Sodium bisulfite, aldehyde reaction

In a 4-I. wide-mouthed glass jar, fitted with a mechanical stirrer, is placed a solution of 150 g. (3 moles) of sodium cyanide (Note i) in 500 cc. of water and 318 g. (3 moles) of u.s.P. benz-aldehyde. The stirrer is started and 850 cc. of a saturated solution of sodium bisulfite (Note 2) is added to the mixture, slowly at first and then in a thm stream. The time of addition is ten to fifteen minutes. During the addition of the first half of this solution, 900 g. of cracked ice is added to the reaction mixture, a handful at a time. The layer of mandelonitrile which appears during the addition of the sulfite solution is separated from the water in a separatory funnel. The water is extracted once with about 150 cc. of benzene, the benzene is evaporated, and the residual mandelonitrile is added to the main portion. 

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. ... 

Seventeen grams of acetaldehyde are dissolved in 20ml of water and added dropwise to a suspension of 40g of sodium bisulfite in 30ml of water. The reaction mixture is kept cold in an ice bath to prevent loss of the aldehyde by volatilization much heat Is liberated by the formation of the bisulfite addition compound. The temperature of the solution is adjusted to 50°C and 17ml of 20% aqueous ammonia are added. The latter is prepared from 13ml of the... 

Lithium chloride (2.6 g) is dissolved in THF (170 mL). Dimethyl-(2-oxo-4-phenylbutyl)phosphonate (7.87 g) and triethylamine (4.3 mL) are added. The mixture is stirred and cooled to -10°C. A solution of the Corey aldehyde benzoate, (lS,5R,6R,7R)-6-formyl-7-(benzyloxy)-2-oxabicyclo[3.3.0]octan-3-one (8.42 g) in THF (75 mL) is added to the reaction mixture over three hours. The resulting mixture is stirred for 18 hours at -10°C. At the end of this time, methyl t-butyl ether (MTBE) (100 mL) is added and the mixture warmed to 0-20°C. Sodium bisulfite (38%, 100 mL) is added and the two-phase mixture was stirred for 10 min. The phases are separated and the organic phase is washed with saturated aqueous sodium bicarbonate solution (100 mL). The organic phase is separated and concentrated under reduced pressure to a volume of <100 mL. Ethyl acetate (200 mL) is added and the... 

The last nucleophile of this chapter, sodium bisulfite, NaHSC, adds to aldehydes and some ketones to give what is usually known as a bisulfite addition compound. The reaction occurs by nucleophilic attack of a lone pair on the carbonyl group, just like the attack of cyanide. This leaves a positively charged sulfur atom but a simple proton transfer leads to the product. 

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. 

The reversibility of the reaction makes bisulfite compounds useful intermediates in the synthesis of oilier adducts from aldehydes and ketones. For example, one practical method for making cyanohydrins involves bisulfite compounds. The famous practical book Vogel3 suggests reacting acetone first with sodium bisulfite and then with sodium cyanide to give a good yield (70%) of the cyanohydrin. 

The reaction is carried out by mixing the aldehyde or ketone with a concentrated aqueous solution of sodium bisulfite the product separates as a crystalline solid. Ketones containing bulky groups usually fail to react with bisulfite, presumably for steric reasons. 

Bisulfite Addition Products and the Bucherer Reaction. The addition of sodium bisulfite to aldehydes and some ketones superficially appears to involve the addition of the elements Na and HS03 to the carbonyl group. Kinetic studies, however, indicate that the reaction is complicated and probably involves sulfite rather than bisulfite ion.10 One possible mechanism is the following ... 

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. 

Sodium bisulfite adducts are readily formed from aldehydes by reaction with NaHSOs. These derivatives are often crystalline and thus serve as a convenient method for purification of aldehydes. Reversion to the aldehyde usually is accomplished by treatment with aqueous acid or base. TMSCl can be used to regenerate the aldehyde under nonaqueous conditions. ... 

The 2-cyclohexylacetaldehyde is too air sensitive and needs to be protected to be further handled and stored. The aldehyde was protected either as a dimethylacetal or as a sodium bisulfite adduct. However, we discovered that the dimethylacetal derivative was unreactive in the reaction conditions (acidic) in the Pictet-Spengler reaction generating the tetrahydro-p-carboline derivative. In addition, the dimethylacetal derivative is an oil, making its isolation difficult on the plant scale. Therefore, we choose to isolate the 2-cyclohexylacetaldehyde as a bisulfite adduct, yielding a white crystalline solid. 

The acid-catalyzed Pictet-Spengler reaction between tryptamine derivatives and aldehydes is a well-established method for preparing tetrahydro-p-carboline (THpC) derivatives." Our first trials were aimed at using the bisnlfite adduct as the carbonyl sonrce in order to minimize the number of process steps. The reaction was performed by reacting the 5-methyltryptamine hydrochloride with an excess (1.3 eqniv) of the sodium bisulfite adduct in EtOH at reflnx, in the presence of one extra eqnivalent of HCl. The rac-THpC was simply isolated as a hydrochloride salt by filtration of the reaction mixture (Scheme 6.8). 

Pictet-Spengler Reaction Using Sodium Bisulfite Adduct or Free Aldehyde... 

The a-amino nitrile 139, a key intermediate in the synthesis of (+)-biotin, is prepared through a highly diastereoselective Strecker reaction of the bisulfite adduct 138 <04TL6579>. This bisulfite is derived from the a-amino aldehyde 137 upon treatment with sodium bisulfite. 

Sulfomethylation. Sodium hydroxymethanesulfonates ( aldehyde bisulfites ) are used to sulfomethylate on reactive carbon atoms (e.g., in phenols or ketones) or oh nitrogen (i.e., amines, amides, or sulfoamides) by the following reactions ... 

Sodium bisulfite adds to aldehydes (most of them) to form bisulfite addition products. This utility is in separating a carbonyl compound from non-carbonyl compounds, The reaction is illustrated as follows ... 

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