Cyclohexanone Semicarbazon

Problem 15.31 Reaction of 1 mole of semicarbazide with a mixture of 1 mol each of cyclohexanone and benzaldehyde precipitates cyclohexanone semicarbazone, but after a few hours the precipitate is benzaldehyde semicarbazone. Explain. ... 

When a mixture of 0.01 mol of each of cyclohexanone (7), furfural (8) and semicarbazide (Scheme2.4) reacted in aqueous ethanol at25°C, the product isolated after a few seconds was cyclohexanone semicarbazone (9) but, after a few hours, the product was the semicarbazone... 

For example, Conant and Bartlett studied the formation of semicarbazones from a solution composed initially of equal concentrations of cyclohexanone (65), furfural (66), and semicarbazide hydrochloride (67) in a solution of KOAc in 50% aqueous ethanol. The product isolated after a reaction period of 20 seconds was cyclohexanone semicarbazone (68, equation 6.57). However, when the reaction was allowed to proceed for 2.5 hours, the product was furfural semicarbazone (69, equation 6.58). ... 

Place 0.3 g of cyclohexanone semicarbazone. prepared in Part A. 0.3 mL of 2-furaldehyde, 2 ml of 95% ethanol, and 10 mL of water in a 25-mL Erlen-meyer flask. Warm the mixture until a homogeneous solution is obtained (about 1 or 2 min should suffice), and continue warming for an additional 3 min. Cool the mixture to room temperature and then place it in an ice-water bath. Collect the crystals on a filter, and wash them with 2-3 mL of cold water. Thoroughly air-dry the crystals and determine their weight and melting point. 

Repeat the preceding experiment, but use 0.3 g of 2-furaldehyde semicarbazone (prepared in Part B) and 0.3 mL of cyclohexanone in place of the cyclohexanone semicarbazone and 2-furaldehyde. 

Any precipitate formed is claimed to be without influence. Nevertheless, in this way, the wave of cyclohexanone semicarbazone was lowered by about 30 per cent due to the treatment with silver oxide. However, the determination of acetone was uninfluenced even by a twentyfold excess of butyraldehyde. 

Gyclohexanone semicarbazone hydrogenated 3 hrs. with Raney-Ni in ethyl acetate cyclohexyl semicarbazide (Y 95.5%) dissolved in chloroform and treated with 1 mole of 40%-peroxyacetic acid cyclohexylazoformamide (Y 89.7%) dissolved in alcohol and treated with a few drops of NaOH-soln. cyclohexanone semicarbazone (Y ca. 100%). L. Horner and H. Fernekess, B. 94,712 (1961). 

Reactions of ketones (use acetone reactions (i), (ii), (iii) and (vi) as for aldehydes cyclohexanone oxime (J scale), cycibhexanone phenyl-hydrazone, and acetone semicarbazone (J scale) as in 111,74. ... 

Me,SiCl (6.5 g, 60 mmol) in CCl4 (10 ml) is added to the semicarbazone (30 mmol), NaN02, or NaNOj (42 mmol), TEBA-Cl (0.34 g, 1.5 mmol) in CCI4 (20 ml) and the mixture is stirred for 3 h at room temperature. The mixture is filtered through silica and evaporated to yield the carbonyl compound (e.g. EtCOMe, 78% 1-BuCOMe, 84% cyclopentanone, 83% cyclohexanone, 78% PhCHO, 95% PhCOMe, 80% Ph2CO,... 

The C=0 of cyclohexanone is not deactivated by the electron-releasing C H, and does not suffer from steric hinderance. The semicarbazone of cyclohexanone is the kinetically controlled product. Conjugation makes... 

Semicarbazide (1 mole) is added to a mixture of cyclohexanone (1 mole) and benzaldehyde (1 mole). If the product is isolated immediately, it consists almost entirely of the semicarbazone of cyclohexanone if the product is isolated after several hours, it consists almost entirely of the semicarbazone of benzaldehyde. How do you account for these observations ... 

When the product is isolated immediately, most of it consists of the semicarbazone of cyclohexanone, whereas hours later it is mostly the semicarbazone of benzaldehyde. These observations strongly suggest semicarbazide formation is reversible. Cyclohexanone reacts more rapidly, but benzaldehyde gives the more stable product so that it will predominate in time. Initially, one isolates the product of rate control (the compound that reacts with greatest speed). Later, after the equilibrium is established, one isolates the product of equilibrium control (greatest stability). 

The principle of kinetic and thermodynamic control in organic chemistry may be illustrated by studying the competing reactions of semicarbazide (1) with two carbonyl compounds, cyclohexanone (2) and 2-furaldehyde (4), as shown in Equations 13.3 and 13.4, respectively. In this case, one compound, semicarbazide, reacts with two different compounds, cyclohexanone and 2-furaldehyde, to give two different semicarbazones, 3 and 5, respectively. Both products are crystalline solids that have distinctive melting points by which they may be easily identified. Thus, it is easy to determine experimentally which compound is the product of kinetic control and which is the product of thermodynamic control. 

For best results, the 2-furaldehyde should be freshly distilled immediately before use. Prepare the semicarbazone of 2-furaldehyde by following the procedure of Part A exactly, except use 0.4 mL of 2-furaldehyde instead of 0.5 mL of cyclohexanone. Recrystallization of the product is unnecessary. Obtain IR and NMR spectra of your starting material and product. Compare your spectra with those of authentic samples (Figs. 13.7-13.10). 

---