Primary alcohols compounds with formaldehyde

The Mannich reaction consists in the condensation of formaldehyde with ammonia or a primary or a secondary amine and a compound containing at least one hydrogen atom of pronounced reactivity the active hydrogen atom may be derived from a methylene group activated by a neighbouring keto group, or from a nitroparaffin, or it may be the o- or p-hydrogen atoms in phenols. Thus when acetophenone is boiled in alcoholic solution with formaldehyde and dimethylamine hydrochloride, the Mannich base P-dimethylamino-propiopbenone hydrochloride (I) is readily formed ... 

Reaction of organometallic compounds with carbonyl compounds a. primary alcohols from methanal (formaldehyde)... 

The reaction of organometallic compounds with formaldehyde results in primary alcohols. In the electrostatic potential maps of the example below, the electron-rich (orange-red) carbon of the butylmagnesium bromide is seen to attack the electron-poor (blue) carbon of formaldehyde to give 1-pentanol. 

Hydroxypyrroles. Pyrroles with nitrogen-substituted side chains containing hydroxyl groups are best prepared by the Paal-Knorr cyclization. Pyrroles with hydroxyl groups on carbon side chains can be made by reduction of the appropriate carbonyl compound with hydrides, by Grignard synthesis, or by iasertion of ethylene oxide or formaldehyde. For example, pyrrole plus formaldehyde gives 2-hydroxymethylpyrrole [27472-36-2] (24). The hydroxymethylpyrroles do not act as normal primary alcohols because of resonance stabilization of carbonium ions formed by loss of water. 

The type of alcohol produced depends on the carbonyl compound. Substituents present on the car bonyl group of an aldehyde or ketone stay there—they become substituents on the carbon that bears the hydroxyl group in the product. Thus as shown in Table 14.3 (following page), formaldehyde reacts with Grignard reagents to yield primary alcohols, aldehydes yield secondary alcohols, and ketones yield tertiary alcohols. 

As examples of their addition to carbonyl compounds, Grignard reagents react with formaldehyde, H2C = 0, to give primary alcohols, with aldehydes to give secondary alcohols, and with ketones to give tertiary alcohols. 

Finally, reaction of primary, secondary, or tertiary alcohols 11 with Me3SiCl 14 in the presence of equivalent amounts of DMSO leads via 789 and 790 to the chloro compounds 791 [13]. n-Pentanol, benzyl alcohol, yS-phenylefhanol or tert-butanol are readily converted, after 10 min reaction time, into their chloro compounds, in 89-95% yield, yet cyclohexanol affords after reflux for 4 h cyclohexyl chloride 784 in only 6% yield [13] (Scheme 6.5). 1,4-Butanediol is cyclized to tetrahydrofuran (THF) [13a], whereas other primary alcohols are converted in 90-95% yield into formaldehyde acetals on heating with TCS 14 and DMSO in benzene [13b] (cf also the preparation of formaldehyde di(n-butyl)acetal 1280 in Section 8.2.1). 

Analysis of the Murchison meteorite led to a completely different type of phosphorus compound the only phosphorus-containing compounds found were alkanephos-phonic acids. Spurred on by these results, de Graaf et al. (1995) irradiated mixtures of o-phosphorous acid in the presence of formaldehyde, primary alcohols or acetone with UV light (low pressure Hg lamp, 254 nm with a 185-nm component) and obtained phosphonic acids, including hydroxymethyl and hydroxyethyl phosphonic acids, which had been found in the Murchison meteorite. Alkanephosphonic acids can be derived from phosphorous acid, with a P-H bond being replaced by a P-C bond. 

One way to create a carbon-carbon bond is to react a Grignard reagent with a carbonyl compound. The result of this reaction is an alcohol derived from an aldehyde. Formaldehyde gives a primary alcohol, but any other aldehyde gives a secondary alcohol. Ketones and esters both react to form tertiary alcohols. 

Like Grignard reagents, organolithium compounds react with formaldehyde to produce a primary alcohol. Figure 14-14 illustrates the reaction of an organolithium reagent with formaldehyde. 

Grignard reagents, organolithium compounds, and sodium alkynides react with formaldehyde to produce primary alcohols, all other aldehydes to produce secondary alcohols, and ketones to produce tertiary alcohols. 

These oxidations take place with most small primary alcohols. Unfortunately, the oxidation products of some other alcohols are more toxic than acetic acid. Methanol is oxidized first to formaldehyde and then to formic acid. Both of these compounds are more toxic than methanol itself. 

The consumption of six moles of periodic acid by streptamine without the liberation of formaldehyde showed the absence of primary alcohol groups. This observation along with the fact that analytical data on several salts of streptidine showed it to have two hydrogen atoms less than the number required for a saturated acyclic compound (bromine water, infrared and ultraviolet absorption spectra gave no indication of... 

The reactions of enolates bearing chiral auxiliaries with formaldehyde or symmetrical ketones can be stereoselective. After removal of the auxiliary, nonra-cemic primary or tertiary alcohols are obtained. The reaction of lithium enolates of Schollkopfs lactim ethers 1.114 with symmetrical carbonyl compounds are highly stereoselective, as are the reactions of enolates of Seebach s imidazolidinone S.39 (R = Ph). In both cases, the enolate reacts from its least hindered face [154, 261] (Figure 6.11). After acidic hydrolysis, P-hydroxy-a-aminoacids are obtained with a high enantiomeric excess. However, when R = H, some unwanted epimerization can take place. 

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