N-Hydroxymethyl groups

A one-pot conversion of benzyl alcohols to benzyl fluorides by treatment of the alcohols with a combination of methanesulfonyl fluoride, cesium fluoride and 18-crown 6 ether in tetrahydrofuran has been repotted The reaction involves mesylation of the alcohols followed by cleavage of the resultant mesyl esters with a fluoride ion The reaction has been extended also to certain heterocycles bearing the N hydroxymethyl group [43] (equation 31)... 

Crosslinking then occurs between the N-hydroxymethyl group and a free amino group from an adjacent polypeptide ... 

N,]S7-bis(methoxymethyl)uron was first isolated and described in 1936 (41), but was commercialized only in 1960. It is manufactured (42) by the reaction of 4 mol of formaldehyde with 1 mol of urea at 60°C under highly alkaline conditions to form tetramethylolurea [2787-01-1]. After concentration under reduced pressure to remove water, excess methanol is charged and the reaction continued under acidic conditions at ambient temperatures to close the ring and methylate the hydroxymethyl groups. After filtration to remove the precipitated salts, the methanolic solution is concentrated to recover excess methanol. The product (75—85% pure) is then mixed with a methylated melamine—formaldehyde resin to reduce fabric strength losses in the presence of chlorine, and diluted with water to 50—75% soHds. Uron resins do not find significant use today due to the greater amounts of formaldehyde released from fabric treated with these resins. 

The 8-methyl-8,14-cycloberbine 364, derived from the protoberberine 324 via the betaine 363, was reduced with sodium borohydride or lithium aluminum tri-tert-butoxyhydride to give a diastereoisomeric mixture of cis-and trans-alcohols (7.8 1 or 1 7.8, respectively) (Scheme 64).t)n exposure to formaldehyde the mixture underwent N-hydroxymethylation and subsequent intramolecular substitution on the aziridine ring to give the oxazolidine 365. Removal of the hydroxyl group in 365 was accomplished by chlorination followed by hydrogenolysis with tributyltin hydride. Reductive opening of the oxazolidine 366 with sodium cyanoborohydride afforded ( )-raddeanamine (360), which has already been converted to ochotensimine (282) by dehydration. 

The synthesis of L-ribofuranose derivatives from 16a has been carried out by Walker and Hogenkamp (35). The procedure involves oxidation of the hydroxymethyl group of 16a with dimethyl sulfoxide N,N dicyclohexylcarbodiimide and acid hydrolysis of the protecting group to give L-riburonic acid, which was converted into methyl (methyl a,/ -ribofurano-sid)uronates (26). Reduction of 26 with sodium bis(2-methoxyethoxy)alu-minum hydride gave the chromatographically separable anomers of methyl L-ribofuranoside (27). 

Tolfenamic acid is used as an injectable formulation in cattle and swine. In rats and target animals, tolfenamic acid is metabolized by hydroxylation either of the methyl or the methylchlorophenyl group producing two metabolites further oxidation of the hydroxymethyl group to the corresponding aldehyde or carboxylic acid can produce two additional metabolites. The two hydroxylated metabolites of tolfenamic acid, N-(2-hydroxymethyl-3-chlorophenyl)-anthranilic acid and N-(2-hydroxymethyl-3-chloro-4-hydroxyphenyl)-anthranilic acid, are much less potent than the parent compound in terms of anti-inflammatory and analgesic... 

The composition of solutions of the 2-heptuloses has been determined, and discussed, by Angyal and Tran.92 These ketoses are different from other reducing sugars inasmuch as there are two hydroxymethyl side chains attached to the pyranose ring. In the a-pyranose form, they are cis to each other and will therefore both be equatorial in the preponderant chair form. In the / -pyranose, however, one or other of the hydroxymethyl groups has to be axial and, in consequence, the / anomers are disfavored in only one solution (that of the altro isomer) was the yS-pyra-nose detected in the 13C-n.m.r. spectrum.92... 

NMR studies of 4,6-bis- and 2,4,6-tris-(MA-dialkylamino)-l, 3,5-triazines show correlated rotations of the alkyl groups in the dialkylamino substituents. Unsymmetrical 2-chloro-, 2-alkoxy- and 2-aryloxy-4,6-bis-(di-/i-alkylamino)-l,3,5-triazines show two non-equivalent n-alkyl groups due to restricted rotation [95JCS(P2)785]. Calculations of the favoured conformations of 2-[A-(hydroxymethyl)-ALmethyl]-4,6-bis-dimethylamino-l,3,5-triazine using MNDO and PM3 methods have also been made [95JCS(P2)469]. 

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