Reactions of formaldehyde

Figure 3-12. The reaction of formaldehyde v matrix representation of this reaction.

This particular representation makes it easy to visualize formaldehyde as a step-growth monomer of functionality 2. Our principal interest is in the reactions of formaldehyde with the active hydrogens in phenol, urea, and melamine, compounds [II] [IV], respectively ... 

Reactions with Ammonia and Amines. Acetaldehyde readily adds ammonia to form acetaldehyde—ammonia. Diethyl amine [109-87-7] is obtained when acetaldehyde is added to a saturated aqueous or alcohoHc solution of ammonia and the mixture is heated to 50—75°C in the presence of a nickel catalyst and hydrogen at 1.2 MPa (12 atm). Pyridine [110-86-1] and pyridine derivatives are made from paraldehyde and aqueous ammonia in the presence of a catalyst at elevated temperatures (62) acetaldehyde may also be used but the yields of pyridine are generally lower than when paraldehyde is the starting material. The vapor-phase reaction of formaldehyde, acetaldehyde, and ammonia at 360°C over oxide catalyst was studied a 49% yield of pyridine and picolines was obtained using an activated siHca—alumina catalyst (63). Brown polymers result when acetaldehyde reacts with ammonia or amines at a pH of 6—7 and temperature of 3—25°C (64). Primary amines and acetaldehyde condense to give Schiff bases CH2CH=NR. The Schiff base reverts to the starting materials in the presence of acids. 

Sulfomethylation. The reaction of formaldehyde and sodium bisulfite [7631-90-5] with polyacrylamide under alkaline conditions to produce sulfomethylated polyacrylamides has been known for many years (44—46). A more recent pubHcation (47) suggests, however, that the expected sulfomethyl substitution is not obtained under the previously described strongly alkaline conditions of pH 10—12. This C-nmr study indicates that hydrolysis of polyacrylamide occurs and the resulting ammonia reacts with the NaHSO and formaldehyde. A recent patent claims a new high pressure, high temperature process at slightly acid pH for preparation of sulfomethylated polyacrylamide (48). 

Pentaerythritol is produced by reaction of formaldehyde [50-00-0] and acetaldehyde [75-07-0] in the presence of a basic catalyst, generally an alkah or alkaline-earth hydroxide. Reaction proceeds by aldol addition to the carbon adjacent to the hydroxyl on the acetaldehyde. The pentaerythrose [3818-32-4] so produced is converted to pentaerythritol by a crossed Cannizzaro reaction using formaldehyde. All reaction steps are reversible except the last, which allows completion of the reaction and high yield industrial production. 

Tetrakis(hydroxymethyl)phosphonium Salts. The reaction of formaldehyde (qv) and phosphine in aqueous hydrochloric or sulfuric acid yields tetrakis-(hydroxymethyl)phosphonium chloride [124-62-1/, Albright Wilson s Retardol C, or the sulfate [55566-30-8] (Retardol S), (C4H 2C4P)2SO [55566-30-8]. 

Mono- and dimethylol derivatives are made by reaction of formaldehyde with unsubstituted amides. Dimethylolurea, an item of commercial importance and an intermediate in urea—formaldehyde resins, is formed in high yield under controlled conditions (62) ... 

Reaction of formaldehyde, methanol, acetaldehyde, and ammonia over a siUca alumina catalyst at 500°C gives pyridine [110-86-1] and 3-picoline... 

The main processes for the manufacture of hydroxybenzaldehydes are based on phenol. The most widely used process is the saligenin process. Saligenin (2-hydroxybenzyl alcohol [90-01-7]) and 4-hydroxybenzyl alcohol [623-05-2] are produced from base-catalyzed reaction of formaldehyde with phenol (35). Air oxidation of saligenin over a suitable catalyst such as platinium or palladium produces sahcylaldehyde (62). 

Manufacture, Processing, and Economic Aspects. Hydroxyacetic acid is produced commercially in the United States as an iatermediate by the reaction of formaldehyde with carbon monoxide and water. 

Other methods of production iaclude hydrolysis of glycolonittile [107-16 ] with an acid (eg, H PO or H2SO2) having a piC of about 1.5—2.5 at temperatures between 100—150°C glycolonittile produced by reaction of formaldehyde with hydrogen cyanide recovery from sugar juices and hydrolysis of monohalogenated acetic acid. None of these has been commercially and economically attractive. 

Other Nitrogen Compounds. The basis of the sophisticated nitrogen compounds Hsted in Table 10 is the reaction of formaldehyde with amino compounds. A significant amount of Hterature details investigation of the mechanism of action, particularly whether or not the antimicrobial activity depends on decomposition to formaldehyde (40—42). These compounds tend to have substantial water solubiUty and are more effective against bacteria than fungi and yeasts. Key markets for these compounds are metalworking fluids, cosmetics, and in-can preservation of paints (see Alkanolamines Amines, fatty amines). 

Fig. 1. Reaction of formaldehyde with monoethanolamine. If two moles of monoethanolamine react with three moles of formaldehyde, the bisoxazohdine is the only product isolated. A 1 1 mole ratio of monoethanolamine to formaldehyde produces a mixture of the triazine and the bisoxazohdine.

Most amino lesins are based on the reaction of formaldehyde [50-00-0J with urea [57-13-6J or melamine [108-78-1]... 

With Formaldehyde. The sulfuric acid cataly2ed reaction of formaldehyde [50-00-0] with carbon monoxide and water to glycoHc acid [79-14-1] at 473 K and 70 MPa (700 atm) pressure was the first step in an early process to manufacture ethylene glycol [107-21-1]. A patent (58) has described the use of Hquid hydrogen fluoride as catalyst, enabling the reaction to be carried out at 298 K and 7 MPa (70 atm) (eq. 18). 

Manufacturing and Processing. Urea—formaldehyde fertilizers are prepared from the reaction of formaldehyde with excess urea (U/E mole ratio 1). The reaction proceeds in two steps. In Step 1, urea and formaldehyde are combined to form monomethylol [1000-82-4] and dimethylolurea [140-95-4] intermediates. 

Direct reaction of formaldehyde cyanohydrin and ethylenediamine in the presence of a sulfuric acid catalyst gives ethylenediarninetetraacetonitrile [5766-67-6], hydrolysis of which leads to ethylenediarninetetraacetic acid [60-00-4] (EDTA), a widely used sequestering agent (26). 

Nitrilotriacetonitrile [628-87-5], N(CH2CN)2, a precursor to nitrilotriacetic acid [139-13-9], N(CH2COOH)2, can be prepared from the reaction of formaldehyde cyanohydrin with ammonia (26). Formaldehyde cyanohydrin is also used as an intermediate in pharmaceutical production. Commercial formaldehyde cyanohydrin is available as a 70% aqueous solution stabiLhed by phosphoric acid. 

MO (STO-3G) calculations on the gas-phase hydration reaction of formaldehyde suggest a concerted process involving two water molecules as a low-energy mechanism for hydration. 

The manufacture of alkyl cyanoacrylate monomers, 1, involves the Knoevenagel reaction of formaldehyde, 2, with an alkyl cyanoacetate, 3, and a base, such as a secondary amine, as the catalyst, shown in Eq. 1. 

The transition-state structure of the hetero-Diels-Alder reaction is generally found to be unsymmetrical. Houk et al. have for the reaction of formaldehyde with 1,3-butadiene calculated the C-C and C-0 bond lengths to be 2.133 A and 1.998 A, respectively, in the transition state using ab-initio calculations shown in Fig. 8.12 [25 bj. The reaction of formaldimine follows the same trend for the transition-state structure. 

The hetero-Diels-Alder reaction of formaldehyde with 1,3-butadiene has been investigated with the formaldehyde oxygen atom coordinated to BH3 as a model for a Lewis acid [25 bj. Two transition states were located, one with BH3 exo, and one endo, relative to the diene. The former has the lowest energy and the calculated transition-state structure is much less symmetrical than for the uncatalyzed reaction shown in Fig. 8.12. The C-C bond length is calculated to be 0.42 A longer, while the C-0 bond length is 0.23 A shorter, compared to the uncatalyzed reac-... 

Fig. 8.12 Calculated transition-state structure for the hetero-Diels-Alder reaction of formaldehyde with butadiene [25 bj...

An alternative route to acrylic esters is via a (3-propiolactone intermediate. The lactone is obtained by the reaction of formaldehyde and ketene, a dehydration product of acetic acid ... 

Acid catalysts, such as metal oxides and sulfonic acids, generally catalyze condensation polymerizations. However, some condensation polymers form under alkaline conditions. For example, the reaction of formaldehyde with phenol under alkaline conditions produces methy-lolphenols, which further condense to a thermosetting polymer. 

These resins are prepared by an addition reaction of formaldehyde with either phenols, urea or melamine to prepare an intermediate such as the following ... 

Among the more effective conditions for reaction of formaldehyde with a-methylstyrenes is BF3 in combination with 4A molecular sieves.37... 

Pentaerythritol is made commercially by the reaction of formaldehyde and acetaldehyde in the presence of alkali. It can be nitrated by adding it to strong nitric acid at temperatures below about 30°C. An excess of nitric... 

Figure 3.1 Two essential steps of chemical reaction of formaldehyde (HCHO) with nucleic acid exemplified by adenine that are similar to formaldehyde-protein reactions, (a) Addition reaction as the first step, resulting in a methylol derivative, methylol adenylic acid (b) Second step is a condensation reaction, a stable product methylene-bis-adenylic acid is derived between the methylol derivative and another adenine. Reproduced with permission from Shi et al.,AIMM 2001 9 107-116. 

In general, the mechanism of heat and alkaline solution for DNA extraction may be based upon a hypothesis, previously proposed for the AR technique.32 Strong alkaline solution may denature and hydrolyze proteins, resulting in breaking cell and nuclear membranes as well as disrupting cross-linkages due to formalin fixation. It is no surprise to observe the similarity between retrieval of nucleic acid and retrieval of protein (antigen) based on a similar chemical reaction of formaldehyde with these two kinds of macromolecules (Fig. 3.1).15"19... 

McGhee JD, von Hippel PH. Formaldehyde as a probe of DNA structure. 4. Mechanism of the initial reaction of formaldehyde with DNA. Biochemistry 1977 16 3276-3293. 

Fraenkel-Conrat H, Brandon BA, Olcott HS. The reaction of formaldehyde with proteins. IV. Participation of indole groups. /. Biol. Chem. 1947 168 99-118. 

Fraenkel-Conrat H, Olcott HS. Reaction of formaldehyde with proteins. VI. Cross-linking of amino groups with phenol, imidazole, or indole groups. J. Biol. Chem. 1948 174 827-843. 

French D, Edsall JT.The reactions of formaldehyde with amino acids and proteins. Adv. Protein Chem. 1945 2 277-335. 

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