Studies On The Amidocarbonylation Combined With Enzymatic Resolution And Synthesis Of Temperature Sensitive Dyes

In the first part of this dissertation, enantiomerically pure α - amino acids and their derivative were prepared by two-step chemoenzymatic synthesis. In the first step of the sequence, an aldehyde, amide and carbon monoxide react via amidocarbonylation catalyzed by palladium catalyst to afford the racemic N-acyl amino acid . In the second step , enzymatic enantioselective hydrolysis of the racemic N-acyl amino acid produces the optically pure α - amino acid and the other enantiomer as the N-acyl derivative.In the present work, palladium chloride was utilized as the chief catalyst instead of the expensive palladium bromide in the amidocarbonylation of isovaleraldehyde. Meanwhile the influence of some important parameters on the reactivity was discussed. Under the optimized reaction conditions, the isolated yield of N-acylleucine was 66.4%. The amidocarbonylation of other aldehydes such as propionaldehyde , butaldehyde , phenylaldehyde were also performed on the optimized condicions and the corresponding isolated yields of products were 30-70%.In the present study, the racemic N-acetylleucine obtained from palladium chloride catalyzed amidocarbonylation was resolved by the acylase-catalyzed enantioselective hydrolyzation, subsequently, more than 40% mol productivity of L-leucine and D-N-acetylleucine were obtained, and 99% ee L-leucine and 89% ee D-N-acetylleucine were achieved.In the second part of this dissertation the syntheses of temperature sensitive dyes, including LCV ( Leuco Crystal Violet) in triarylmethane compounds, CVL (Crystal Violet Lactone), Blue-502, Blue-63, S-Blue in phthalide compounds and TH-107 in fluorine compounds, were investigated..Temperature sensitive dye could generate molecular rearrangement and color change by controlling temperature, solvent polarity, system pH value. Many organic temperature sensitive dyes could occur tautomerism to generate molecular rearrangement, such as acid-base, ketone-enol tautomerization, which increases conjugated double bonds and forms new chromophoric system from colorless tocolored or from one color to the another color.In the present work, for the preparation of LCV /?-dimethylaminobenzaldehyde was generally prepared by the Vilsmeyer process, and then condensed with two molecular N,N-dimethylaniline to obtain LCV with 85% yield. As regards the synthesis of CVL, the convenient Michler's hydrol process was chosen which consisted tetramethyl Michler's hydrol condensing with m-dimethylbenzoid acid in the presence of sulfuric acid to prepare LCVL (Leuco Crystal Violet Lactone) that could oxidized to CVL by potassium persulfate in 75.2% yield. In the case of synthesis of Blue -502, 2-Methylindole was utilized to react with ethyl bromide to produce 1 -ethyl-2-methylindole catalyzed by tetrabutylammonium bromide, then N'N-diethylaniline was utilized to condense with phthalic anhydride to prepare ketone acid intermediate in the presence of anhydrous aluminium trichloride. Finally l-ethyl-2-methylind-ole condensed with ketone acid intermediate in acetic anhydride to obtain Blue-502(64% yield). For the synthesis of Blue-63, /n-Diethylaminophenol was used to be etherified to m-diethylaminophene-tole by ethyl bromide, and then l-ethyl-2-methyl which was prepared in the synthesis of Blue-502 was utilized to condense with quinolinic anhydride to prepare aza ketone acid intermediate in the presence of anhydrous zinc dicholoride. Finally w-diethylaminophenetole condensed with aza ketone acid intermediate in acetic anhydride to obtain Blue-63(72% yield). For the synthesis of S-Blue, 2-methylindole was utilized to react with dimethyl sulfate to prepare 1,2-dimethylindole catalyzed by tetrabutylammonium bromide, and then 1,2-dimethylindole was used to condense with phthalic anhydride to prepare ketone acid intermediate under the condition of the presence of anhydrous aluminium trichloride. Finally N,N-diethylaminotoluene condensed with ketone acid intermediate in acetic anhydride to obtain 75% yield of S-Blue. Finally for the synthesis of TH-107, o-Chloroaniline is utilized to react with hydroquinone in orthodichlorobenzene to obtain 2-chloro-4'-hydroxydiphenylamine catalyzed by phosphoric acid, and then 2-chloro-4'-hydroxydiphenylamine was derivated to 2-chloro-4'-methoxydiphenyla-Mine. Finally 2-chloro-4'-methoxydiphenylamine condensed with 4'-dibutylamino-2' -hydroxybenzophenone-2-carboxylic acid which was purchased in the presence ofconcentrated sulfuric acid to obtain TH-107 with yield of 58%.