldol reaction to give C-hydroxyalkylated phenols. Reaction of formaldehyde and phenol to give phenol resins is of industrial importance, and occurs under either basic or... 

Hydroxyalkyl) TPs and phenols react to yield phenol ethers (e.g., 186, Scheme... 

The reactions of peracetic acid with p-alkyl and p-hydroxyalkyl phenols can be attribnted to electrophilic reaction of nnionized peracetic acid. Phenol was nnreactive bnt degradation occnrred when methoxyl or other electron donating snbstituents were added. Creosol, gnaiacol, vanillyl alcohol, or apocynol (V) are more readily oxidized at pH near 9, confirming that ionized phenols are more snsceptible than nnionized phenols to electrophilic attack. An observed decline in the rate of reaction above pH 9 can be attribnted to the decreased concentration of peracetic acid dne to ionization to peracetate ions. 

In contrast to many furan syntheses, this method uses 2-(2-hydroxyalkyl)phenoIs containing a leaving group at the benzylic carbon atom. Thus, 2-(I-isopropyl-thio-2-hydroxy)phenol cyclizes on heating with concentrated hydrochloric acid, but when 2-(2-hydroxyethyl)phenol was similarly treated, cyclization did not occur. When R = H, 2-unsubstituted benzofurans are obtained in good yield minor modifications were made in the synthesis of the 2-phenyl derivatives, and... 

Another route to coumarins is the Pechmann condensation of phenols with (3-ketoesters. The reaction proceeds via transesterification and intramolecular hydroxyalkylation, followed by dehydration, and is conventionally conducted using sulfuric acid as catalyst. Resorcinol and ethyl acetoacetate reacted sol vent-free over H-beta at 150 °C to give 7-hydroxy-4-methylcoumarin (78 % isolated yield) [85J. This is another perfumery ingredient which is also an intermediate for the insecticide I Iymecromone. 

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