Primary compounds with formaldehyde

MANNICH REACTION. Reaction ol active methylene compounds with formaldehyde and ammonia of primary or secondary amines to give fj-aminocarbonyl compounds. 

Primary phosphines can add to carbon-carbon (or other unsaturated double bonds) under a variety of conditions to give new phosphorus(III) compounds.41 Furthermore, another reaction of primary (and secondary) phosphines is their ready conversion into air-stable, crystalline hydro-xymethylphosphonium salts by reaction with an excess of formaldehyde and hydrochloric acid.42 These can subsequently be used in the synthesis of new (hydroxymethyl)phosphines. Alternatively, formylation of primary phosphines with formaldehyde affords functionalized tertiary phosphines, which often display excellent water solubility (e.g., H2P(CH2)2PH2 (21) gives (HOCH2)2P(CH2)2P(CH2OH)2 (30)).33... 

Direct IV-oxidation of these heterocycles invariably fails (see Section 3.02.7.2.8), making ring synthetic methods the only viable alternative <93CHE127>. Although there has been considerable interest in the chemistry of compounds of this type, there are no new synthetic approaches of a general nature. The most common approach is to react a-oximinoketones with aldehydes and primary amines. With formaldehyde, however, the 2-unsubstituted 1-oxides rearrange to 2-imi-dazolones. Variations on this theme allow synthesis of 1-hydroxyimidazole 3-oxides. Thus, treatment of an a-dicarbonyl compound with an aldehyde and hydroxylamine, or reaction of the aldehyde oxime or aldehyde with a 1,2-dioxime are common approaches <898773 >. Similarly, a-hydroxyamino-... 

Mannich reaction.2 This reaction involves the condensation of an active hydrogen compound with formaldehyde and ammonia or a primary or secondary amine (usually as the hydrochloride) ... 

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. 

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. 

Benzoxazines are heterocyclic compounds obtained from reaction of phenols, primary amines, and formaldehyde.98,99 As described previously, they are key reaction intermediates in the HMTA-novolac cure reaction.40,43 Crosslinking benzoxazine monomers at high temperatures gives rise to void-free networks with high Tgs, excellent heat resistance, good flame retardance, and low smoke toxicity.100 As in HMTA-cured novolac networks, further structural rearrangement may occur at higher temperatures. 

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 ... 

Acidic compounds with N—H bonds such as amides, carbamates, and hydan-toins, may be transformed to /V-rnannich bases to form oral prodrugs [2], These prodrugs are generally made by reacting an amide, carbamate, or hydantoin with formaldehyde and a primary or secondary aliphatic or aromatic amine (Fig. 4). The (V-mannich prodrugs tend to have better physicochemical properties than the parent compounds. The derivatives may have increased water solubility, dissolution rate, and/or lipophilicity. 

Pyrido[2,l-4][l,3,5]thiadiazine derivatives 175 were prepared from pyridine precursor treatment of iV-iucthylruor-pholinium salt of pyridine thiolates 174 with primary amines and formaldehyde afforded compounds 175 (Equation 27) <2003DOC92>. 

Aminomethano destannylotion bishomoallyl amines. Methyleneimmonium trifluoroacetates, generated in situ from primary amines and formaldehyde, react with allyltrialkyltin compounds to form bishomoallylic amines in high yield Example ... 

Many of the nitronate salts of polynitroaliphatic compounds, particularly salts of gem-nitronitronates, exhibit properties similar to known primary explosives. Consequently, the storage of such salts is highly dangerous. Treatment of these nitronate salts with formaldehyde yields the corresponding methylol derivative via the Henry condensation. These methylol... 

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. 

A Mannich reaction is the reaction of formaldehyde with a primary or secondary amine and a compound with an active hydrogen atom. The product, an amine with a y-carbonyl, is called a Mannich base, useful in a number of synthesis reactions. An example is in Figure 15-23, and the mechanism is in Figure 15-24. 

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 first step of the synthesis of the new ionic liquids 26 involved the selective protection of the OH-3 to give the monobenzyl ether 21 in 56% yield (Scheme 6). Then the exo OH group at position 6 was quantitatively activated as benzenesulfo-nate and treated with an excess of three primary amines in a sealed tube at 160°C to afford the corresponding secondary amino derivatives 23a-C in good yield. The latter compounds were transformed into the tertiary amines 24a-C by reaction with formaldehyde in formic acid (EschweUer-Clark reaction). 

Regioselective aminomethylation and subsequent cyclization of methyl 2,4-dihydroxybenzoate 517 was accomplished through a Mannich reaction with formaldehyde and primary amines in methanol to yield 3-substituted-3,4-dihydro-2/7-l,3-benzoxazine derivatives 518 (Equation 60). Simultaneous mixing of the reactants resulted in poor yields, but good yields were achieved by the pretreatment of paraformaldehye with a primary amine to form a Schiff base, followed by the addition of compound 517 <2001TL7273>. 

Hydroxy-l-nitrohydrazones (809) react with primary amines and formaldehyde to give 2,3,4,5-tetrahydro-l,2,4-triazines (810) (64MI21901), and similar compounds (812) can be obtained from the reaction of aldehyde hydrazones (811) with primary amines and aldehydes (74KGS425, 75KGS1290, 74UKZ1220). 

A third method for the preparation of 2,3,4,5-tetrahydro-l,2,4-triazines is to react hydrazines with primary amines and formaldehyde (78HC(33)189, p. 630). The first step here is probably the formation of a formaldehyde hydrazone (811 R6 = H) which reacts with another molecule of formaldehyde to give compound (813), the structure of which is similar to (809). 

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

In order to differentiate between the two formaldehyde forming reactions in the case of propylene, reaction (6), attack on CH3 group, and (8), attack on CH2 group of the double bond, Avramenko and Kolesnikova carried out experiments with 1,3-butadiene, which leaves only the latter alternative. Quantitative analyses were carried out only for the carbonyl compounds and the acids. Carbonyl compounds consisted of acrolein, formaldehyde, and higher aldehydes. Acrolein appeared to be a primary product, and formaldehyde and acid secondary ( quadratic ) products. The postulated primary reaction was... 

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. 

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