Reaction with bisulfite addition products

Not-Strike may have seen. But what Dr. Quack did that SWINS did not was use the bisulfite test with positive results. What does that mean It means that some doublebonded oxygen was formed, unless Dr. Quack was fibbing to us, It cannot have been a propiophenone (don t ask) because propiophenones cannot form the bisulfite addition product. Could an aldehyde have formed (don t ask) Maybe. But highly unlikely considering the mechanism of the reaction. 

Bisulfite addition products are formed from aldehydes, methyl ketones, cyclic ketones (generally seven-membered and smaller rings), a-keto esters, and isocyanates, upon treatment with sodium bisulfite. Most other ketones do not undergo the reaction, probably for steric reasons. The reaction is reversible (by treatment of the addition product with either acid or base ) and is useful for the purification of the starting compounds, since the addition products are soluble in water and many of the impurities are not. ... 

Frequently, it is the bisulfite addition product that is treated with CN. This method is especially useful for aromatic aldehydes, since it avoids competition from the benzoin condensation. If desired, it is possible to hydrolyze the cyanohydrin in situ to the corresponding a-hydroxy acid. This reaction is important in the Kiliani-Fischer method of extending the carbon chain of a sugar. 

F. Sodium Bisulfite Addition Product Formation The red color of aminochrome solutions is rapidly discharged by the addition of sodium bisulfite with the formation of pale-yellow fluorescent solutions. The reactions of adrenochrome with sulfites and bisulfites have been the subject of several previous reports.12, 102.109.118,119.123,128,148.182.155. 158,173-177 Although it was originally... 

From the reaction of aminoguanidine with 2-bromoisobutyraldehyde dimethylacetal (522) a product was isolated which was assigned structure (523) or a tautomer thereof (70BSF1606). Semicarbazide (459a) reacts with the glyoxal-bisulfite addition product (524) to give a product formulated as structure (525) (28JA2731). 

A mixture of bisulfite addition product (1 mmol) and montmorillonite KSF (300 mg) was taken in a 25-mL Erlenmeyer flask and kept over an alumina bath (heat sink) inside a domestic microwave oven and irradiated for 520 s and the reaction was monitored by TLC. The product was extracted with ethyl acetate (2x 5 mL), washed with brine and dried over anhydrous sodium sulfate. Evaporation of the solvent afforded the products in excellent yield. All the products were characterized by 1H NMR spectroscopy and by comparison with IR spectra of authentic samples. 

Benzal chlorides. Benzaldehyde or the bisulfite addition product reacts with thionyl chloride and DMF at -10 20° to form benzal chloride, QHsCHCU, in 88% yield. Newman favors structure 1 for the Vilsmeier complex involved in this reaction. This reaction is general for aromatic aldehydes and a, -unsaturated aldehydes. The reaction is not observed with diaryl ketones. 

Like other carbonyl addition reactions, this one is reversible. Addition of acid or base destroys the bisulfite ion in equilibrium with the addition product, and regenerates the carbonyl compound. 

From a theoretical point of view this is an extremely interesting reaction. The displacement of a hydroxyl group from a saturated carbon atom appears to be unknown in basic solution. The fact that amino-methane sulfonic acid can be isolated from the bisulfite addition product of formaldehyde on treatment with ammonia does not prove, of course, that a direct displacement, such as is indicated in XVI to XVII, actually occurred. Furthermore, it is quite clear that preliminary formation of an imine (XVIII) is not necessary for the reaction of aromatic amines with sodium bisulfite (steps XIX to XVIII to XVII, etc.). 1-Dimethyl-aminonaphthalene-4-sulfonic acid (XX) and l-aminonaphthalene-4-sulfonic acid (XIX) show similar reaction kinetics 16a when treated with sodium bisulfite, yet with the tertiary amine (XX) it is not possible to write an imino structure corresponding to XVIII. 

Henry reaction. Formation of nitroalcohols by an aldol-type condensation of nitroparaffins with aldehydes in the presence of base (Henry) or by the condensation of sodium salts of aci nitroparaffi ns with the sodium bisulfite addition products of aldehydes in the presence of a trace of alkali or weak acid (Kamlet). Widely used in sugar chemistry. 

In the preparation of a-keto acids from 2-phenyloxazolones, benzoic acid must be separated from the product. This separation has been effected by saturating the reaction mixture with sulfur dioxide, which forms a bisulfite addition product with the keto acid. Benzoic acid is then removed by filtration or extraction, and the keto acid is subsequently regenerated. These operations are avoided by the use of 2-methyloxazolones, with the added advantage that the 2-methyl... 

The carbohydrates failed to undergo certain reactions that were typical of aldehydes. Although the hexoses and pentoses were readily oxidized at C-1 under mild alkaline conditions, they did not give a positive result with the Schiff test (reaction with basic fuchsin), and they did not form bisulfite addition products, reactions that are typical of aldehydes. The cyanohydrin and phenylhydrazine reactions also went much more slowly than they did for other a-hydroxy aldehydes. 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

Cyclohexanone shows most of the typical reactions of aUphatic ketones. It reacts with hydroxjiamine, phenyUiydrazine, semicarbazide, Grignard reagents, hydrogen cyanide, sodium bisulfite, etc, to form the usual addition products, and it undergoes the various condensation reactions that are typical of ketones having cx-methylene groups. Reduction converts cyclohexanone to cyclohexanol or cyclohexane, and oxidation with nitric acid converts cyclohexanone almost quantitatively to adipic acid. 

Both 1- and 2-naphthylhydrazine have been shown to react in good yield with 2-hydroxy-3-naphthoic acid in the presence of sodium bisulfite to give, after acidic workup, dibenzocarbazole 30 and 31, respectively7 When either 1- or 2-naphthylhydrazine is heated with sodium bisulfite, dibenzocarbazoles 32 and 31, respectively, are isolated after acidic work-up7 It is suggested that loss of the hydrazine residue to form a bisulfite addition compound of the parent naphthol occurs initially further reaction of this adduct with naphthylhydrazine then affords, after work-up, the products. 

Assay procedures for dopamine which are superficially similar to the lutin procedure described above have been reported recently.266-268 The chemistry of the production of the fluorophore from dopamine is, however, somewhat different since the fluorophore is not a 5,6-dihydroxyindoxyl, it is incorrect to refer to the trihy-droxyindole fluorophore of dopamine (cf. ref. 252). Oxidation of the extracted catecholamine is usually carried out with iodine,266-268 presumably with the formation of 7-iodonorepinochrome. The aminochrome is subsequently rearranged to 5,6-dihydroxyindole (it is probable that deiodination accompanies the rearrangement in this case) by a solution of sodium sulfite in aqueous alkali the solution is acidified before measuring the fluorescence of the product (which is said to form relatively slowly and to be very stable).266-268 Irradiation of the reaction mixture with ultraviolet light accelerates the maximal development of fluorescence.266 Since acidification will produce sodium bisulfite in the reaction mixture, it is probable that the fluorophore is a 5,6-dihydroxyindole-sodium bisulfite addition complex. Complexes of this type are known to be both fluorescent and relatively stable in dilute acid solution.118 123,156 265 They also form relatively slowly.255... 

Addition of a nucleophile to the C-6 position of cytosine often results in fascile displacement reactions occurring at the N4 location. With hydroxylamine attack, nucleophilic displacement causes the formation of an N4-hydroxy derivative. A particularly important reaction for bioconjugate chemistry, however, is that of nucleophilic bisulfite addition to the C-6 position. Sulfonation of cytosine can lead to two distinct reaction products. At acid pH wherein the N-3 nitrogen is protonated, bisulfite reaction results in the 6-sulfonate product followed by spontaneous hydrolysis. Raising the pH to alkaline conditions causes effective formation of uracil. If bisulfite addition is done in the presence of a nucleophile, such as a primary amine or hydrazide compound, then transamination at the N4 position can take place instead of hydrolysis (Fig. 38). This is an important mechanism for adding spacer arm functionalities and other small molecules to cytosine-containing oligonucleotides (see Chapter 17, Section 2.1). 

Possible toxic reactions of sulfur dioxide are also indicated in Table I. The reaction of bisulfite with aldehydes has a classic position in biochemistry since Neuberg demonstrated in 1918 that the products of fermentation by yeast were altered by the addition of sodium sulfite, which caused the production of equal amounts of the bisulfite addition compound of acetaldehyde and of glycerol. This was concomitant with the blockage of conversion of acetaldehyde to ethanol. Addition compounds can also be formed with quinones and with ,/ -unsaturated compounds. None of these reactions has been adequately assessed as a possible contributor to toxicity. 

The products are useful for two reasons. They are usually crystalline and so can be used to purify liquid aldehydes by recrystallization. This is of value only because this reaction, like several you have met in this chapter, is reversible. The bisulfite compounds are made by mixing the aldehyde or ketone with saturated aqueous sodium bisulfite in an ice bath, shaking, and crystallizing. After purification the bisulfite addition compound can be hydrolysed back to the aldehyde in dilute aqueous acid or base. 

Naphthols as well as naphthylamines are converted to labile intermediate compounds by the action of bisulfite. These intermediates were considered to be sulfurous acid esters of naphthols (Formula I) by Bucherer, the discoverer of the reaction, but Woroshtzow formulated them as addition products of bisulfite with the keto forms of the naphthols (Formula II). These intermediates yield the corresponding naphthylamines with ammonia, and are hydrolyzed to the naphthols by caustic allrali. Thus, it is possible to convert naphthok into naphthylamines (pages 200 and 203), as well as naphthylamines into naphthols. ... 

O.IN HCl, and 5mCi Na I were combined in a sealed vial, reacted at ambient temperature 20 minutes, and the reaction terminated by addition of 0.1 ml sodium bisulfite (300 mg/ml). The mixture was neutralized with NaHC03, extracted 3 times with 1ml EtOAc, and dried. The product was purified using HPLC on a reverse phase column (PRP-1, Hamilton) eluting with an isocratic solvent consisting of 90% acetonitrile-10% buffer (5 mmol 3,3 -dimethylglutaric acid, pH 7.0) at a flow rate of 1 ml/minute and the product isolated in 50% yield, purity >98%). The radiolabeled compound was stable at room temperature for up to 15 hours. 

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