Phenyl-2-propanone Syntheses

Preparation of Phenyl-2-Propanone from Ephedrine or psearfo-Ephedrine 

1025 g 75% sulphuric acid are mixed with 2 gAlClS. Therein 426 g (= 2.58 Mol) ephedrine or pseudoephedrine at 50 to 100°C are added. Subsequently, the mixture on 145 to 150° heated, with 125°C is introduced water vapour in moderate stream for better mixing. At 145°C one increases steam distllation and distills for period of 2-1/2 to 3 hours, the azeotrop phenylacetone/water distills over. 

From the distillate one isolates by toluene extraction a raw phenylacetone, which is free from propiophenone. After distillation over a short Vigreux column one receives 270 g (78%) phenylacetone, purity 99.8%. similar to the one received from norephedrine and/or norpseudoephedrine, phenylacetone in a absolute yield of approx. 80% 

1000 g 79% sulphuric acid and 100 g (-)-pseudoephedrine, whereby the H2S04-concentration is adjusted to 65 to 66%. This solution is given to 2 L three-neck, mixed with 4 g A1C13 and heated up on 125 to 130°C. 

By injecting water vapour one increases the temperature to 145 - 150°C and leaves from now to continuously with a speed of approximately 1 to 5 g/min, 70 to 90° C a warm a solution of (-)-pseudoephedrine into 79% sulphuric acid (weight ratio 1 1) over a steam-heated dropping funnel flow. The phenylacetone turns into thereby as Azeotrop and similar to example 1. 

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For preparative purposes fermenting baker s yeast (Saccharomyces cerevisiae) is commonly used instead of a purified enzyme preparation. However, isolated pyruvate decarboxylates can also be used30. In this context, the most important substrate is benzaldehyde31 which is converted by n-glucosc fermenting yeast to (7 )-l-hydroxy-l-phenyl-2-propanone. This conversion has gained considerable industrial importance because ( )-l-hydroxy-1-phenyl-2-propanonc is an important precursor for the synthesis of (-)-cphedrin. 

Figure 4.2 Enzyme-hi-membrane-reactor synthesis of 1-pheny 1-2-propanol from l-phenyl-2-propanone applying a stirred-tank reactor, ultrafiltration module, extraction module and distillation...

Phenyl-2-propanone Used in the chemical and pharmaceutical industries for the manufacture of amphetamine, methamphetamine and some derivatives used for the synthesis of propylhexedrine. 

There are several ways to accomplish this synthesis. One approach would follow the example described in eq. 11.13. Reaction of 1-phenyl-2-propanone with methylamine would give an imine. Reduction of the imine would afford methamphetamine, which would give methamphetamine hydrochloride upon reaction with HCI. 

Hydroxyketones are versatile intermediates in the synthesis of pharmaceutical intermediates and heterocyclic molecules. a-Aryl hydroxyketones have been prepared by reaction of aryl aldehydes with 1,4-dioxane followed by reduction with lithium aluminum hydride (LAH) and by the selective LAH reduction of a-silyloxy a,P-unsaturated esters." WissneC has shown that treatment of acid chlorides with tris(trimethylsilyloxy)ethylene affords alkyl and aryl hydroxymethyl ketones. 1-Hydroxy-3-phenyl-2-propanone (3) has been generated by the osmium-catalyzed oxidation of phenylpropene and by the palladium-catalyzed rearrangement of phenyl epoxy alcohoP both in 62% yield. 

Thietanones also have been obtained by treatment of aliphatic ketones with an a-methylene group with thionyl chloride, usually in the presence of a base as shown for the synthesis of 359. A 3-thietanone was suggested as a possible structure for the product obtained by the acid-catalyzed hydrolysis of the bis-thioglycolic thioacetal of substituted benzaldehydes, but an elemental analysis was the only evidence. Treatment of l-diazo-3-phenylthio-2-propanone with acid gives the -phenyl salt of 3-thietanone (Section VII.1.). Similar 5-alkyl salts may be intermediates, but they readily decompose either by loss of the 5-alkyl group or... 

Probkm 28.28 Using 9-BBN plus any alkenes and unhalogenated acids or ketones, outline all steps in the synthesis of (a) 2-heptanone (b) 4-methylpentanoic acid (c) 4-methyl-2-hexanone (d) l-cyclohexyl-2-propanone (e) ethyl (trans Z-methylcyclopentyl)acetate (f) l>phenyl-4-methyM-pentanone (g) i-cyclopentyl-33 dimethyl-2-butaBone. 

Experiments were first conducted with acetic and polyphosphoric acids, and with several concentrations of H2SO4. As expected for a methyl ketone, with 1-phenyl-2-propanone phenylhydrazone use of PPA catalyst resulted in a large variation in isomer ratio (see Table 1). With 3-heptanone the variations resulting from use of different acids were much smaller. Of several active zeolite catalysts tested, H-beta was found to be the most selective heterogeneous catalyst for the synthesis of the linear isomer from 3-heptanone and l-phenyl-2-butanone phenylhydrazones whereas, in contrast, H-Na-Y gave about equal amounts of both isomers. 

Appreciable formation of the linear 2-benzyl-3-/f-indole by the Fischer synthesis with 1-phenyl-2-propanone was only observed with polyphosphoric acid and not at all with zeolite beta, although this product resembles, in bulkiness, 2-benzyl-3-methylindole, the linear indole isomer obtained from 1-phenyl-2-buta-none. If the production of the linear isomer depended solely on suppression of the formation of the bulky product, then the trends in the selectivities for 1-phenyl-... 

Aryl-2,3-epoxy-l-phenyl-l-propanone (44) was revealed as a key intermediate for the synthesis of 1,3,5-triarylpyrazoles (45) in 69%-99% yields via a reaction with phenylhydrazine (23) catalyzed by HCl under ultrasonic irradiation at room temperature (Scheme 8.15). The same reactions performed in the absence of sonication gave substantially poorer yields (Li et al. 2010a). 

Li et al. [57] have found an efficient and practical procedure for the synthesis of 5-aryl-l,3-diphenylpyrazole (34) via the condensation of 3-aryl-2,3-epoxy-l-phenyl-l-propanone (32) and phenylhydrazine (33) xmder ultrasoxmd... 

Devise a synthesis of Apetinil, an appetite suppressant, firom each of the following starting materials, (a) l-phenyl-2-bromopropane (b) l-phenyl-2-propanone... 

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