1-Chloro-4-phenyl-2-butanone

Diazomethane is prepared as described in Org. Synth., Coll. Vol. /V1963, 250, with 50 g of Diazald (from Aldrich Chemical Company, Inc.) in 300 mL of ether added to 15 g of KOH in 25 mL of water, 30 mL of ether, and 50 mL of 2-(2-ethoxy-ethoxy)ethanol. One equivalent of diazomethane becomes incorporated in the reaction product, and the remainder serves as a scavenger for the HCI produced as a reaction by-product. The excess of diazomethane called for in this procedure is necessary to inhibit the undesired formation of 1-chloro-4-phenyl-2-butanone. The submitters report that this reaction can be performed on twice this scale with comparable results. 

The high rate of stirring reduces the production of 1-chloro-4-phenyl-2-butanone, a by-product of this reaction. 

A pure sample of diazo ketone can be obtained by chromatography on silica gel using 15% ethyl acetate/hexane as an eluent, Rf = 0.37. The checkers estimate the purity of the crude diazo ketone to be 90-91% based on careful column chromatography of 1 0-g aliquots. They further estimate that approximately 5-6% of 1 -chloro-4-phenyl-2-butanone is also produced in the reaction. The spectral properties of 1-diazo-4-phenyl-2-butanone are as follows 1H NMR (300 MHz, CDCI3) 8 2.59-2.64 (m, 2 H), 2.95 (t, 2 H, J = 7) 5.20 (broad s, 1 H), 7.17-7.31 (m, 5 H). 

The checkers found that on this scale a bulb-to-bulb (Kugelrohr) distillation could also be employed. The distilled product is contaminated with approximately 4-5% of 1 -chloro-4-phenyl-2-butanone which was produced in Step A. This impurity is easily removed by recrystallization from hexane. Alternatively, this impurity can be removed at the diazo ketone stage by column chromatography. The use of purified diazo ketone in Step B affords purer distilled product, but this modification has no significant effect on the overall yield. 

One approach that avoids the release of potent electrophiles into the general cellular milieu is use of the quiescent affinity label.1131 These evolved from the classic (non-quiescent ) affinity labels such as L-l-chloro-3-tosylamido-4-phenyl-2-butanone (Fig. 7a)... 

Z)-4-chloro-3-methyl-l-phenyl-I-butanone oxime yield 41%... 

The higher rate of HC1 elimination of 4-chloro-l-phenyl-1-butanone with respect to 5-chloro-2-pentanone by a factor of 9.9 confirmed the participation of the C=0 group. The 7r-electron delocalization of the benzene ring increases the basicity and nucleophilicity of the carbonylic oxygen and led to greater stabilization of the transition state through assistance to the C—Cl bond cleavage in the transition state (equation 80). 

C10H11CIO 4-chloro-1-phenyl-1-butanone 939-52-6 526.65 46.451 2 19365 C10H12 cis-1-methyl-2-(1-propenyl)benzene 2077-33-0 465.57 40.815 2... 

In the past ten years, there has been developed a series of enzyme inhibitors that combine the features of an alkylating agent with specificity for the active site of an enzyme, thus permitting alkylation and identification of a group at or near the active center of an enzyme, or a particular enzyme to be specifically inactivated. Thus a l-chloro-4-phenyl-3-p-toluenesulfonamido-2-butanone ( W-p-tolylsulfonylphenylalanine chloro-methyl ketone ) inactivates chymotrypsin (which cleaves a peptide bond adjacent to an aromatic residue), and 7-amino-l-chloro-3-p-toluene-sulfonamido-2-heptanone ( a-iV-p-tolylsulfonyllysine chloromethyl ketone ) inhibits trypsin (which cleaves a peptide bond adjacent to lysine. In both cases, a histidine residue at the active site is alkylated, and neither inhibitor will inhibit the other enzyme at low concentrations. 

The condensation of l-chloro-3-diazopiopanone (57) with aldehydes provides epoxy diazo ketones (equation 18). Treatment of a methanolic solution of (57) and benzaldehyde, in a stoichiometric ratio, with aqueous sodium hydroxide furnishes l-diazo-3,4-epoxy-4-phenyl-2-butanone (59a) in 69% yield the rrans-epoxide is obtained stereoselectively, analogous to the Darzens condensation of benzaldehyde and chloroacetone. The reaction is reported to proceed to give also the diazo ketones (59b-59e), and the epoxides obtained are exclusively of the trans configuration. ... 

Obtained by reaction of l-bromo-3-phenyl-propane with resacetophenone in the presence of potassium carbonate in refluxing acetone for 24 h. The 1-chloro derivative and butanone can also be used iustead of the mentioned starting materials (83%) [3204],... 

Fig. 8 Asymmetric reduction of JV-(tert-bnloxycarbonyl)-(35)-3-amino-l-chloro-4-phenyl-2-butanone and one-pot procedure fOT the synthesis of chiral epoxide...

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