Formaldehyde equivalent reaction

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. 

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... 

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 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). 

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 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). 

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. ... 

Over time, the reaction has become a rather important synthetic method in organic chemistry, as the chloromethyl group can be easily converted into a variety of functional groups. A number of different procedures have been used to effect this transformation. In addition to formaldehyde, several formaldehyde equivalents have been used, including... 

Most recently, ElSohly and coworkers [23] have reported the isolation of a A -THC dimer, called cannabisol (17) from high-potency marijuana samples. Authors h3 pothe-sized that the methylene bridge connecting the two THC units could derive from a Claisen-type reaction between two THCA units followed by decarboxylation and enzymatic reduction of the resulting ketone. A dicumarol-type biogenesis involving the reaction of two molecules of THC with one formaldehyde-equivalent seems also plausible. Unfortunately, the impact on the activity of this dimerization has not been reported. 

For the use of carbohydrates catalytically activated as acyl anions to act as formaldehyde equivalents, see the section titled Stetter Reaction below. 

Metal carbene centers may be coimected via either the carbon or the heteroatom carbene chain [47]. The first example of a homodimetallic biscarbene complex has been synthesized by trapping a metal carbene anion - generated in situ by a-de-protonation of chromium oxacyclopentylidene 73 - by its exo-methylene congener 74 formed upon the addition of the same chromium carbene anion to formaldehyde in a Michael-type addition reaction [48]. A more satisfactory yield of bischro-mium biscarbene 75 has been obtained by using the formaldehyde equivalent CICH2OCH3 as source of the Cj-bridge and Lil (Scheme 11.23). 

In alkaline solution formaldehyde can be electrolytically oxidized to formic acid and carbon dioxide. When a specially prepared copper or silver anode is employed, Muller reports that pure hydrogen is liberated in equal amounts from both cathode and anode. Under these circumstances sodium formate is produced in theoretical quantity and two equiva lents of hydrogen are liberated for each faraday of electricity. The anode is best prepared by treating copper or silver with molten cuprous or silver chbride respectively and then subjecting to cathodic reduction in a solution of sodiu m hydroxide. Approximately equivalent results were obtained vith 0.6 to 2N alkali containing about 17 per cent dissolved formaldehyde. The reactions taking place are shown below as postulated by Muller. 

The condensation reaction of resorcinol with formaldehyde, on an equal molar basis and under identical conditions, also proceeds at a rate which is approximately 10 to 15 times faster than that of the equivalent phenol-formaldehyde system [16-18,123]. The high reactivity of the resorcinol-formaldehyde system renders it impossible to have these adhesives in resol form. Therefore, only resorcinol-formaldehyde novolaks, i.e. resins not containing methylol groups can be produced. All the resorcinol nuclei are linked together through methylene... 

In theory, periodate oxidation could have given a clear-cut answer as to the composition of the isomeric mixture of deoxy ribose phosphates. The 4-phosphate (73), devoid of vicinal diol groups, should be resistant to periodate the 3-phosphate (74) should reduce one and only one molar equivalent of the oxidant and yield one molar equivalent of both formaldehyde and the phosphorylated dialdehyde (75), whereas the 5-phosphate (76) could be expected to reduce one molar equivalent of periodate relatively rapidly, followed by a slower overoxidation reaction owing to the oxidation of malonaldehyde, formed as a result of the glycol cleavage. 

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