Bisulfite addition compound

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. 

What is happening here The bisulfite compound forms first, but only as an intermediate on the route to the cyanohydrin. When the cyanide is added, reversing the formation of the bisulfite compound provides the single proton necessary to to give back the hydroxyl group at the end of the reaction. No dangerous HCN is released (always a hazard when cyanide ions and acid are present together). 

Cyanohydrins can be converted by simple reactions into hydroxyacids or amino alcohols. Here is one example of each, but you will have to wait until Chapter 12 for the details and the mechanisms of the reactions. Mote that one cyanohydrin was made by the simplest method—just NaCN and acid—while the other came from the bisulfite route we have just discussed. 

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 

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The soiution is aliowed to cool and the crystals of the P2P-bisulfite addition compound are then separated by vacuum filtration, washed with a little clean dH20 then washed with a couple hundred mLs of ether, DCM or benzene. The filter cake of MD-P2P-bisulfate is processed by scraping the crystals into a flask and then 300mL of either 20% sodium carbonate solution or 10% HCi soiution are added (HCI works best). The soiution is stirred for another 30 minutes during which time the MD-P2P-bisulfite complex will be busted up and the P2P will return to its happy oil form. The P2P is then taken up with ether, dried and removed of the solvent to give pure MD-P2P. Whaddya think of that ... 

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. 

Nature Identical Flavor Matenal A flavor ingredient obtained by synthesis, or isolated from natural products through chemical processes, chemically identical to the substance present in a natural product and intended for human consumption either processed or not eg, citral obtained by chemical synthesis or from oil of lemongrass through a bisulfite addition compound. 

SuWta.tlon. Sulfur dioxide is added to a level of about 150 ppm on juice to discourage further color-forming Malliard reactions by tying up the small amount of invert sugars as bisulfite addition compounds. 

Sodium bisulfite adds to the carbonyl double bond to give a hydroxysulfonate (bisulfite addition compound). 

Ketones are more stable to oxidation than aldehydes and can be purified from oxidisable impurities by refluxing with potassium permanganate until the colour persists, followed by shaking with sodium carbonate (to remove acidic impurities) and distilling. Traces of water can be removed with type 4A Linde molecular sieves. Ketones which are solids can be purified by crystallisation from alcohol, toluene, or petroleum ether, and are usually sufficiently volatile for sublimation in vacuum. Ketones can be further purified via their bisulfite, semicarbazone or oxime derivatives (vide supra). The bisulfite addition compounds are formed only by aldehydes and methyl ketones but they are readily hydrolysed in dilute acid or alkali. 

Impurities resulting from storage can be removed by passage through chromatographic grade alumina. Furfural can be separated from impurities other than carbonyl compounds by the bisulfite addition compound. The aldehyde is steam volatile. 

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. 

Bisulfite Addition Compounds (see Hydroxy Sulfonic Acids)... 

The crude aldehyde (prior to distillation) is sufficiently pure for most purposes. Isolation of the aldehyde may also be achieved by means of the bisulfite-addition compound.2... 

The melting point of 1-naphthaldehyde given by Stephen (33-34°) is apparently incorrect. A sample that was purified through the bisulfite addition compound and redistilled had a freezing point of 2.5°. 

The postulated 1-aminoalkylarsonic acids have something in common with 1-hydroxyalkanesulfonic acids, R—CHOH—S03-. These are not usually known as such, but as bisulfite addition compounds of aldehydes. They are not usually isolable, because of the ease of the reaction shown in Fig. 14. In just the same way we might expect R— CH(—NH3+)—As03H to lose arsenite as H2As03" and H+, i.e., H2As03" overall, leaving the imine R—CH=NH2+, which would equilibrate with R—CH=0 and NH4+. So this would explain why 1-amino-alkylarsonic acids may not exist as stable compounds. 

The sodium bisulfite addition compounds must have a free (or potentially free) ketone-type carbonyl group, since they readily form derivatives with typical ketone reagents such as semicarbazide and 2,4-dinitrophenylhydrazine.174 Decomposition of these derivatives with alkali gives the corresponding adrenochrome derivatives e.g., adrenochrome monosemicarbazone would be obtained from the semicarbazone of the adrenochrome-sodium bisulfite complex.174 If one accepts Tse and Oesterling s formulation of the adrenochrome-sodium bisulfite complex, the semicarbazone would probably have a basically similar structure (i.e. 82). This type of structure is more... 

Cytidine reacts in the same way, but the bisulfite addition compound is unstable. These C5-C6 adducts of cytidine all have a greatly enhanced reactivity at C4,... 

The sodium bisulfite purification step may be omitted, and the alkylidene ester purified directly by distillation. Care must be taken to separate the product from ethyl cyanoacetate by fractionation through a moderately efficient column. Purification through the bisulfite addition compound is recommended for alkylidene cyanoacetic esters derived from ketones containing four and five carbon atoms, but not for the higher homologs. 

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... 

Cyanohydrins can be formed by the acid- or base-catalyzed reaction of hydrogen cyanide with an aldehyde or ketone, the displacement of bisulfite ion by cyanide ion on the bisulfite addition compounds of aldehydes and... 

Compensation has recently been observed in the dissociation of bisulfite addition compounds (Blackadder and Hinshelwood, 1958), in the ionization of phenols (Chen and Laidler, 1962), in the alkaline hydrolysis of certain cyclopentyl acetates (Bruice and Fife, 1962), and in the acylation of aromatic amines (Venkataraman and Hinshelwood, 1960). 

Aldoses behave like aldehydes, but react much more slowly. The bisulfite addition compound is much more unstable. When, say, acetaldehyde is added to a glucose-bisulfite solution, the bisulfite will be transferred to it. 

Ketoses do not form bisulfite addition compounds. This fact shows also that formation of the bisulfite compound of the sugar is not essential, since S02 prevents browning by ketoses also. 

Aldose-bisulfite addition compounds are the least stable and decompose even in aqueous solution on heating. 

The self-condensation of the bisulfite addition compound of an a-oximinoketone followed by reaction with potassium cyanide and hydrochloric acid yields 3,6-dicyano-2,5-dialkylpyrazines or, in the case of oximinoacetophenone, a mixture of 3-cyano-2,5-diphenyl-pyrazine and 3,6-dicyano-2,5-diphenylpyrazines.227... 

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. 

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