Formaldehyde equivalent

Prior to 1890, formaldehyde was not commercially available [2]. Thus the first phenol-formaldehyde resins were made using formaldehyde equivalents such as methylene diacetate or methylal [2,20]. The first true phenol-formaldehyde resin was made by Kleeberg at the direction of Emil Fisher in 1891 [2,21]. Saliginen (o-hydroxymethyl phenol) was recognized as a condensation product of phenol and formaldehyde in 1894 and was the subject of United States patents in 1894 and 1896 [22,23]. 

Scheme 2.12 shows some representative Mannich reactions. Entries 1 and 2 show the preparation of typical Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as l>is-(di methyl ami no)methane in Entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. lV,A-(Dimethyl)methylene ammonium iodide is commercially available and is known as Eschenmoser s salt.192 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.183 The reagent can be added to a solution of an enolate or enolate precursor, which permits the reaction to be carried out under nonacidic conditions. Entries 4 and 5 illustrate the preparation of Mannich bases using Eschenmoser s salt in reactions with preformed enolates. 

The reaction between acrylonitrile and formaldehyde (as paraformaldehyde or tri-oxane), under strong acid catalysis (usually sulphuric) and most often in presence of catalytic quantities of acetic anyhydride, to produce triacrylohexahydrotriazine, is inclined to violent exotherm after an induction period. The runaway can be uncontrollable on sub-molar scale. It may be due to acrylate polymerisation or to increasing reactivity of the formaldehyde equivalent due to progressive de-oligomerisation. Procedures claimed to prevent the risk have been described in the literature but do not seem reliable. 

Synthesis of isomeric chiral protected (63 )-6-amino-hexahydro-2,7-dioxopyrazolo[l,2- ]pyrazole-l-carboxylic acid 280 is shown in Scheme 36. Crude vinyl phosphonate 275, obtained by treatment of diethyl allyloxycarbonylmethyl-phosphonate with acetic anhydride and tetramethyl diaminomethane as a formaldehyde equivalent, was used in the Michael addition to chiral 4-(f-butoxycarbonylamino)pyrazolidin-3-one 272. The Michael addition is run in dichloro-methane followed by addition of f-butyl oxalyl chloride and 2 equiv of Huning s base in the same pot to provide 276 in 58% yield. The allyl ester is deprotected using palladium catalysis to give the corresponding acid 277, which is... 

A chromotrophic acid spot test for formaldehyde (23) was also negative for the polymer ozonolysis solution, while it was positive for a control solution containing formaldehyde equivalent to that expected in the experimental solution if one per cent of the double bonds were vinyl, i.e., polymerization via the internal double bond. 

A spectrophotometric method for aldehydes in either fresh or seawater was described by Kamata [ 132], It used the colour-forming reaction between the aldehyde, 3-methyl-2-benzothiazolone hydrazone, and ferric chloride, and claimed a sensitivity of 0.01 mg/1 as formaldehyde equivalents. While Kamata clearly found evidence of the presence of aldehydes, the method appears to be not quite sensitive enough for the quantities to be found in seawater. 

On the way to the 2-unsubstituted 3-aminoimidazo[l,2-a]heterocycles, Lyon and Kercher [141] suggested interesting approach involving glyoxylic acid as formaldehyde equivalent in the three-component reaction. According to the standard protocol, glyoxylic acid was introduced either in solution or captured on the macroporous... 

Entries 1 and 2 in Scheme 2.11 show the preparation of Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as bis(dimethylamino)methane in entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. 

Di-tert-butyl methylenemalonate was originally prepared by phenyl-sulfenylation of di-tert-butyl methylmalonate and thermal elimination of the related sulfoxide.8 Because methylenemalonate esters are customarily prepared by Knoevenagel-type condensation of malonic esters with formaldehyde equivalents, the considerably more convenient procedure described herein was subsequently adapted from Bachman and Tanner s study using paraformaldehyde under metal ion catalysis.39 The approximately 6% di-tert-butyl malonate accompanying the product has presented no interference in the aforementioned reactions with nucleophilic alkenes under neutral or acidic conditions, but its presence should be taken into consideration in other applications. 

The propargylic alcohol group may be exploited as an allylic alcohol precursor (Eq. 6A.2) and may be generated by nucleophilic addition to an electrophile [25] or by addition of a formaldehyde equivalent to a preexisting terminal acetylene group [26], Once in place, reduction of the propargylic alcohol with lithium aluminum hydride or, preferably, with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) [27] will produce the trans allylic alcohol. Alternately, catalytic reduction over Lindlar catalyst can be used to obtain the cis allylic alcohol [28]. The addition of other lithium acetylides to ketones produces chiral secondary alcohols, which also can be reduced by the preceding methods to the cis or trans allylic alcohols. Additional synthetic approaches to allylic alcohols may be found in the various references cited in this chapter. 

The mechanism of the reaction is considered in Section 6.12.7, p. 1050, where acetophenone, which can only enolise in one direction, reacts with the formaldehyde equivalent (17) formed from formaldehyde and dimethylamine hydrochloride, to give the Mannich base (18), which in this case is isolated as the hydrochloride. The free Mannich bases are obtained by treatment with base and solvent extraction or crystallisation (e.g. gramine, Expt 6.147). 

Other methods which are variously suitable for the formylation of aromatic hydrocarbons, phenols, phenolic ethers and heterocyclic systems, employ a range of alternative formaldehyde equivalents. These latter include the species 0... 

Finally, it should be noted that a specific ortho formylation process which uses 1,3-dithiane as a formaldehyde equivalent has been described.48 The reaction process appears to be of wide applicability and is similar to the ortho formylation of primary aromatic amines which has been described by the same authors (see p. 909). 

We need a formaldehyde equivalent that is less electrophilic than formaldehyde itself and will therefore add only once to enol(ate)s. The solution is the Mannich reaction.7 Formaldehyde is combined with a secondary amine to give an iminium salt that adds 47 to the enol of the aldehyde or ketone in slightly acidic conditions to give the amino ketone (or Mannich base ) 48. If the product of the aldol reaction 50 is wanted, alkylation on nitrogen provides a good leaving group and ElcB elimination does the trick. 

The propargylic alcohol group may be exploited as an allylic alcohol precursor (equation 2) and may be generated by nucleophilic addition to an electrophile or by addition of a formaldehyde equivalent to a preexisting terminal alkyne group. Once in place, reduction of the propargylic alcohol with lithium... 

C((x)-C(p) bond cleavage in a-amino acids is precedented by the PLP-containing enzyme serine hydroxymethyltransferase, interconverting serine with glycine and a formaldehyde equivalent, but in that case C-C bond cleavage is a retro aldol process This route is not obviously open to ACPC (9). 

Iminium salts bearing a labile trimethylsilyl group can be generated in situ and undergo nucleophilic addition (see Sections 1.12.4.2 and 1.12.7.3). Bis(trimethylsilyl)methoxymethylamine (75), for example, has been used as a formaldehyde equivalent for the preparation of primary amines. Cyclic imines, such as 3,4-dihydroquinolines, react with trimethylsilyl triflate (TMS-OTf) to provide reactive labile iminium salts (55), which condense with picoline anions. The addition of nonstabilized Grignard and organolithium reagents to acyclic aromatic ketimines and aldimines, however, is often not facilitated by the presence of TMS-OTf ... 

Theoretically 100 grams of pure methanol should yield 93.75 grams of pure formaldehyde, equivalent to 256.9 grams of 40 per cent formaldehyde solution. In practice about 82 per cent of theory is realized. High yields of over 90 per cent are possible only in laboratory apparatus or for short periods of time in commercial apparatus.18... 

The evidence described above thus indicates that the structure of macralstonine is almost certainly XLIa b, and it is presumably formed in the plant by a Michael reaction between alstophylline and macroline, or alternatively, by a Mannich reaction involving alstophylline, the hydroxyketone XLIII, and a formaldehyde equivalent. The acid fission of macralstonine to alstophylline and macroline or to alstophylline, XLIII, and formaldehyde is thus seen to be the reverse of these reactions (10). 

We need a formaldehyde equivalent which is less reactive than formaldehyde itself. The most popular method is the Mannich reaction " in which formaldehyde reacts with the enolic component and a secondary amine. The mtermediate (41) is first formed this adds to the enol to form the Mannich base (42). 

The evidence for an enzyme-bound formaldehyde equivalent is based mainly on the observations of (1) the utilization of a-methylserine as a substrate (F is about 10% that for serine) and (2) the cleavage of /8-hydroxy-L-amino acids including serine in the absence of H4-folate. Hence a covalent adduct involving H4-folate in order to break the C -C bond [55] is not required. Statement 1 opposes the anticipated addition-elimination of HjO from the seryl-pyridoxal phosphate complex prior to its trapping by H4 folate (9) so as to remove after tautomerization the C-3 unit of serine and form 5,10-CH2-H4-folate. Statement 2 suggests that the role... 

This reaction is less sensitive than that of the pararosaniline method. Other aldehydes undergo an analogous reaction, but the yield is generally lower. The MBTH method quantifies total aldehydes in ambient air in terms of their formaldehyde equivalents. Strong reducing agents can interfere with the determination of aldehydes. 

Tetroses and Pentoses - 4-0- -Butyldimethylsilyl-2,3-0-isopropylidene-L-threose (1) has been prepared in seven efficient steps from o-xylose. 3,4-0-Isopropylidene-D-eythrulose (4) has been synthesized from the known tetritol derivative 2 by primary protection as the silyl ether 3, followed by Dess-Martin oxidation and desilylation. Compound 2 was derived from D-isoascorbic acid (see Vol. 22, p. 178, refs. 9,10). In a similar reaction sequence, the enantiomer 5 has been obtained from L-ascorbic acid. The dehomologation of several di-0-isopropylidenehexofuranoses e.g., 6- 7) has been carried out in two steps without intermediate purification, by successive treatment with periodic acid in ethyl acetate, followed by sodium borohydride in ethanol. Selective reduction of 3-deoxy-D-g/jcero-pentos-2-ulose (8) to 3-deoxy-D-g/> cero-pent-2-ose (9) has been achieved enzymically with aldose reductase and NADPH." 4-Isopropyl-2-oxazolin-5-one (10) is a masked formaldehyde equivalent that is easily converted to an anion and demasked by mild acid hydrolysis. One of the three examples of its use in the synthesis of monosaccharides is shown in Scheme 1. ... 

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