Master of Science (MS)
Semester of Degree Completion
Edward M. Treadwell
Cinnamaldehyde semicarbazone was varied in three ways, by altering the ring, the conjugated linker, and the semicarbazone, to investigate how changing the structure affects the photochomicity. The synthesis of 7 hetero- and 2 polycyclic- aromatic semicarbazone variants involved three steps, (a Wittig reaction, hydrolysis, and condensation to the semicarbazone) with cumulative yields of 15% to 52%. Generally, the pyridine series gave lower yields than other synthesized semicarbazones. The Wittig reaction gave cis/trans mixtures in ratios of 2 : 1 to 1 : 7 for the 6 acetals, except for the 3 that went directly to the aldehyde, due to the acidity of the silica gel. The final products were recrystallized, which is part of the reason for the low yield. The structure and purity of all compounds involved was confirmed by 1H NMR and 13C NMR spectroscopy.
The synthesized semicarbazones were characterized by UV-Vis spectroscopy using 1 : 1 dichloromethane : acetonitrile. Two major absorption bands were observed, one between 220nm and 230nm, and the other one around or above 300nm. The band around 220nm-230nm was not affected by differences in the ring, however, for most compounds, the band above 300nm shifted to longer wavelength. Two of the semicarbazones, those of 3-(3-pyridinyl)-prop-2-enal (311nm) and 3-(3-indolyl)- prop-2-enal (305nm), did not show a shift to the longer wavelength. Moderate shifts were seen for the semicarbazones of 3-(2-pyridinyl)-prop-2-enal (316nm) and 3-(2-furyl)-prop-2-en-1-al (318nm). The greatest shifts were seen for the semi- carbazones of 3-(4-pyridinyl)-prop-2-enal (323nm), 3-(2-thienyl)-prop-2-enal (327nm), 3-(1-naphthyl)-prop-2-enal (336nm), and 3-(9-anthracenyl)- prop-2-enal (413nm).
To investigate the photochromicity of the synthesized semicarbazones, the UV-Vis spectra of "light" and "dark" forms of the semicarbazone were compared. Two known photochromic semicarbazones (cinnamaldehyde semicarbazone and omethoxycinnamaldehyde semicarbazone) were used as references. All nine synthesized semicarbazones exhibited photochromicity except 3-(2-furyl)-prop-2- en-1-al semicarbazone. Among the 8 photochromic semicarbazones, the thiophene derivative exhibited an obvious photochromicity with a new peak that appeared in the dark form. All other compounds exhibited photochromicity as an increased ratio (by 0.4 to 2.0) for the 220 : 300 nm absorptions. The UV-VIS spectrum of 3-(2-thiophenyl)prop-2-en-1-al semicarbazone sample was reacquired after the "dark" sample had been exposed to light, and it exhibited a reversible photochromicity. The spectra in pure acetonitrile was also obtained, but they did not show any differences between the "light" and "dark" form. In Lin's paper, differences between the "light" and "dark" forms were seen by 1H NMR, however, no differences between the spectra of "light" and "dark" forms of the semicarbazones in this study were observed.
The extended conjugated linker was synthesized from cis-but-2-en-1,4-diol by a procedure based on previous studies by both Saathoff and Sun. After mono- protection with an acetate group (82%), the remaining hydroxy group was converted to a halide (Br: 81 %; I: 61 %) and followed by an Arbuzov reaction (Br: 31 %, I: 65%). The phosphonate underwent hydrolysis of acetate group (47%) and oxidation to the aldehyde (52%) to give trans-4-(diethylphosphono)-2-butenal in a 5% (Br) and 8% (I) cumulative yields. The monoprotection had to be carried out in an ice bath, with the slow addition by syringe of the less than 1eq acetyl chloride, to avoid diacetylation. The iodide behaved better than bromide in the Arbuzov reaction, though the iodide had to be synthesized via the mesylate. Direct conversion of the alcohol to phosphonate was tried based on Wiemer's procedure, but it did not give the expected compound. Based on the 1H NMR spectra, there was cis-trans isomerization and loss of the acetate group occurring in the reaction. Before oxidation, the alcohol must be purified in order to obtain product.
Two synthetic ways were explored to prepare the modified semicarbazide moiety. Three ureas (phenylurea, 2,5-dimethoxyphenylurea and 4-methoxyphenylurea) were synthesized successfully with high yields of 69%- 90% from aniline and sodium cyanate. Melting point analysis, IR, 1H NMR and 13C NMR spectroscopy confirmed the purity and identity of these compounds. At least twenty different conditions were attempted to convert the urea to the semicarbazide using hydrazine monochloride or hydrazine sulfate with different additives (NaOH, HCl, PPTs etc.) and different solvent system. However none of these gave complete conversion to the semicarbazide, and collectively, six different NMR spectra were obtained from these attempts. An HPLC comparison of two of these reactions showed that the major component was the urea, and the minor components were the same both. So instead, the carbamate of 2,5-dimethoxyaniline was synthesized using ethyl chloroformate and NaH in a yield of 95%. This was successfully converted to the semicarbazide in a yield of 23%.
Xiao, Xiao, "Investigations Towards Synthesis of Cinnamaldehyde Semicarbazone Derivatives and Their Photochromicity by Modifying the Ring, the Linker, and the Semicarbazone" (2014). Masters Theses. 1308.