1-phenylethyl acetamide

The mixture was cooled to room temperature and fdtered through a glass sinter. The filtrate was concentrated and then purified by column chromatography on silica gel (1/1 M-hexane/ethyl acetate) to give A/-((/ )-l-phenylethyl)acetamide (119 mg, 0.73 mmol, 92 %, 98 % ee). 

Fig. 8.3 Lipase-catalyzed formation of 2-methoxy-/V-[(7/ )-l-phenylethyl]-acetamide (III) and fSj-phenylethylamine (IV). The reaction uses racemic 1-phenylethylamine (I) and ethylmethoxyacetate (II) as educts and is carried out in methyl-tert-butylether. As a byproduct, ethanol is formed.

The use of MALDI-MS for the measurement of low molecular mass compounds is widely accepted now [61], but quantification remains problematic. The main problem is the inhomogeneous distribution of the analytes within the matrix [62]. This leads to different amounts of ions and therefore to different signal intensities at various locations of a sample spot. The simplest and most effective way to overcome this problem is the use of an appropriate internal standard [63]. The use of deuterated compounds with a high molecular similarity to the analyte as internal standards leads to a linear correlation between relative signal intensities and relative amount of the compound to be quantified (Fig. 4b) [64]. Using this approach it is possible to quantitate substrates and products of enzyme catalyzed reactions. Two examples were shown recently by Kang and coworkers [64, 65]. The first was a lipase catalyzed reaction which produces 2-methoxy-N-[(lR)-l-phenylethyl]-acetamide (MET) using rac-a-... 

Fig. 4. a rac-Phenylethylamine (PEA) and 2-methoxy-J T-[(li )-l-phenylethyl]-acetamide (MET) are substrate and product in a lipase catalyzed transesterification, b Linear relationship between relative signal intensities in MALDI-MS and the relative concentrations of PEA/d5-labeled PEA. c Comparison of decrease in PEA during enzymatic conversion as measured by quantitative MALDI-MS and gas chromatography (GC)... 

Problem 31.29 Outline the synthesis of N-(2-phenylethyl)acetamide from toluene and aliphatic and inorganic reagents. 

Substrates in which the amino group is protected as ait amide or urethane also show anti selectivity. The degree is not generally so large [e.g., d.r. 77 23 for A -(2-hydroxy-l-methyl-2-phenylethyl)acetamide] but can be satisfactory with some substrates [e.g., d.r. 90 10 for lert-butyl (35,4T(,55)-4-r 7-butoxyearbonylamino-3-hydroxy-5-inelhylhcptanoate]. 

N-(2-phenylethyl)acetamide in the presence of a Lewis acid and heat (the Imown syntiiesis of l-methyl-3,4-dihydroisoquinoline) (72). 

The Bischler-Napieralski synthesis of l-methyl-3,4-dihydroisoquinoline (18) from N-(2-phenylethyl)acetamide (19) in the presence of heat and acid (72) was not predicted by the Electrophilic Aromatic module of CAMEO this module of CAMEO predicted instead the formation of methyl 2-acetyl-phenethylamine, 20 (Scheme 5). In a related case, CAMEO predicted (when the Electrophilic Aromatic module was chosen) that 4-anilino-butan-2-one (21) would undergo intramolecular cyclization to form 4-hydroxy-4-methyl-tetrahydroquinoline, 23 (Scheme 6). Apparently, CAMEO correcdy perceives the eneamine character of 21 as necessary for this reaction to occur. It was noted in this case that ring formation, as predicted by CAMEO, depended upon the presence of mineral acid, but did not occur if a Lewis acid (e.g., stannic chloride) was selected instead as the reagent. It is known, however, that intramolecular cyclization of 21 does occur in the presence of a Lewis acid and yields 4-methyl-quinoline, 22, as product (74). 

Scheme 5. Synthesis of l-Methyl-3,4-dihydroisoquinoline (18) from N-(2-Phenylethyl)acetamide (19)...

LHASA pr icted that l-methyl-3,4-dihydroisoquinoline (18) could be synthesized from methyl phenyl N-(2-chloroetiiyl)imine via a Friedel-Crafts alkylation in the presence of a Lewis acid and heat. This prediction was based on a literature reference identified by LHASA. LHASA also predicted the Bischler-Napieralski synthesis of 18 from N-(2-phenylethyl)acetamide (19) in the presence of heat and acid (Scheme 5). 

The known free-radical decomposition of aryl nitrosoamides (ArN(NO)COR ) and the report that nitrosoamides of 0-alkyl-hydroxylamines decompose by a free-radical pathway indicate that free-radical processes might occur in the normal nitrosoamide decomposition. In fact, the aliphatic nitrosoamides have been used as initiators at elevated temperatures for the polymerization of styrene and other olefins At, or near, room temperature, however, it appears that free radicals are not formed in the nitrosoamide decomposition. It has been found, for example, that (1) COj (a product of the decarboxylation of carboxyl radicals) is not formed in the decomposition (2) the scavenger nitric oxide has no effect on the reaction (3) normal products and no polymer are formed in the decomposition of A -(i-butyl)-A -nitrosobenzamide ° ° and N-nitroso-7V-(l-phenylethyl)acetamide -in styrene and (4) no difference in acetate yields is observed when A -nitroso-A-(1-phenyl-ethyl) acetamide is decomposed in benzene in the presence or absence of 0-1 m Styrene and 1-phenylethyl acetate react with... 

Amides derived from carboxylic acids (8-144) and the corresponding JV-substituted (8-145) and JV,JV-disubstituted amides (8-146) are polar compounds of low volatility, yet some of them may participate in the aroma of non-acidic foods. Commonly occurring compounds are mainly amides derived from formic and acetic acids. For example, beer contains hundredths to tenths mg/kg JV-methylformamide (8-145, R= H, RY CHj), JV-methylacetamide (8-145, R = rY CHj), JV ,Y-dimethylacetamide (8-146, R= R = R = CHj), JV -(2-methylbutyl)acetamide,whereR= CH3,R = CHjCH (CHj) CH2CH3, its isomer JV-(3-methylbutyl)acetamide, R = CH2 CH2CH(CHj)2 and JV -(2-phenylethyl)acetamide (8-147), which are produced by condensation of carboxylic acids with amines followed by decarboxylation (Figure 8.70). Many non-volatile JV-substituted formamides and acetamides are also produced in the Maillard reaction. Decarboxylation of asparagine catalysed by decarboxylases yields 3-aminopropionamide (8-148), which may become a precursor of acrylamide (see Section 12.2.2). 

In a recent publication, DKR of rac-l-phenylethylamine was optimized to be applicable on a multigram scale [91]. This is of great importance for industrial applications. The para-methoxyphenyl derivative of the Shvo catalyst was used for the racemization. It was found that on a 45 mmol scale, the catalyst loading could be decreased to only 1.25 mol%. For the enzymatic resolution, 10 mg CALB/mmol of substrate was used. With methyl methoxyacetate as the acyl donor, (R)-2-methoxy-W(l-phenylethyl)acetamide was obtained with 98% ee and in 83% isolated yield. 

Martinez, E., Estevez, J.J.C., Estevez, R.J.J., and Castedo, L., PhotochemicaUy induced cyclization of N-[2-(o-styryl) phenylethyl]acetamides and 5-styryl-l-methyl-1,2,3,4-tetrahydroisoquinolines new total syntheses of l-methyl-l,2,3,4-tetrahydronaphtho[2,l-f]isoquinolines. Tetrahedron, 57, 1981, 2001. 

Acetamide, 2-amino-N-(2-hydroxy-1 -methyl-2-phenylethyl)-N-methyl-, [R-(R, R )]-, 4-Pentenoic acid, 2-amino-, (R)- and 4-Pentenoic acid, 2-[[(1,1-dimethylethoxy)carbonyl]amino]-, (R)-)... 

Carcerand 51 is much more soluble than 50 due to eight 2-phenylethyl substituents [41], During its synthesis a template effect by various solvent molecules was observed. Thus cyclizing the precursor in dimethyl sulfoxide, dimethyl acetamide, and dimethyl formamide gave the corresponding carceplexes 51 G in 61%, 54%, and 49% yields, respectively (i.e. the interior of the carcerands was occupied by one solvent molecule). 

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