Hydroxymethyl compounds methyl groups

Under acidic conditions, furfuryl alcohol polymerizes to black polymers, which eventually become crosslinked and insoluble in the reaction medium. The reaction can be very violent and extreme care must be taken when furfuryl alcohol is mixed with any strong Lewis acid or Brn nstad acid. Copolymer resins are formed with phenoHc compounds, formaldehyde and/or other aldehydes. In dilute aqueous acid, the predominant reaction is a ring opening hydrolysis to form levulinic acid [123-76-2] (52). In acidic alcohoHc media, levulinic esters are formed. The mechanism for this unusual reaction in which the hydroxymethyl group of furfuryl alcohol is converted to the terminal methyl group of levulinic acid has recendy been elucidated (53). 

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

When the 5 and 6 positions of camphor are blocked by substituents, hydroxylation at other positions may take place. For example, the quaternary methyl group of 5,5-difluorocamphor is hydroxylated to the 9-hydroxymethyl compound (Figure 3.18a) (Eble and Dawson 1984). 

Of the direct methyl group replacements reported, small groups such as hydroxymethyl and fluoromethyl are tolerated, while larger groups in this position result in compounds with reduced in vivo potency and efficacy. The n-butyl derivative (159) was the only C9 methyl replacement analogue that showed a marked effect on hypothermia (5°C decrease at 168/rmol/kg ED50 not calculated) [116]. 

Section III,B> ) The two methyl groups in 34 were formed from the corresponding methyl esters via reduction to the bis-hydroxymethyl compound followed by ditosylation and reduction with LAH. Both the intermediate diester and the derived dialcohol were separately cyclized to give the corresponding octahydrodibenzothiophenes (50% and 80%, respectively). However, no attempt to dehydrogenate these compounds to the dibenzothiophenes was made. This reaction obviously has considerable potential. 

Fig. 2. Preparation of CSG affinity resins of compound without effective inherent functional groups after bioconversion using S9 mixture, (a) Preparation of CSG affinity resins of valdecoxib (5) that has no effective inherent functional groups for immobilization, (b) Capture of C0X2 from sheep placenta lysate (Fig. 2b upper). Due to previously reported structure-activity relationships (8), we believe that conversion of the methyl group to hydroxymethyl was achieved by the S9 treatment. Moreover carbonic anhy-drase type 2 (CA2) was also captured by these resins from THP1, a human leukemic cell line, lysates (Fig. 2b lower). CA2 has been recently reported to be specifically inhibited by valdecoxib at 43 nM (10).

Overend and co-workers reported numerous syntheses of sugars having methyl, hydroxymethyl, and formyl groups attached to carbon atoms of the sugar by the use of Grignard reagents,429 organolithium compounds,470 and diazomethane.471... 

The cationic groups can also be introduced by other methods such as chloro-methylation and quatemization [13] or be converted by curing suitable hydroxymethyl compounds [14] with a pigment. In this way, for example, the lightfast cationic blue paper dye 28 can be obtained with C.I. Pigment Violet 23 51319 [6358-30-1]. 

A route to /3-methyl-tetrahydroberberines has been developed from the hydra-stinine derivative (72), which can be acylated with the dimethoxyhomophthalic anhydride (73) to give acid (74). Reduction of this with lithium aluminium hydride followed by further reduction of the toluene-p-sulphonyl ester of the resulting hydroxymethyl compound yields the 13-methyl compound.91 An essentially similar synthesis of oxoberberines bearing a carboxy-group at C-13, of general type (74), has been reported by other workers.92... 

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