3- -1 -phenylpropan-1 -one

Isomerization of 2-Benzyl-2-fluorooxirane (10a) to l-Fluoro-3-phenylpropan-2-one (11a) Typical Procedure 47... 

A slightly more complex case was investigated at about the same time by Woolsey and Khalil (1972), namely the reaction of l-diazo-3-phenylpropan-2-one with benzaldehyde (9-9). It is more complex because one might expect a reaction of the aldehyde with the CH2 group of the diazo ketone, and secondly, the reaction was run in ethanol with NaOH as base and not in the system used originally by Schollkopf and his coworkers. The product was, however, 2-diazo-l-hydroxy-l,4-di-phenylbutan-3-one, as expected for an aldol-type substitution. 

Historically, the biocatalytic acyloin condensation was first observed by Liebig in 1913 during studies on baker s yeast [1460]. A few years later, Neuberg and Hirsch reported the formation of 3-hydroxy-3-phenylpropan-2-one (phenyl acetyl carbinol, PAC) from benzaldehyde by fermenting baker s yeast [1461]. Without knowledge on the actual enzyme(s) involved, this biotransformation assumed early industrial importance when it was shown that the acyloin thus obtained could be converted into (-)-ephedrine by diastereoselective reductive amination, a process which is still utilized in almost unchanged form at a capacity of 120 t/year [1462, 1463] (Scheme 2.199). Subsequent studies revealed that this yeast-based protocol can be extended to a broad range of aldehydes [1464, 1465]. 

A suspension of the mercuric acetate complex of l-phenylprop-2-yn-l-ol acetate (prepared with HgO or mercuric acetate) in chloroform stirred and treated with chlorine until refluxing ceases after ca. 4 hrs. for 0.5 mole of complex 1,14-trichloro-3-acetoxy-3-phenylpropan-2-one. Y 50%. F. e. s. R. E. Bowman, A. G. White, and W. R. N. Williamson, Soc. 196A, 1086. 

As a model system, experiments were carried out using (3S)-l,3-dihydroxypentan-2-one 14, which arises from the reaction of propanal with Li-HPA in the presence of E. coli TK. Addition of excess tetrazohum red and sodium hydroxide solution led to a development of a red color within 2 min because of the formation of formazane concomitantly with the diketone. The intensity displayed increased with rising concentrations of 14. According to measurements carried out at 485 nm 14 was detectable down to a corresponding bioconversion of 2.5 mM. As an alternative product from carbohgation to benzaldehyde, l,3-dihydroxy-3-phenylpropan-2-one 15 was also tested in the assay, and comparable levels of detection were determined. 

Aliphatic c a -dibromo ketones, such as 2,4-dibromopentan-3-one (262), react with primary amines RNH2 (R = Me, Et, Pr, /-Pr or t-Bu) to give mixtures of imines 263 and lesser amounts of diimines 264. l,3-Dibromo-l-phenylpropan-2-one yields only the amide 265, the product of a Favorskii rearrangement. The nature of the products from aliphatic amines and cyclic a,a -dibromo ketones depends on ring size the cyclohexanone derivative 266 gave Favorskii amides 267 (R = Pr, /-Pr or t-Bu), while trans-2,5-dibromocyclopentanone afforded the enamines 268 (R = /-Pr or t-Bu) (equation 95)296. 

If , if , 4 )- (lf , 3S, 4 )-4-Acetoxy-3-3-hydroxy-2-oxocyclochexyl acetate (1,2,4)-4-Acetyl-1 -methylcyclohexane-1,2-diol 3-Azido-2-hydroxy-l-phenylpropan-l-one -t3-Azido-2-hydroxy-l-phenylpropan-2-one... 

Oxo-5a-pregnane-3p, 17 a,21 -triol-3,21-acetate 3-Phenyloxy-2-hydroxy-l-phenylpropan-l-one -l-l-Hydroxy-3-phenoxy-l-phenylpropan-2-one Pinacol... 

No loss of optical purity was observed in the mild acidic hydrolysis of the enantiomerically pure 6-alkoxy -phenyl-5,6-dihydro-4/7-l,3-oxazine 132, which resulted in formation of (R)-3-benzoylamino-3-phenylpropanal 133 in excellent yield (Scheme 20). Hydrolysis of the analogous tetrahydro-l,3-oxazin-2-one 134 to 133 required a stronger acidic medium and took place only in poor yield, but without any decrease in the optical purity <20000L585, 2003JOC4338, 2004TL9589>. 

In a detailed study of the reaction of methylene ketones with carboxylic acids in the presence of polyphosphoric acid, pyran-4-ones were obtained from l,3-diphenylpropan-2-one, phenylpropan-2-one and pentan-3-one (61JA193). In the first case, formation of 2,6-dimethylpyran-4-one ( 14 R = H) rather than the 2-benzyl-6-methyl-3-phenyI isomer... 

A suspension of 2,3-dibromo-l-(4-nitrophenyl)-3-phenylpropan-l-one 1 (5 g, 12.2 mmol) in 50 ml of 95% ethanol and 12-15 ml of concentrated ammonium hydroxide was stirred for 6.5 h and filtered (Scheme A.3). nms-2-Phenyl-3-(4-nitrobenzoyl)aziridine 2 was recrystallized from ethanol. Melting point 122-122.5°C. 

Asinger s studies demonstrated that product formation is sensitive to the ratio of sulfur to ketone (1), the structure of the ketone, the replacement of ammonia by amines, the temperature and the medium. Room temperature (20-25 °C) reactions in which the ratio of sulfur to ketones is 0.5 favors the formation of 3-thiazoline, 2, as shown in Figure 1. The formation of 5-alkylidene-3-thiazolines, 3, sometimes competes with the formation of 3-thiazolines such is the case when aryl ketones such as l-phenylpropan-2-one and l-phenylbutan-2-one are employed (4). Also the additional presence of hydrogen sulfide promotes the generation of 1,2,4-trithiolanes and 1,2,4,5-tetrathiolanes from ketones ana aldehydes at the expense of 3-thiazoline formation (11-12). Increasing the S/ketone ratio to 8 favors the formation of the 3-imidazoline-5-thione (5), a product which has a greater tendency to result from aryl methyl ketones (3). 

Irradiation of l,3-bisdiazocyclohexan-2-ones in hydroxylic solvents affords cyclopentene-1-carboxylic acids and esters regiochemical control is only moderate. Although the course of the reactions could be accommodated by sequential Wolff rearrangement and [1,2] H-shift, studies on l,3-bisdiazo-l,3-di-phenylpropan-2-one indicate the formation of the cyclopropenone intermediate (106). ... 

Propafenone, l- 2-[2-hydroxy-3-(propylamino)propoxy]phenyl -3-phenylpropan-l-one, is a conunonly used sodium and potassium channel blocker for the treatment of ventricular tachycardia and atrial fibrillation [15]. Propafenone hydrochloride is a class IC antiarrhy tmic agent that shows structural similarity and activity related to p-adrenoly tic agents. The drug is efficacious in suppressing supraventricular and ventricular rhythm disorders [15] (Figure 14.12). 

The addition of methylmagnesium iodide to 2-phenylpropanal is stereoselective in producing twice as much syn-3-phenyl-2-butanol as the anti isomer (entry 5). The stereoselective formation of a particular configuration at a new stereogenic center in a reaction of a chiral reactant is called asymmetric induction. This particular case is one in which the stereochemistry can be predicted on the basis of an empirical correlation called Cram s rule. The structural and mechanistic basis of Cramls rule will be discussed in Chapter 3. 

When the 5-phenyltetrahydro-l,3-thiazine-2,4-dione 155 is treated with NaBH4, the thiazine ring fragments to produce (3 )-3-mercapto-3-phenylpropan-l-ol in 45% yield and the oxazolidin-2-ones 156 and 157 as a mixture of diastereomers (Equation 11) <2006TL1153>. 

Phenylchrom-2-ene results when 3-(2-hydroxyphenyl)-l-phenylpropan-l-one is treated with p-toluenesulfonic acid with continuous removal of water (71JOC600). The product is unstable, forming a tar over several hours. 

The 3,7-dinitrodiazocines 389a,b were obtained by one-pot synthesis in good yields from the reaction of 1,3-dinitro-2-phenylpropane with formaldehyde and methylamine or 2-aminoethanol with a considerable excess of both formaldehyde and the amine (1 7 9) (Equation 17) <2001RCB753>. 

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