Hydroxymethyl compounds

In some instances the solvents may react with the substrate during the irradiation. For example, 3,6-dichIoropyridazine, when irradiated in acidified methanol, gives a mixture of raonoraethylated (56), dimethylated (57) and hydroxyraethylated (58) compounds. Further transformation of the hydroxymethyl compound (58) results in the formation of y-Iactones (59) and succinates (60 Scheme 20). 

Trideuteriomethyl Grignard-reagent has also been used for the preparation of the d3-labeled epimeric D-homo hydroxymethyl compounds (255) and (256). The isotopic purity of these products is greater than 98%. ... 

Dilute hydrochloric acid reacts with the methoxymethyl derivative 6 to give the hydroxymethyl compound 7. The hydroxymethyl group of the latter can be removed by treatment with ammonia solution to give ethyl 5-oxo-4,5-dihydro-177-1,4-diazepine-l -carboxylatc (8).31... 

Hydroxyl number, 94 Hydroxymethylated compounds, 403 Hydroxymethylated phenol, 378. See also Hy droxy me thy lphenol Hydroxymethyl condensation reactions, 399-400... 

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). 

Two other polycyclic hydrocarbons, 3-methylcholanthrene and 7,12-dimethylbenzanthracene are oxidized during arachidonate metabolism (21,26). Hydroxymethyl compounds that do not arise from arene oxides appear to be the products formed from 7,12-dimethylbenzanthracene. ... 

In this reaction the Y-hydroxymethyl compound first formed is reduced by excess of formaldehyde ... 

Several reaction mechanisms are possible for the cleavage of A-(hydroxy-methyl) intermediates [214], In the case of derivatives of amides and imines, the reaction is base-catalyzed, with the rate-limiting step being deprotonation of the A-(hydroxymethyl) compound (which has a pKa of ca. 13 Fig. 

These and other interesting results allow quantitative insight into the rate of breakdown of N-(hydroxymethyl) compounds (i.e., carbinolamines (hemi-aminals)), the reaction mechanisms of which we examined in Sect. 8.7.3 (see, in particular, Fig. 8.20) [80 - 82], These carbinolamines, we recall, are major metabolic intermediates in oxidative N-dealkylation reactions resulting from cytochrome P450 catalyzed hydroxylation of the C-atom adjacent to the... 

Cyclopropanation is an important synthetic method, and enantioselective catalytic reactions of olefins and diazoacetates provide access to valuable products with biological activity. In general, these reactions are conducted in anhydrous solvents and in several cases water was found to diminish the rate or selectivity (or both) of a given process. Therefore it came as a surprise, that the Cyclopropanation of styrene with (+)- or (-)-menthyl diazoacetates, catalyzed by a water-soluble Ru-complex with a chiral bis(hydroxymethyldihydrooxazolyl)pyridine (hm-pybox) ligand proceeded not only faster but with much Wgher enantioselectivity (up to 97 % e.e.) than the analogous reactions in neat THF or toluene(8-28 % e.e.) (Scheme 6.34) [72]. The fine yields and enantioselectivities may be the results of an accidental favourable match of the steric and electronic properties of hm-pybox and those of the menthyl-dizaoacetates, since the hydroxyethyl or isopropyl derivatives of the ligand proved to be inferior to the hydroxymethyl compound. Nevertheless, this is the first catalytic aqueous cyclopropanation which may open the way to other similar reactions in aqueous media. 

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. 

Condensation of urea with formaldehyde leads to products of various structures and properties according to the experimental conditions (pH, temperature, reaction time, molar ratio of components). The condensation is generally carried out in basic medium, resulting essentially in the formation of hydroxymethyl compounds some oxymethylene groups are also formed, particularly on heating. Mono-, di-, and trihydroxymethylurea have been proved to be primary... 

The soluble hydroxymethyl compounds can be chemically modified, before crosslinking, by reaction with monofunctional compounds (e.g., by esterification or ether formation). The properties of the starting materials as well as the crosslinked end products can thereby be substantially altered. For example, by partial etherification with butanol the hydroxymethyl compounds, originally soluble only in polar solvents, become soluble also in nonpolar solvents (toluene), without losing their ability to undergo self-crosslinking. 

Urea-formaldehyde resins are generally prepared by condensation in aqueous basic medium. Depending on the intended application, a 50-100% excess of formaldehyde is used. All bases are suitable as catalysts provided they are partially soluble in water. The most commonly used catalysts are the alkali hydroxides. The pH value of the alkaline solution should not exceed 8-9, on account of the possible Cannizzaro reaction of formaldehyde. Since the alkalinity of the solution drops in the course of the reaction, it is necessary either to use a buffer solution or to keep the pH constant by repeated additions of aqueous alkali hydroxide. Under these conditions the reaction time is about 10-20 min at 50-60 C. The course of the condensation can be monitored by titration of the unused formaldehyde with sodium hydrogen sulfite or hydroxylamine hydrochloride. These determinations must, however, be carried out quickly and at as low temperature as possible (10-15 °C), otherwise elimination of formaldehyde from the hydroxymethyl compounds already formed can falsify the analysis. The isolation of the soluble condensation products is not possible without special precautions, on account of the facile back-reaction it can be done by pumping off the water in vacuum below 60 °C imder weakly alkaline conditions, or better by careful freeze-drying. However, the further condensation to crosslinked products is nearly always performed with the original aqueous solution. 

Melamine dissolves in aqueous formaldehyde solution on warming, with the formation of W-hydroxymethyl compounds.The latter are crystalline substances that dissolve in hot water but are only slightly soluble in cold water. If a sample of the reaction mixture is cooled immediately after the melamine has been completely taken into solution,the poorly soluble W-hydroxymethyl compounds precipitate. 

Metabolism studies showed that the major metabolites of the components of ivermectin in cattle, sheep, and rats were 24-hydroxymethyl compounds, whereas major metabolites in swine were 3-0-desmethyl compounds. Identification of the 24-hydroxymethyl metabolites has not been yet achieved in swine, whereas identification of Hie 3-O-desmetlryl metabolites has not been made possible in cattle or sheep (54, 55). Recent metabolism studies (56) in cattle, swine, and rats have indicated, however, diat the metabolism of avermectins was qualitatively similar for all three species. There were quantitative differences both between species and between compounds for a given species, but all three species produced... 

It was shown (Woodcock [25]) that intermediate hydroxymethyl compounds may be formed as for example those of type (V)... 

Pyridinediylbisphosphonium salts react with methanol in the presence of ammonium peroxodisulphate to give the 5-hydroxymethylated compound when radical conditions were absent, nucleophiles gave the 4-substituted products selectively746. 

The hydroxymethyl compound 43 with acyl halides gave esters of the type 48.166 The acid 49 has reacted via the acyl chloride to give a number of amides of the type 50.154,156 Thionyl chloride converts 43... 

Ames and co-workers have reported the synthesis of some aminoethyl indolizines.141 Workers at Keele University have investigated the preparation of hydroxymethyl and aminomethyl derivatives.142 They obtained the 2-, 3-, and 6-hydroxymethyl compounds by lithium aluminum hydride (LAH) reduction of the esters. However, compound 93 gave inseparable mixtures on reduction, and whereas the 2-amino-methyl compound could be made by reduction of the corresponding... 

Formation of hydroxymethyl compounds under acidic or basic conditions at low temperature, 50-100°C (Eq. 2.48). A complicated reaction mixture can result. 

Condensation of these hydroxymethyl compounds to form methylene or dimethylene ether bridges, leading to oligomers (Eqs (2.49) and (2.50)). At T < 100°C, the reactions are relatively slow. 

Formaldehyde, along with other short-chain aldehydes such as acetaldehyde, is a low molecular weight, volatile, reactive contaminant that can be present at low levels from a variety of sources (e.g., excipients such as polyethylene oxide, polyethylene glycol (64,65), or from carbohydrate degradation (66), solvent contamination (51), packaging materials (52), etc.). Formaldehyde is known to react with amines (Fig. 33) to form a reactive N-hydroxymethyl compound (a hemiaminal) that can further react with other nucleophiles. Reaction of formaldehyde with amino acids (67) can cause... 

In addition to the preparation of a- and /3-hydrastine described above from the betaine (64), another conversion of a tetrahydroberberine into hydrastine has been reported. Acetylophiocarpine, on treatment with ethyl chloroformate, gives the acetoxy-derivative of (88), which can be hydrolysed to the hydroxymethyl compound and then oxidized to the aldehyde by pyridinium perchlorate. Hydrolysis of the acetoxyl group afforded the hemi-acetal (93 R = H), conversion of which into the mixed acetal (93 R = Et) protected the aldehyde system during reduction of N—C02Et to NMe by lithium aluminium hydride. Hydrolysis of the acetal, followed by oxidation, then gave a-hydrastine, and a similar sequence of reactions starting from O-acetyl-13-epi-ophiocarpine afforded / -hydrastine.119 Methods of synthesis of alkaloids of this group have been reviewed.120... 

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]. 

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