Ketones with sodium bisulfite

The enhanced reactivity of fluoroalkyl ketones is also manifested in the failure to stop the reaction with hydrogen cyanide at the stage of cyanohydrins Instead, oxazohdinones or dioxolanones are formed (equation 11) If, however, the reaction IS conducted under basic conditions with sodium bisulfite and sodium cyanide, the desired cyanohydrin can be prepared [ll ... 

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. ... 

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 addition of two hydroxylic groups to the double bonds of unsaturated ketones is carried out by the same methods used for hydroxylations of alkenes (equations 71-83). As an example, hydroxylation of the double bond in 3p-hydroxyandrost-5-en-17-one is accomplished by treatment with one equivalent of osmium tetroxide in pyridine and subsequent reductive cleavage of the osmate ester with sodium bisulfite in aqueous pyridine (equation 442) [950. ... 

A number of addition derivatives may be used in the identification of the carbonyl compounds. Of these the crystalline derivatives formed with phenylhydrazine, C6H6NHNH2, and hydroxylamine, NH2OH, are the most important. The products formed with phenylhydrazine are called phenyUiydrazones, and have the general formula, RRiC=NNHC jls. The products formed with hydroxylamine are called oximes, and have the general formula, RRiC=NOH. Other crystalline addition compounds are formed with sodium bisulfite by aldehydes, and by those ketones which contain a methyl group. The addition compounds with ammonia, except in the case of acetaldehyde and a few other carbonyl compounds, are complex products. 

Aldehydes and certain ketones form crystalline addition compounds with sodium bisulfite which are poorly soluble in excess saturated solutions of sodium hydrogen sulfite. If these addition compounds are boiled with acids or alkalies, one can regenerate the corresponding carbonyl compound. 

To 300 ml of a rapidly stirred sodium hypobromite solution (0.512 mole) at 22°C is added 20.1 gm (0.15 mole) of propiophenone over a 5-min period. Stirring is rapid so that the solution exists as an emulsion throughout the reaction. Best yields are obtained under these conditions. Stirring is continued for 2 hr and the mixture kept at 24°-25°C by immersing the flask in an ice bath when necessary. The unreacted hypobromite is destroyed with sodium bisulfite and the basic solution is extracted with ether to remove the unreacted ketone. Acidification of the aqueous phase with concentrated hydrochloric acid yields 17.6 gm (96%) of benzoic acid, mp 121.5°-122°C alone and when mixed with an authentic sample. 

For years chemists have been using sodium bisulfite (that is BISULFITE not BISULFATE) to actually crystallize a ketone out of solution in order to separate it. As it so happens, our happy little MD-P2P is a ketone. And when an oil mixture containing it is mixed with a saturated solution of sodium bisulfite (NaHSOs) the MD-P2P crystallizes out as a bisulfite addition product . It can then be easily separated by filtration. Here s how it goes... 

Anyway, one has the P2P/crap oil, right Right. Next one makes a saturated sodium bisulfite solution by dissolving as much sodium bisulfite as will dissolve in a given amount of water (say, lOOOmL). Now one adds the MD-P2P oil into some of the saturated solution and stirs for 30 minutes. The temperature of the reaction will rise and a big old mass of P2P crystals will form. People often say that the crystals look like chicken fat. Those crystals formed because the bisulfite from the sodium bisulfite latched onto the ketone of the P2P to form a precipitate. And since the P2P is probably the only oil component with a ketone, it is gonna be the only thing of any consequence that crystallizes. 

So now we have this solvent containing ketone, dried with MgS04... Not being able to vac-distill today, took about 50 mis of solvent/ketone and placed in beaker on stir plate and boiled off the solvent. The resulting oil was a nice reddish-orange color. Had a very unique smell too. Took about 2 grams worth of this ail, added to a test tube containing a saturated solution of sodium bisulfite... In less than 60 seconds the oil precipitated into a whitish yellow mass (very similar to what acetone would do if added to a bisulfite solution). Never had this quick of a crystallization. Not... 

The butanals form the conventional aldehyde hydra2one, semicarba2one, and dimedone-type derivatives. In the absence of other aldehydes and ketones, -butyraldehyde can be deterrnined by addition of sodium bisulfite and the excess bisulfite deterrnined with iodine or thiosulfate (34). 

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. 

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. 

In a 3-I. flask are placed a solution of 184 g. (4.6 moles) of sodium hydroxide in 300-400 cc. of water and sufficient ice to make the total volume about 1500 cc. Chlorine is passed into the solution, keeping the temperature below 0° by means of a salt-ice bath, until the solution is neutral to litmus (Note i). After the addition of a solution of 34 g. of sodium hydroxide in 50 cc. of water, the flask is supported by a clamp and equipped with a thermometer and an efficient stirrer. The solution is warmed to 55°, and 85 g. (0.5 mole) of methyl d-naphthyl ketone (Note 2) is added. The mixture is vigorously stirred and, after the exothermic reaction commences, the temperature is kept at 60-70° (Note 3) by frequent cooling in an ice bath until the temperature no longer tends to rise. This requires thirty to forty minutes. The solution is stirred for thirty minutes longer and then the excess hypochlorite is destroyed by adding a solution of 50 g. of sodium bisulfite in 200 cc. of water (Note 4). After cooling to room temperature, the reaction mixture is transferred to a 4-I. beaker and carefully acidified with 200 cc. 

The cyanohydrin of methyl perfluoroheptyl ketone was synthesized by a two-step process addition of sodium bisulfite and subsequent treatment with sodium cyanide. When the ketone was reacted with sodium cyanide, cyclic addition products were obtained, instead of the product of cyanohydrin formation. This result was attributed to the solubility characteristic of a long perfluoroalkyl group, which makes the compound less soluble in water and polar organic solvents [54] (equation 40) (Table 14). 

A solution of 100 g of sodium bisulfite in 200 ml of water is added, and the stirring is continued for 10 hours with exclusion of air. A thick precipitate separates after a few minutes. The bisulfite compound is collected by suction filtration, washed with ether until colorless, and then decomposed in a flask with a lukewarm solution of 125 g of sodium carbonate in 150 ml of water. The ketone layer is separated, and the aqueous layer is extracted four times with 30-ml portions of ether. The combined organic layers are dried over anhydrous magnesium sulfate, the ether is removed at atmospheric pressure, and the residual oil is fractionated under reduced pressure through a short column. The cycloheptanone, bp 64-65°/ 2 mm, is obtained in about 40% yield. 

B. 2-Iodoethyl benzoate. A mixture of 170 g. of anhydrous sodium iodide and 1.2 1. of methyl ethyl ketone (Note 2) is heated on a steam bath for 1 hour with occasional shaking in a 3-1. round-bottomed flask fitted with a water-cooled reflux condenser. 2-Chloroethyl benzoate (162 g., 0.88 mole) is added to the mixture, and heating is maintained for an additional 22-24 hours with occasional shaking. The mixture is cooled to room temperature and filtered through a 15-cm. Buchner funnel with suction. The inorganic salts on the filter are washed with 200 ml. of methyl ethyl ketone, and the filtrate is concentrated by distillation of about 1 1. of the solvent. The residue is poured into 1 1. of water contained in a separatory funnel, which is shaken, and the lower layer is withdrawn. The latter is washed successively with 200 ml. of 10% sodium bisulfite solution, 200 ml. of 5% sodium bicarbonate solution, and 100 ml. of water. It is dried with anhydrous magnesium sulfate (5-7 g.) and fractionated under reduced pressure. The yield of material boiling at 133 -136°/2.5 mm., 1.5820, is 190 -196 g. (78-81%). 

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... 

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. 

Further purification of the product may be effected by converting the ketone into the bisulfite compound, washing this with ether, decomposing with sodium bicarbonate, and steamdistilling. 

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