Microwave-Assisted Synthesis of Isopropyl <i>β</i>-(3,4-Dihydroxyphenyl)-<i>α</i>-hydroxypropanoate

Zhang, Qun-Zheng; Tian, Xue-Feng; Du, Guan-Le; Pan, Qing; Wang, Yi; Zhang, Xun-Li

doi:https://doi.org/10.1155/2013/505460

Journal of Chemistry

On this page

Abstract Introduction Results and Discussion Experimental Conclusions Acknowledgments References Copyright Related Articles

Research Article | Open Access

Volume 2013 | Article ID 505460 | https://doi.org/10.1155/2013/505460

Microwave-Assisted Synthesis of Isopropyl β-(3,4-Dihydroxyphenyl)-α-hydroxypropanoate

Qun-Zheng Zhang,^1,2Xue-Feng Tian,¹Guan-Le Du,¹Qing Pan,³Yi Wang,¹and Xun-Li Zhang^1,2

Academic Editor: Matthias D'hooghe

Received14 May 2013

Revised17 Jul 2013

Accepted05 Aug 2013

Published08 Sept 2013

Abstract

Using microwave irradiation heating, isopropyl -(3,4-dihydroxyphenyl)--hydroxypropanoate was synthesised from 3,4-dihydroxybenzaldehyde and acetylglycine through the formation of 2-methyl-4-(3,4-acetoxybenzylene)oxazol-5-ones, -acetylamino--(3,4-diacetoxyphenyl)acrylic acid, and -(3,4-dihydroxyphenyl)pyruvic acid followed by Clemmensen reduction and esterification. The reaction conditions in terms of operating parameters were optimised by using an orthogonal design of experiment (ODOE) approach, including reaction temperature, reaction time, and microwave power level. Compared with conventional heating, the reaction time was significantly reduced for all reactions and the product yields were increased (except for the third-step reaction) under microwave heating conditions. The most remarkable microwave enhancement was found in the step of isopropyl -(3,4-dihydroxyphenyl)--hydroxypropanoate production where the reaction time was reduced from 10 hrs (conventional heating) to 25 mins (microwave heating) whilst the yield was increased from 75.6% to 87.1%, respectively.

1. Introduction

Recent studies have demonstrated the pharmaceutical activity of isopropyl β-(3,4-dihydroxyphenyl)-α-hydroxypropanoate against cerebral ischemia and hypobaric hypoxia of high altitude [1–4]. As a result, chemical synthesis of this compound and its derivatives has been of great interest. The most commonly used method for synthesising this compound involved the preparation of 2-methyl-4-(3,4-acetoxybenzylene)oxazol-5-ones, α-acetylamino-β-(3,4-diacetoxyphenyl)acrylic acid, and β-(3,4-dihydroxyphenyl)pyruvic acid which was reduced via Clemmensen reaction that was followed by final esterification [2, 5] under the conventional heating conditions. Other synthesis routes were also explored, for example, by taking steps of benzyl protection, Darzens reaction, selective ring opening by Lewis acid, reduction, and, finally, catalytic hydrogenation [4]. However, those methods suffered from low yield, poor reproducibility, and a long reaction time.

Owing to its advantages over the conventional heating method, microwave heating has been applied to a wide range of organic synthesis processes [6–9], following the pioneering work by Gedye et al. [10] and Giguere et al. [11] in the 1980s. The main advantages include the acceleration of reaction rate [12–14], improved product selectivity [15–18], and high yield [18–20]. The application of microwave heating has also been explored in the field of organic synthesis for drug discovery [21, 22]. In our previous study, we employed a microwave heating method for the synthesis of Danshensu, which is an active compound/ingredient in a traditional Chinese herbal medicine Danshen (Salvia miltiorrhiza); we observed improved yields with shorter reaction time compared with conventional heating [23]. For the optimisation of experimental conditions, design of experiments (DOE) has been used as a powerful approach to reduce the variation in a process and, ultimately, to produce high quality product at low cost for manufacturing [24, 25]. Among various DOE approaches, the Taguchi method [26] has been frequently employed to investigate the effect of different parameters on the mean and variance of a process performance characteristics which defines how well the process is functioning; it generally involves using orthogonal arrays to organise the parameters affecting the process and the levels at which they should be varied [25, 27].

In the present study, we extended the microwave-assisted method to the synthesis of isopropylβ-(3,4-dihydroxyphenyl)-α-hydroxypropanoate (Scheme 1). A design of experiments via Taguchi method was used to determine the influencing factors and levels in order to optimise the product yield; the factors included reaction temperature, reaction time, and microwave power level.

2. Results and Discussion

2.1. Selection of Operating Reaction Parameters

The main focus of this study was to investigate the effect of microwave radiation heating on the four-step synthesis process in comparison to conventional heating method. The reaction conditions were initially examined by varying reaction temperature, reaction time, and microwave radiation input power level in order to determine the variable range. Based on the initial results, an orthogonal experimental design was carried out, and the three experimental factors at three levels for each synthesis step are shown in Table 1.

2.2. Synthesis of 2-Methyl-4-(3,4-acetoxybenzylene)oxazol-5-ones

With the determination of experimental factors and levels shown in Table 1 experiments were carried out following the orthogonal test programs, L₉(3³). The experimental results are summarised in Table 2. All yields shown in the tables are the mean value of three experiment runs. The experimental data was analysed with statistical software Minitab 16, and the ANOVA results are shown in Table 3.

The variance analysis showed that all three factors had insignificant impact on reaction yields at the selected level ranges as all three P values were greater than 0.05. However, the order of influencing factors was C > B > A, indicating that the microwave radiant power was the dominant influence among the three. The highest yield of 89.7% was obtained under the conditions of A₂B₂C₃ among the nine experiment runs. The design of experiment suggested the optimised conditions of A₂B₂C₂, and using that optimisation a yield of 90.8% was obtained in the experiment. That confirmed the optimised reaction conditions of A₂B₂C₂ for the microwave synthesis of 2-methyl-4-(3,4-acetoxybenzylene)oxazol-5-ones.

2.3. Synthesis of α-Acetylamino-β-(3,4-diacetoxyphenyl)acrylic Acid

Table 4 shows the orthogonal test programs, L₉(3³), and test results for the synthesis of α-acetylamino-β-(3,4-diacetoxyphenyl)acrylic acid under microwave heating conditions. The ANOVA results are shown in Table 5.

The variance analysis also showed that all three factors had no significant impact on reaction yields at the selected level ranges where all three P values were greater than 0.05. However, the order of influencing factors was found to be C > B > A, suggesting that the microwave radiant power was the dominant influence among the three. The best experiment result (i.e., yield 87.5%) from the nine experimental runs was obtained under the reaction of A₁B₃C₃. The optimum conditions found from the design of experiment were A₂B₁C₃, based on which the experiment was carried out reaching a yield of 88.6%, which was higher than that under all nine experiment conditions. This confirmed that the reaction conditions of A₂B₁C₃ to be the optimised conditions for the microwave synthesis of α-acetylamino-β-(3,4-diacetoxyphenyl)acrylic acid.

2.4. Synthesis of β-(3,4-Dihydroxyphenyl)pyruvic Acid

It was interesting to note that this step of synthesis required a relatively higher microwave power level. The product was not obtained until a power level of 900 W was applied. Therefore, the power level of 900 W was set throughout the experiment. Table 6 summarises the results at different temperatures for a given reaction time of 30 mins.

Further experiments for different reaction time periods were carried out to explore the highest possible yields. The results are shown in Table 7. It was observed that with increasing reaction time the yield increased. However, when the reaction time exceeded 30 mins, the yield remained approximately constant. This indicated that the highest yield was reached under the reaction conditions of 90°C for 30 mins at a microwave power level of 900 W.

2.5. Synthesis of Isopropyl β-(3,4-Dihydroxyphenyl)-α-hydroxypropanoate

The orthogonal test programs, L₉(3³), and test results for the synthesis of isopropylβ-(3,4-dihydroxyphenyl)-α-hydroxypropanoate are summarised in Table 8, and the ANOVA results are shown in Table 9.

The variance analysis showed that the three factors had insignificant impact on reaction yields in the chosen level ranges; however, the order of influence was B > C > A; indicating the reaction time to be the dominant factor. The best experiment result (i.e., a yield of 86.1%) from the nine reaction runs was observed under the conditions of A₂B₃C₁. However, the design of experiment suggested the optimised experimental conditions of A₃B₃C₂. To address the seemly contradictory results in terms of reaction conditions, further three experimental runs were conducted under the ODOE-suggested optimal conditions, and the highest yield of 87.1% was obtained. With that yield (i.e., 87.1%) ODOE was checked which confirmed the optimised microwave reaction conditions of A₃B₃C₂ for the synthesis of isopropylβ-(3,4-dihydroxyphenyl)-α-hydroxypropanoate.

It should be noted that the initial design of the reaction time was 10, 20, and 30 mins at microwave power levels of 100, 300, and 500 W, respectively. However, it was found that with 500 W for 30 mins, the reaction product became black due to overheat which was likely attributed to the presence of metallic catalyst zinc amalgam used in this experiment. Therefore, the final reaction time at high power level (i.e., 500 W) was reduced to 25 mins.

2.6. Comparison of Microwave and Conventional Heating Methods

It is generally understood that the process of microwave radiation heating is different from conventional heating in terms of heat generation and energy transfer [6, 28]. Firstly, microwave heating is a volumetric process and sometimes referred to as “interior heating” where heat can be generated throughout the sample, whilst most of conventional heating relies on conduction and/or convection [29]. This can result in a shorter microwave reaction time due to the quicker heatingup. Secondly, microwave heating is “selective” depending on the materials dielectric properties, suggesting that some microwave strong absorbers can reach higher temperatures than others [29, 30]. This allows to generate possible spatial “hot-spots,” for example, on catalyst active sites, leading to an apparent reaction rate acceleration with reference to that at the measured overall temperature. On the other hand, the “selective” heating may also lead to an apparent reaction slowdown where the reaction active sites have lower temperature than the overall temperature.

Table 10 compares the reaction time and yield for the four-step reactions. As can be seen from the Table, it took 5 hrs to carry out the synthesis of azolactone in conventional heating with a yield of 80.0%, while 15 mins with microwave heating gave a yield of 90.8%. Similar results were observed for the synthesis of α-acetylamino-β-(3,4-diacetoxyphenyl)acrylic acid. More remarkably was the synthesis of isopropylβ-(3,4-dihydroxyphenyl)-α-hydroxypropanoate under microwave heating conditions to take 25 mins reaching a yield of 87.1% compared to the conventional heating of 10 hrs for a yield of 75.6%. This was likely due to the addition of zinc-mercury amalgam catalyst which is a strong microwave absorber.

For the synthesis of β-(3,4-dihydroxyphenyl) pyruvic acid a shorter reaction was observed with microwave heating. However, the yield under microwave heating conditions was lower than that with conventional heating which may be attributed to the different dielectric properties of the reagents. However, to get a deeper insight into the mechanism of this process further investigation is required.

3. Experimental

3.1. Materials and Apparatus

3,4-Dihydroxybenzaldehyde (CP) was purchased from Guangxi Chemicals Import and Export Ltd. N-acylglycine (AR) and acetic anhydride (AR) were purchased from Xi’an Chemical Reagent Factory. Mercury chloride (AR) was supplied by Shanghai Shanpu Chemical Reagent Co., Ltd, and Zinc granular (AR) by Xi’an Sanpu Chemical Reagent Co., Ltd. Isopropanol (AR) was obtained from Tianjin Chemical Reagent Factory 6.

All microwave-assisted reactions were carried out using a WF-400 Microwave Reaction System (Shanhai Yiyao Analytical Instruments Ltd.) operated at atmospheric pressure. A WRS-1A digital melting point instrument (Shanghai Precision and Scientific Instrument Co., Ltd.) was used for melting point measurements. An RE-52AA rotatory evaporator (Shanghai Rong Biochemical Instrument Factory) and a DZ1-BC vacuum oven (Tianjin Tester Instrument Co., Ltd.) were also used for the experiment. Chemical analysis was performed by both NMR (INOVA-400 MHz, Varian) and infrared spectroscopy (FT-IR360, Nicolet Instrument Co., USA).

3.2. Preparation of 2-Methyl-4-(3,4-acetoxybenzylene)oxazol-5-ones

A mixture of 3,4-dihydroxybenzaldehyde (13.8 g, 0.1 mol), N-acylglycine (14.2 g, 0.13 mol), and anhydrous NaOAc (10.7 g, 0.13 mol), Ac₂O (51.2 g, 0.5 mol) was made in a 150 mL double-neck flask. The flask was connected to the microwave reactor system equipped with magnetic stirrers, a reflux condenser and high precision platinum resistance temperature sensors, which was linked with the temperature control system. In a typical process of microwave-irradiated reactions, when the microwave was switched on, the temperature started to rise until it reached the preset level whilst the reaction timing started to count. The temperature control system would switch on and/or cut off microwave irradiation in an intermittent way to keep the temperature in the rage of 0.1°C at the preset level.

The reaction was carried out in the microwave reactor system under preset conditions. Once the mixture turned into a dark yellow solution with temperature rising, the refluxing started and remained until solution turned dark brown. When cooling to room temperature 60 mL ice water was added, and the mixture was stirred until yellow crystals precipitated. It was then filtered, washed with cold water, and dried under vacuum to produce yellow crystals product A, 2-methyl-4-(3,4-acetoxybenzylene)oxazol-5-ones (mp 161.2–161.5°C, lit. [31] mp 161.0–161.4°C).

3.3. Preparation of α-Acetylamino-β-(3,4-diacetoxyphenyl)acrylic Acid

The above produced 2-methyl-4-(3,4-acetoxybenzylene)oxazol-5-ones (12.54 g, 0.04 mol) was mixed with acetone (46 mL) and water (46 mL) in a 150 mL double-neck flask, which was then attached to the microwave reaction system. With stirring and refluxing, the reaction solution turned dark brown, which was then decolorized using active carbon with microwave heating and refluxing. A vacuumed filtration step followed and resulted in a red solution. When cooling to room temperature needle-shaped yellow crystals formed from the solution, which were then washed with ice water and vacuum filtered resulting in compound B. The filtrate was further concentrated by evaporation, cooled and vacuum filtered to recover yellow product B, α-acetylamino-β-(3,4-diacetoxyphenyl)acrylic acid (mp 188.8–189.4°C, lit. [31] mp 188.9–189.1°C).

3.4. Preparation of β-(3,4-Dihydroxyphenyl)pyruvic Acid

A mixture of compound B (12.85 g, 0.04 mol) with 125 mL HCl (1 M) was made in a 250 mL double-neck flask, which was connected to the microwave reactor system. When the reaction finished, the light yellow solution was decolorized using active carbon with microwave heating and refluxing, followed by vacuumed filtration. The filtrate was concentrated through evaporation to form light yellow crystals which were further purified by filtration, washing, and drying for product C, β-(3,4-dihydroxyphenyl)pyruvic acid (mp 191.2–191.6°C, lit. [31] mp 191.4–191.6°C).

3.5. Preparation of Isopropyl β-(3,4-Dihydroxyphenyl)-α-hydroxypropanoate

The above synthesised β-(3,4-dihydroxyphenyl)pyruvic acid (1 g) was mixed with 5.5 mL concentrated HCl, 36 mL isopropanol, and 2 g zinc-mercury amalgam in a 100 mL double-neck flask which was connected to the microwave reactor system. Upon the completion of reaction, the reaction mixture was filtrated and distilled to remove catalyst and solvent. After adding 30 mL ethyl acetate, the solution pH was adjusted with saturated sodium bicarbonate to pH < 7 for phase separation. The brown oily phase was then dehydrated with NaS₂O₄ followed by filtration and vacuumed distillation for solvent removal. The product was further purified by hydrothermal recrystallisation to obtain light yellow powder product D, isopropylβ-(3,4-dihydroxyphenyl)-α-hydroxypropanoate (mp 79.2–80.0°C, lit. [4] mp 79.4–80.2°C).

4. Conclusions

Microwave radiation was employed as an effective heating method in the synthesis of a pharmaceutically active compound isopropylβ-(3,4-dihydroxyphenyl)-α-hydroxypropanoate. The reaction conditions were optimised by using an orthogonal design of experiment (ODOE) approach, and the operating parameters including reaction temperature, reaction time, and microwave power level were examined. Microwave heating was applied to all four reaction steps and compared to conventional heating method. It was found that the reaction time was significantly reduced for all reactions and the product yields were increased (except the third-step reaction) under microwave heating conditions. The most remarkable microwave enhancement was observed in the step of isopropylβ-(3,4-dihydroxyphenyl)-α-hydroxypropanoate production where the reaction time was reduced from 10 hrs (conventional heating) to 25 mins (microwave heating) whilst the yield was increased from 75.6% to 87.1%, respectively.

Acknowledgments

This work was financially supported by grants from Important Science & Technology Specific Projects of Innovative Program of Shaanxi Province (2010ZDKG-46), Scientific Research Plan Projects of Shaanxi Education Department (12JK0582; 12JK1012), Scientific Research Foundation for Ph.D. of Xi’an Shiyou University (2011BS010), and 2012 National Innovation and Entrepreneurship Training Project for College Students (201210705047).

References

X. L. Deng, X. M. Chen, F. S. Jiang, and X. C. Yiao, “Synthesis of Sodium β-(3, 4-Dihydroxyphenyl)lactate,” Chinese Pharmaceutical Journal, vol. 36, no. 9, pp. 523–524, 2005.
View at: Google Scholar
X. H. Zheng, Y. C. Zhang, S. X. Wang, and X. F. Zhao, “Preparation of isopropyl β-(3, 4-dihydroxyphenyl)-α-hydroxypropionate for treatment of cardiovascular and cerebrovascular diseases,” CN1583710, 2005.
View at: Google Scholar
X. H. Zheng, Q. Z. Zhang, S. X. Wang, and X. F. Zhao, “Beta-(3, 4) dihydroxy phenyl-alpha hydroxy borneol propionate, its synthesis method and use,” CN1868998, 2006.
View at: Google Scholar
Q. Zhang, Y. Dong, Y. Nan, X. Cai, and X. Zheng, “Synthesis of β-(3,4-dihydroxyphenyl)-α-hydroxy propionic acid esters,” Chinese Journal of Organic Chemistry, vol. 29, no. 9, pp. 1466–1469, 2009.
View at: Google Scholar
X. H. Zheng, Q. Z. Zhang, S. X. Wang, and X. F. Zhao, “Substituted β-phenyl-α-hydroxy-propanoic acid, synthesis method and use thereof PCT/CN2007/0011550,” US8017786, 2011; EP2019090, 2012; RU2421443, 2011; CAC07C69/732, 2011; AU2007250364, 2011; SG147841WO2007/131446, 2011; NZ572958, 2011; KR10-1059639, 2011., 2006.
View at: Google Scholar
C. O. Kappe, “The use of microwave irradiation in organic synthesis. From laboratory curiosity to standard practice in twenty years,” Chimia, vol. 60, no. 6, pp. 308–312, 2006.
View at: Publisher Site | Google Scholar
M. Gupta, S. Paul, and R. Gupta, “General characteristics and applications of microwaves in organic synthesis,” Acta Chimica Slovenica, vol. 56, no. 4, pp. 749–764, 2009.
View at: Google Scholar
A. M. Rodriguez, P. Prieto, A. de la Hoz, and A. Díaz-Ortiz, “‘In silico’ mechanistic studies as predictive tools in microwave-assisted organic synthesis,” Organic & Biomolecular Chemistry, vol. 9, no. 7, pp. 2371–2377, 2011.
View at: Publisher Site | Google Scholar
R. O. M. A. de Souza, L. S. de M., and M. Miranda, “Microwave assisted organic synthesis: a history of success in Brazil,” Quimica Nova, vol. 34, no. 3, pp. 497–506, 2011.
View at: Publisher Site | Google Scholar
R. Gedye, F. Smith, K. Westaway et al., “The use of microwave ovens for rapid organic synthesis,” Tetrahedron Letters, vol. 27, no. 3, pp. 279–282, 1986.
View at: Google Scholar
R. J. Giguere, T. L. Bray, S. M. Duncan, and G. Majetich, “Application of commercial microwave ovens to organic synthesis,” Tetrahedron Letters, vol. 27, no. 41, pp. 4945–4948, 1986.
View at: Google Scholar
A. M. Sajith and A. Muralidharan, “Microwave enhanced Suzuki coupling: a diversity-oriented approach to the synthesis of highly functionalised 3-substituted-2-aryl/heteroaryl imidazo[4,5-b]pyridines,” Tetrahedron Letters, vol. 53, no. 9, pp. 1036–1041, 2012.
View at: Publisher Site | Google Scholar
N. Gruber, M. C. Mollo, M. Zani, and L. R. Orelli, “Microwave-enhanced synthesis of phosphonoacetamides,” Synthetic Communications, vol. 42, no. 5, pp. 738–746, 2012.
View at: Publisher Site | Google Scholar
A. M. G. Silva, B. Castro, M. Rangel et al., “Microwave-enhanced synthesis of novel pyridinone-fused porphyrins,” Synlett, no. 6, pp. 1009–1013, 2009.
View at: Publisher Site | Google Scholar
M. A. H. Zahran, H. F. Salama, Y. G. Abdin, and A. M. Gamal-Eldeen, “Efficient microwave irradiation enhanced stereoselective synthesis and antitumor activity of indolylchalcones and their pyrazoline analogs,” Journal of Chemical Sciences, vol. 122, no. 4, pp. 587–595, 2010.
View at: Google Scholar
N. T. Hoai, A. Sasaki, M. Sasaki, H. Kaga, T. Kakuchi, and T. Satoh, “Selective synthesis of 1,6-anhydro-β-D-mannopyranose and -mannofuranose using microwave-assisted heating,” Carbohydrate Research, vol. 346, no. 13, pp. 1747–1751, 2011.
View at: Publisher Site | Google Scholar
H. Ichikawa, H. Ohfune, and Y. Usami, “Microwave-assisted selective synthesis of 2H-indazoles via double Sonogashira coupling of 3,4-diiodo-pyrazoles and bergman-masamune cycloaroma-tization,” Heterocycles, vol. 81, no. 7, pp. 1651–1659, 2010.
View at: Publisher Site | Google Scholar
P. Dao, C. Garbay, and H. Chen, “High yielding microwave-assisted synthesis of tri-substituted 1,3,5-triazines using Pd-catalyzed aryl and heteroarylamination,” Tetrahedron, vol. 68, no. 20, pp. 3856–3860, 2012.
View at: Publisher Site | Google Scholar
D. S. Bose and R. K. Kumar, “High-yielding microwave assisted synthesis of quinoline and dihydroquinoline derivatives under solvent-free conditions,” Heterocycles, vol. 68, no. 3, pp. 549–559, 2006.
View at: Publisher Site | Google Scholar
J. A. F. Joosten, N. T. H. Tholen, F. Ait El Maate et al., “High-yielding microwave-assisted synthesis of triazole-linked glycodendrimers by copper-catalyzed $[3 + 2]$ cycloaddition,” European Journal of Organic Chemistry, no. 15, pp. 3182–3185, 2005.
View at: Publisher Site | Google Scholar
M. Pastó, B. Rodríguez, A. Riera, and M. A. Pericàs, “Synthesis of enantiopure amino alcohols by ring-opening of epoxyalcohols and epoxyethers with ammonia,” Tetrahedron Letters, vol. 44, no. 46, pp. 8369–8372, 2003.
View at: Publisher Site | Google Scholar
U. M. Lindström, B. Olofsson, and P. Somfai, “Microwave-assisted aminolysis of vinylepoxides,” Tetrahedron Letters, vol. 40, no. 52, pp. 9273–9276, 1999.
View at: Publisher Site | Google Scholar
Q. Z. Zhang, T. He, X. Y. Xiong, G. Chen, and B. Y. Su, “Microwave assisted synthesis of Danshensu,” Chinese Chemical Reagents, vol. 3, no. 3, pp. 259–262, 2011.
View at: Google Scholar
F. Pukelsheim, Optimal Design of Experiments, Society for Industrial and Applied Mathematics, Philadelphia, Pa, USA, 1993.
J. Antony, Design of Experiments for Engineers and Scientists, Elsevier Science, 2003.
G. Taguchi and Y. Yokoyama, Taguchi Methods: Design of Experiments, ASI Press, 1993.
R. K. Roy, Design of Experiments Using the Taguchi Approach: 16 Steps to Product and Process Improvement, John Wiley & Sons, 2001.
X. Zhang, D. O. Hayward, and D. M. P. Mingos, “Effects of microwave dielectric heating on heterogeneous catalysis,” Catalysis Letters, vol. 88, no. 1-2, pp. 33–38, 2003.
View at: Publisher Site | Google Scholar
X. Zhang and D. O. Hayward, “Applications of microwave dielectric heating in environment-related heterogeneous gas-phase catalytic systems,” Inorganica Chimica Acta, vol. 359, no. 11, pp. 3421–3433, 2006.
View at: Publisher Site | Google Scholar
J. Xu, “Microwave irradiation and selectivities in organic reactions,” Progress in Chemistry, vol. 19, no. 5, pp. 700–712, 2007.
View at: Google Scholar
X. L. Li, Y. Q. Shan, D. B. Ye, Q. Z. Zhang, and X. H. Zheng, “Synthesis of β-(3, 4-Dihydroxyphenyl)-α-hydrox-N-[(R)-(3-phenyl-1-ethyloxyformyl) propyl] propanamide,” Chinese Journal of Synthetic Chemistry, vol. 16, no. 2, pp. 239–241, 2008.
View at: Google Scholar

Copyright

Copyright © 2013 Qun-Zheng Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies