Aqueous formaldehyde

Only half of the aldehyde is reduced to the alcohol, the other half being oxidised to the acid. By using a slight excess (say, 1 -3 mols) of aqueous formaldehyde, practically the whole of the aromatic aldehyde is converted into the alcohol the formaldehyde Is simultaneously oxidised to formic acid. This is sometimes termed a crossed Cannizzaro reaction. The example given is ... 

Dimethylaminomethylindole (gramine). Cool 42 5 ml. of aqueous methylamine solution (5 2N ca. 25 per cent, w/v) contained in an 100 ml. flask in an ice bath, add 30 g. of cold acetic acid, followed by 17 -2 g. of cold, 37 per cent, aqueous formaldehyde solution. Pour the solution on to 23 -4 g. of indole use 10 ml. of water to rinse out the flask. Allow the mixture to warm up to room temperature, with occasional shaking as the indole dissolves. Keep the solution at 30-40° overnight and then pour it, with vigorous stirring, into a solution of 40 g. of potassium hydroxide in 300 ml. of water crystals separate. Cool in an ice bath for 2 hours, collect the crystalline solid by suction flltration, wash with three 50 ml. portions of cold water, and dry to constant weight at 50°. The yield of gramine is 34 g. this is quite suitable for conversion into 3-indoleacetic acid. The pure compound may be obtained by recrystaUisation from acetone-hexane m.p. 133-134°. 

The tetramethylol derivative of DABT, prepared by reaction of DABT with alkaline aqueous formaldehyde, polymerized readily on cotton. It imparted excellent flame retardancy, very durable to laundering with carbonate- or phosphate-based detergents as well as to hypochlorite bleach. This was accomphshed at low add-on without use of phosphoms compounds or antimony(III) oxide (75—77). 

Under neutral or slightly alkaline conditions, only the unstable hemiformal (CH O—CH2OH, methoxymethan0I) is produced. Alpha-chloromethyl ether is synthesized from aqueous formaldehyde, methanol, and hydrogen chloride (54). However, under anhydrous conditions, a carcinogenic by-product, bis(chloromethyl)ether is also formed (55). 

Hydrogen cyanide reacts with aqueous formaldehyde in the presence of bases to produce glyconitnle [107-16-4] (56,57) ... 

Aqueous formaldehyde is corrosive to carbon steel, but formaldehyde in the vapor phase is not. AH parts of the manufacturing equipment exposed to hot formaldehyde solutions must be a corrosion-resistant alloy such as type-316 stainless steel. Theoretically, the reactor and upstream equipment can be carbon steel, but in practice alloys are required in this part of the plant to protect the sensitive silver catalyst from metal contamination. 

Hexamethylenetetramine. Pure hexamethylenetetramine [100-97-0] (also called hexamine and HMTA) is a colorless, odorless, crystalline sohd of adamantane-like stmcture (141). It sublimes with decomposition at >200° C but does not melt. Its solubiUty in water varies Htde with temperature, and at 25°C it is 46.5% in the saturated solution. It is a weak monobase aqueous solutions are in the pH 8—8.5 range (142). Hexamethylenetetramine is readily prepared by treating aqueous formaldehyde with ammonia followed by evaporation and crystallisation of the soHd product. The reaction is fast and essentially quantitative (142). 

Formaldehyde—Alcohol Solutions. These solutions are blends of concentrated aqueous formaldehyde, the alcohol, and the hemiacetal. Methanol decreases the average molecular weight of formaldehyde oligomers by formation of lower molecular weight hemiacetals. These solutions are used to produce urea and melamine resins the alcohol can act as the resin solvent and as a reactant. The low water content can improve reactivity and reduce waste disposal and losses. Typical specifications for commercially available products are shown in Table 7 (117). 

Trioxane and Tetraoxane. The cycHc symmetrical trimer of formaldehyde, trioxane [110-88-3] is prepared by acid-catalyzed Hquid- or vapor-phase processes (147—151). It is a colorless crystalline soHd that bods at 114.5°C and melts at 61—62°C (17,152). The heats of formation are — 176.9 kJ/mol (—42.28 kcal/mol) from monomeric formaldehyde and —88.7 kJ/mol (—21.19 kcal/mol) from 60% aqueous formaldehyde. It can be produced by continuous distillation of 60% aqueous formaldehyde containing 2—5% sulfuric acid. Trioxane is extracted from the distillate with benzene or methylene chloride and recovered by distillation (153) or crystallization (154). It is mainly used for the production of acetal resins (qv). 

The nitro alcohols available in commercial quantities are manufactured by the condensation of nitroparaffins with formaldehyde [50-00-0]. These condensations are equiUbrium reactions, and potential exists for the formation of polymeric materials. Therefore, reaction conditions, eg, reaction time, temperature, mole ratio of the reactants, catalyst level, and catalyst removal, must be carefully controlled in order to obtain the desired nitro alcohol in good yield (6). Paraformaldehyde can be used in place of aqueous formaldehyde. A wide variety of basic catalysts, including amines, quaternary ammonium hydroxides, and inorganic hydroxides and carbonates, can be used. After completion of the reaction, the reaction mixture must be made acidic, either by addition of mineral acid or by removal of base by an ion-exchange resin in order to prevent reversal of the reaction during the isolation of the nitro alcohol (see Ion exchange). 

Aqueous Formaldehyde. Water solutions of formaldehyde consist mainly of telomers of methylene glycol having <100 ppm of the formaldehyde as CH2O (5). Alcohols form hemiformals with aqueous formaldehyde according to the following, where n = 1,2,3, etc. 

Aqueous formaldehyde, known as formalin, is usually 37 wt % formaldehyde, though more concentrated solutions are available. Formalin is the general-purpose formaldehyde of commerce suppHed unstabiLized or methanol-stabilized. The latter may be stored at room temperature without precipitation of soHd formaldehyde polymers because it contains 5 —10% methyl alcohol. The uiiinhibited type must be maintained at a temperature of at least 32°C to prevent the separation of soHd formaldehyde polymers. Large quantities are often suppHed in more concentrated solutions. Formalin at 44,... 

Precise coatrol of the course, speed, and extent of the reaction is essential for successful manufacture. Important factors are mole ratio of reactants catalyst (pH of reaction mixture) and reaction time and temperature. Amino resias are usually made by a batch process. The formaldehyde and other reactants are charged to a kettie, the pH adjusted, and the charge heated. Often the pH of the formaldehyde is adjusted before a dding the other reactants. Aqueous formaldehyde is most convenient to handle and lowest ia cost. 

A fiactionating column is lequked foi the removal of ammonia and recycle of ethylenediamine. The molten product (mp 133°C) is then mn into ice water to give a solution that is methylolated with 37% aqueous formaldehyde. 

Temperatures in excess of 140°C are required to complete the reaction and pressurized equipment is used for alcohols boiling below this temperature provision must be made for venting ammonia without loss of alcohol. The reaction is straightforward and, ia the case of the monomethyl ether of ethylene glycol [109-86-4] can be carried out at atmospheric pressure usiag stoichiometric quantities of urea and alcohol (45). Methylolation with aqueous formaldehyde is carried out at 70—90°C under alkaline conditions. The excess formaldehyde needed for complete dimethylolation remains ia the resia and prevents more extensive usage because of formaldehyde odor problems ia the mill. 

An industrially important example is the condensation of a- (2) or y-picoline (4) with aqueous formaldehyde to form the corresponding ethanolpyridines, 2-ethanolpyridine [104-74-2] (22) and 4-ethanolpyridine [5344-27-4] respectively, followed by dehydration of the alcohols to give 2- (23) or 4-vinylpyridine. 

Side-Chain Derivatization. Reaction of thiophene with aqueous formaldehyde solution in concentrated hydrochloric acid gives 2-chloromethylthiophene [765-50-4]. This relatively unstable, lachrymatory material has been used as a commercial source of further derivatives such as 2-thiopheneacetonitrile [20893-30-5] and 2-thiopheneacetic acid [1918-77-0] (24). Similar derivatives can be obtained by peroxide, or light-catalyzed (25) halogenation of methylthiophenes, eg, Ai-bromosuccinimide/benzoylperoxide on 2-, and 3-methylthiophenes gives the corresponding bromomethylthiophenes. 

Cyanuric acid readily dissolves in aqueous formaldehyde forming tris(hydroxymethyl)isocyanurate [10471-40-6] (THMIC) which can be isolated by evaporation (11). THMIC in turn reacts with acetic anhydride to yield tris(acetoxymethyl)isocyanurate [54635-07-3], either thionyl chloride or phosphoms pentachloride to give tris(chloromethyl)isocyanurate [63579-00-0], and phenyl isocyanate in pyridine to yield tris(A/-phenylcarbamoxymethyl) isocyanurate [21253-39-4] in 87% yield (65). Reaction of CA with paraformaldehyde and 2,6-dicyclohexylphenol yields... 

Other options for the purification of CA include dissolution in hot water, aqueous ammonia, aqueous formaldehyde, or hot dimethylformamide followed by filtration to remove most of the impurities. The CA is recoverable by cooling the aqueous solution (84), acidifying the ammonium hydroxide solution (85), or cooling the dimethylform amide solution with further precipitation of CA by addition of carbon tetrachloride (86). Sodium hydroxide addition precipitates monosodium cyanurate from the formaldehyde solution (87). 

To 500 g. (3.85 moles) of freshly distilled ethyl acetoacetate in a i-l. flask set in ice and well cooled, are added 152 g. (2.0 moles) of 40 per cent aqueous formaldehyde solution and 20-25 drops of diethylamine. The flask and contents are kept cold for six hours and are then allowed to stand at room temperature for forty to forty-five hours. At the end of this time two layers are present, a lower oily layer and an upper aqueous layer. The layers are separated, and the aqueous layer is extracted with 50 cc. of ether. The ether solution is added to the oily layer, and the resulting solution is dried over 30 g. of calcium chloride. The ether is then removed by distillation on a steam bath. The residue, amounting to approximately 500 g., is diluted with an equal volume of alcohol and is thoroughly cooled in an ice bath. Ammonia is then passed into the mixture until the solution is saturated. This requires from four to eight hours, and during this time the flask is kept packed in ice. The ammoniacal alcoholic solution is allowed to stand at room temperature for forty to forty-five hours. Most of the alcohol is now evaporated the residue is cooled, and the solid i,4-dihydro-3,5-dicarbethoxy-2,6-dimethylpyridine is removed from the remaining alcohol on a suction filter. The dried ester melts at 175-180 and amounts to 4ro-435 g. (84-89 per cent of the theoretical amount). 

Commercial aqueous formaldehyde solution, containing about 8% of methanol, was used. 

Commercial aqueous formaldehyde solution containing 8% methanol was used. Formaldehyde is needed in excess otherwise the yield is considerably diminished. 

The amine, under the name N,N,N, N -tetramethyl-methylenediamine, may be purchased from Ames Laboratories, South Norwalk, Connecticut. The checkers prepared it by the following procedure. A solution of 60.7 g. (0.75 mole) of 37% aqueous formaldehyde solution is placed in an 800-ml. beaker equipped with a mechanical stirrer and thermometer, and cooled in an ice bath. Two hundred seventy-one grams (1.50 moles) of a 25% aqueous solution of dimethylamine is added to this solution at a rate such that the reaction temperature is kept below 15°. The solution is stirred for 30 minutes after the addition is complete, and potassium hydroxide pellets (approximately 150 g.) are added in portions until the reaction mixture separates into two layers. The upper layer is separated, dried over potassium hydroxide pellets overnight, and distilled to give 59 -64 g. (77-83%) of bis(dimcthylamin())mclliane, b.p. 83 84°. ... 

One of the most extensively investigated groups of 1,3-oxazine derivatives is the 5-nitro derivatives of tetrahydro-l,3-oxazine. They were first prepared from 1-nitropropane, aqueous formaldehyde, and ammonia by Hirst et and independently by Senkus from other primary nitroparaffins, formaldehyde, and primary amines. Numerous compounds of the general formula (6) were later prepared from primary nitroparaffins. " ... 

The formation of complex mixtures of products by a Prins reaction can be a problem. An example is the reaction of aqueous formaldehyde with cyclohexene 8 under acid catalysis ... 

Meerwein s Ester (9) Dimethyl malonate (13.2 g, 0.4 mole) and 6 g of 40 % aqueous formaldehyde solution are mixed in an Erlenmeyer flask and cooled to 0° in an ice bath. To the mixture is added 0.3 g of piperidine and enough ethanol to produce a homogeneous solution. The solution is allowed to stand at 0° for 12 hours, at room temperature for 24 hours, and at 35 0° for 48 hours. The reaction product is washed with water (50 ml) followed by dilute sulfuric acid, then dried (sodium sulfate). Unreacted malonic ester is distilled off under vacuum leaving a residue of about 12.5 g, which contains methylenemalonic ester, methylenebismalonic ester, and hexacarbomethoxypentane. 

The reductive alkylation of aromatic nitro compounds using H +Pd/G in the presence of 40% aqueous formaldehyde gives directly dimethylamino derivatives in good yield (Tq. 6.43. ... 

In a synthesis of minocycline, interesting use was made of a reductive alkylation of a nitro function, accompanied by loss of a diazonium group. The sequence provides a clever way of utilizing the unwanted 9-nitro isomer that arises from nitration of 6-demethyl-6-deoxytetracycline (//). When di-azotization was complete, urea and 40% aqueous formaldehyde were added, and the entire solution was mixed with 10% palladium-on-carbon and reduced under hydrogen. No further use of this combined reaction seems to have been made. 

Forty-seven grams (0.5 mol) of phenol, 80 mL of 37 wt % aqueous formaldehyde (1.0 mol), and 100 mol of 4 A NaOH were charged to a flask equipped with a reflux condenser and mechanical stirrer. The reaction mixture was stirred at room temperature for 16 h, then heated on a steam bath for 1 h. The mixture was cooled and the pH adjusted to 7.0. The aqueous layer was decanted from the viscous brown liquid product, the wet organic phase was taken up in 500 mL of acetone and dried over anhydrous MgSCL, then over molecular sieves. The dried acetone product solution was filtered and evaporated to yield a water-free light brown syrup. 

Simple imines are poor dienophiles and must be activated by protonation or by attaching an electron-withdrawing group to the nitrogen atom. Scheme 6.10 illustrates the Diels-Alder reactions of benzyliminium ion 25, generated in situ from an aqueous solution of benzylamine hydrochloride and commercial aqueous formaldehyde, with methylsubstituted 1,3-butadienes [22]. This aqueous Diels-Alder reaction combines three components (an aldehyde, an amine... 

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