Formaldehyde dehydration

Hydroxycoumarin can be considered as an enol tautomer of a 1,3-dicarbonyl compound conjugation with the aromatic ring favours the enol tautomer. This now exposes its potential as a nucleophile. Whilst we may begin to consider enolate anion chemistry, no strong base is required and we may formulate a mechanism in which the enol acts as the nucleophile, in a simple aldol reaction with formaldehyde. Dehydration follows and produces an unsaturated ketone, which then becomes the electrophile in a Michael reaction (see Section 10.10). The nucleophile is a second molecule of 4-hydroxycoumarin. 

Figure 7-32 Micrograph of a mouse embryo fibroblast was obtained using indirect immunofluorescence techniques.313 The cells were fixed with formaldehyde, dehydrated, and treated with antibodies (formed in a rabbit) to microtubule protein. The cells were then treated with fluorescent goat antibodies to rabbit /-globulins (see Chapter 31) and the photograph was taken by fluorescent light emission. Courtesy of Klaus Weber.

Glyoxal can be formed by oxidation of glycolaldehyde (e.g., in Scheme 2.5), but it can also be formed by autoxidation of unsaturated fats and by enzymic degradation of serine.60 2-Oxopropanal can be obtained by retroaldolisation of 1- and 3-deoxyglucosone or by hydrolysis of diacetylformoin (see Scheme 2.5). Butanedione can also be derived from diacetylformoin, but by reduction, dehydration, and hydrolysis (see Scheme 2.5). 2,3-Pentanedione can be formed from butanedione by aldol reaction with formaldehyde, dehydration, and reduction or by aldol condensation of hydroxyacetone and acetaldehyde, followed by dehydration. 

Dehydration of 2 2 3 4 4 pentamethyl 3 pentanol gave two alkenes A and B Ozonolysis of the lower boiling alkene A gave formaldehyde (H2C=0) and 2 2 4 4 tetramethyl 3 pentanone Ozonolysis of B gave formaldehyde and 3 3 4 4 tetramethyl 2 pentanone Identify A and B and suggest an explanation for the formation of B in the dehydration reaction... 

Vapor-Phase Condensations of Acetic Acid or Esters with Formaldehyde. Addition of a methylol group to the a-carbon of acetic acid or esters, foUowed by dehydration, gives the acrylates. 

Other examples are glycine — formaldehyde, alanine — acetaldehyde, valine — isobutyraldehyde, phenylalanine — phenylacetaldehyde, and methionine — methional (106). Products such as dried skim milk, dried eggs, and dehydrated vegetables and fmits are particularly susceptible to deteriorative flavor changes ascribed to this reaction (Table 10). 

Methyl vinyl ketone can be produced by the reactions of acetone and formaldehyde to form 4-hydroxy-2-butanone, followed by dehydration to the product (267,268). Methyl vinyl ketone can also be produced by the Mannich reaction of acetone, formaldehyde, and diethylamine (269). Preparation via the oxidation of saturated alcohols or ketones such as 2-butanol and methyl ethyl ketone is also known (270), and older patents report the synthesis of methyl vinyl ketone by the hydration of vinylacetylene (271,272). 

On dehydration, nitro alcohols yield nitro-olefins. The ester of the nitro alcohol is treated with caustic or is refluxed with a reagent, eg, phthaUc anhydride or phosphoms pentoxide. A mil der method involves the use of methane sulfonyl chloride to transform the hydroxyl into a better leaving group. Yields up to 80% after a reaction time of 15 min at 0°C have been reported (5). In aqueous solution, nitro alcohols decompose at pH 7.0 with the formation of formaldehyde. One mole of formaldehyde is released per mole of monohydric nitro alcohol, and two moles of formaldehyde are released by the nitrodiols. However, 2-hydroxymethyl-2-nitro-l,3-propanediol gives only two moles of formaldehyde instead of the expected three moles. The rate of release of formaldehyde increases with the pH or the temperature or both. 

The typical acid catalysts used for novolak resins are sulfuric acid, sulfonic acid, oxaUc acid, or occasionally phosphoric acid. Hydrochloric acid, although once widely used, has been abandoned because of the possible formation of toxic chloromethyl ether by-products. The type of acid catalyst used and reaction conditions affect resin stmcture and properties. For example, oxaUc acid, used for resins chosen for electrical appHcations, decomposes into volatile by-products at elevated processing temperatures. OxaUc acid-cataly2ed novolaks contain small amounts (1—2% of the original formaldehyde) of ben2odioxanes formed by the cycli2ation and dehydration of the ben2yl alcohol hemiformal intermediates. 

Resoles. Like the novolak processes, a typical resole process consists of reaction, dehydration, and finishing. Phenol and formaldehyde solution are added all at once to the reactor at a molar ratio of formaldehyde to phenol of 1.2—3.0 1. Catalyst is added and the pH is checked and adjusted if necessary. The catalyst concentration can range from 1—5% for NaOH, 3—6% for Ba(OH)2, and 6—12% for hexa. A reaction temperature of 80—95°C is used with vacuum-reflux control. The high concentration of water and lower enthalpy compared to novolaks allows better exotherm control. In the reaction phase, the temperature is held at 80—90°C and vacuum-refluxing lasts from 1—3 h as determined in the development phase. SoHd resins and certain hquid resins are dehydrated as quickly as possible to prevent overreacting or gelation. The end point is found by manual determination of a specific hot-plate gel time, which decreases as the polymerization advances. Automation includes on-line viscosity measurement, gc, and gpc. 

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. 

As with resoles, we can use a three-phase model to discuss formation of a novolac. Whereas the resole is activated through the phenol, activation in novolacs occurs with protonation of the aldehyde as depicted in Scheme 12. The reader will note that the starting material for the methylolation has been depicted in hydrated form. The equilibrium level of dissolved formaldehyde gas in a 50% aqueous solution is on the order of one part in 10,000. Thus, the hydrated form is prevalent. Whereas protonation of the hydrate would be expected to promote dehydration, we do not mean to imply that the dehydrated cation is the primary reacting species, though it seems possible. 

The presence of unsaturation in the side chain is also compatible with antihistaminic activity. Mannich condensation of p-chloroacetophenone with formaldehyde and pyrollidine affords the amino ketone, 109. Reaction with an organometallic reagent from 2-bromopyridine gives 110. Dehydration leads to triproli-dine (111). ... 

Butadiene could also be obtained by the reaction of acetylene and formaldehyde in the vapor phase over a copper acetylide catalyst. The produced 1,4-butynediol is hydrogenated to 1,4-butanediol. Dehydration of 1,4-butanediol yields butadiene. 

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 ... 

Scheme L A mechanism for the formaldehyde catalyzed dehydration of p-hydroxynitrosamines.

Spherical microparticles are more difficult to manufacture and can be prepared by several methods. One method prepares silica hydrogel beads by emulsification of a silica sol in an immiscible organic liquid [20,21,24,25]. To promote gelling a silica hydrosol, prepared as before, is dispersed into small droplets in a iater immiscible liquid and the temperature, pH, and/or electrolyte concentration adjusted to promote solidification. Over time the liquid droplets become increasingly viscous and solidify as a coherent assembly of particles in bead form. The hydrogel beads are then dehydrated to porous, spherical, silica beads. An alternative approach is based on the agglutination of a silica sol by coacervation [25-27], Urea and formaldehyde are polymerized at low pH in the presence of colloidal silica. Coacervatec liquid... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

According to R. Brdicka and K. Vesely the carbonyl form of formaldehyde is reduced and the limiting kinetic current is given by the rate of the chemical volume reaction of dehydration. An analogous situation occurs for the equilibria among complexes, metal ions and complexing agents if the rates of complex formation and decomposition are insufficient to preserve the equilibrium. A simple example is the deposition of cadmium at a mercury electrode from its complex with nitrilotriacetic COO"... 

Inclusion of an acetylenic linkage as part of the side chain is apparently consistent with antidepressant activity. Reaction of propargyl magnesium bromide with dibenzocycloheptadieneone leads to carbinol 82. A Mannich reaction with formaldehyde and dimethylamine leads to 83 which, upon dehydration... 

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. 

RaitVK, Zhang Q,Fabris D,et al. Conversions of formaldehyde-modified 2 -deoxy-adenosine 5 -monophosphate in conditions modeling formalin-fixed tissue dehydration. I. Histochem. Cytochem. 2006 54 301-310. 

There have been no comprehensive studies of how exposure to ethanol, xylene, or paraffin affects proteins following their treatment with aqueous formaldehyde. However, in a related study, Rait et al.25 examined the effect of ethanol incubation on 2 -deoxyadenosine that had been treated with aqueous formaldehyde. Mass spectrometry revealed the presence of N6-ethoxymethyl adducts in addition to hydroxymethyl adducts. This lead to the suggestion that tissue dehydration can result in molecular dehydration, transforming hydroxymethyl groups into Schiff-bases. In such a scheme, the bulk anhydrous ethanol acts as a medium to effectively absorb the water of the... 

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