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Article

Rapid Synthesis of Flavor Compound 4-Ethyloctanoic Acid under Microwave Irradiation

1
College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi’an 710021, China
2
School of Chemical and Environmental Engineering, Beijing Technology and Business University, Beijing 100048, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2010, 11(10), 4165-4174; https://doi.org/10.3390/ijms11104165
Submission received: 30 September 2010 / Revised: 20 October 2010 / Accepted: 21 October 2010 / Published: 25 October 2010
(This article belongs to the Section Green Chemistry)

Abstract

:
Rapid synthesis of 4-ethyloctanoic acid by means of microwave irradiation is described. Diethyl malonate reacted with 2-ethyl-1-bromohexane in the presence of sodium ethoxide to give diethyl (2-ethylhexyl)malonate (1b). 1b was saponified in the solution of ethanol and potassium hydroxide and then acidified to form (2-ethylhexyl)propanedioic acid (1c), and 1c was heated and decarboxylized to give 4-ethyloctanoic acid (1d). The influence of reaction temperature and reaction time on the yield of 1b and the effect of reaction time on the yield of 1c and 1d were investigated in order to optimize the synthetic conditions. The relative optimal conditions for the synthesis of 1b were a mole ratio of sodium to diethyl malonate to 2-ethylhexyl bromide of 0.1:0.11:0.11, a reaction temperature of 80–85 °C, and a reaction time of 2–2.5 h. The yield of 1b was about 79%. 1b was saponified for 30 min and then acidified to form 1c, and the yield of 1c was 96%. 1c was heated for 16 min at 180°C to give 1d, and the yield of 1d was about 90%. The overall yield of 1d is 70% under microwave irradiation. The reaction time was reduced greatly. In order to compare the result of microwave irradiation with that of an oil bath, the reactions were also performed in an oil bath. The structures of intermediates, product and by-product were confirmed by HRMS, 1H NMR, 13C-NMR and IR.

1. Introduction

4-Ethyloctanoic acid was first isolated from the root oil of the Costus plant (Saussurea lappa Clarke) by de Rijke [1]. In addition to costus root oil, 4-Ethyloctanoic acid also occurs in flue-cured virginia tobacco [2], aged Italian cheese [3], sheep cheese [4], goat cheese [5,6] and stewed beef gravy [7]. 4-Ethyloctanoic acid has waxy, fatty, creamy, moldy, sour sweaty, cheesy odor with animal-like nuances [8] and has been generally recognized as safe (GRAS) flavoring compounds (FEMA No. 3800) and as food additive in USA and China. It can be used for formulating food flavorings and added in meat products, soups, snack foods, milk products, hard candy, and chewing gum to improve their odors [9]. As raw material, 4-ethyloctanoic acid can be used for synthesizing new ester flavor compounds, such as 3-(methylthio)propyl-4-ethyloctanoate, 2-methyl-3-furanthiol-4-ethyloctanoate, 2-furanmethanethiol-4-ethyloctanoate, 4-methyl-5-thiazoleethanol-4-ethyloctanoate [10].
4-Ethyloctanoic acid can be synthesized by several methods. One method is that of S. G. Powell’s from 2-ethyl-1-bromohexane and diethyl malonate [11] (Scheme 1). This method offers the advantage of cheap and available materials with mild reaction conditions, but requires long reaction times [1215]. The British patent route by Knoevenagel reaction [16] (Scheme 2) offers a shorter reaction, but uses more expensive materials. The first step took 20 hours with a 50% yield of 2b; the second step required platinum oxide to conduct catalytic hydroprocessing under strict operational conditions with an overall yield of 4-ethyloctanoic acid of about 45%. A third method is the preparation of 4-ethyloctanoic acid by using cyano group activation [17] (Scheme 3); these starting materials are not readily available, but an overall yield of 4-ethyloctanoic acid was about 49%, so while this method may be used in small-scale laboratory syntheses and it is not suitable on a larger scale or in a manufacturing plant. The fourth method is the synthesis of 4-ethyloctanoic acid by coupling reaction [18] (Scheme 4). This method includes more steps and complex operational conditions. For example, the coupling reaction requires anhydrous conditions and low temperatures (−70 °C), so this method is only suitable for laboratory syntheses.
Microwave irradiation has attracted scientists’ attention as a powerful tool for rapid, green and efficient synthesis of a variety of compounds [19,20] including synthesis of some FEMA-GRAS approved flavoring agents [2124]. In view of the advantages and disadvantages of the four synthetic methods, we followed S. G. Powell’s method under microwave irradiation. The aim of the work was to optimize the reaction conditions of each step and supply useful data for a one pot reaction. We also investigated the degree of influence of microwave irradiation on the three chemical reactions. The reaction time was shortened greatly and demonstrating microwave irradiation had the most obvious effect on the alkylation reaction. The reaction conditions of the synthetic steps were optimized in this work.

2. Results and Discussion

2.1. The Optimization of Synthesis Conditions of Diethyl (2-Ethylhexyl)malonate (1b)

We investigated the influences of mole ratio of starting materials, reaction temperature and reaction time on the yield of 1b to optimize synthesis conditions. Different mole ratios of starting materials were used under the same operational conditions and the results are shown in Table 1. As the ratio of sodium to diethyl malonate increased, the yield of 1b decreased; as the ratio of 2-ethylhexyl bromide to diethyl malonate increased, the yield of 1b increased slightly. The reason was that excessive sodium increased the yield of by-product and decreased the yield of 1b. The by-product was separated by column chromatography and confirmed as diethyl di(2-ethylhexyl)malonate by spectrographic analysis. The by-product was formed by alkylation of 1b; excessive sodium resulted in the increase of the amount of sodium ethoxide, while sodium ethoxide deprotanated diethyl (2-ethylhexyl)malonate to form a carboanion, which subsequently reacted with 2-ethylhexyl bromide to yield the by-product, decreasing the yield of 1b. The optimal mole ratio of sodium to diethyl malonate to 2-ethylhexyl bromide was 0.1:0.11:0.11.
The effect of reaction temperature and reaction time on the yield of 1b under microwave irradiation was investigated. The reaction mixture was sampled and monitored via gas-chromatography at certain intervals. The main results are listed in Table 2. The results show that the higher the reaction temperature, the shorter the reaction time to reach the maximum concentration of 1b. When the reaction temperature rose from 75 °C to 80 °C, the yield of 1b increased from 73.3% to 79.1%; however, when the reaction temperature rose from 85 °C to 90 °C, the yield of 1b decreased from 78.2% to 72.8%. One possible reason is the occurrence of a side reaction. With the rise of reaction temperature, both the rates of the main reaction and the side reaction rate increased, but not to the same extent; this made the yield of 1b increase first and then decrease. Under microwave irradiation, the optimal reaction temperature was 80–85 °C, and the optimal reaction time was 2–2.5 h. As a comparison, the experiments were performed using an oil bath and the results are shown in Table 3. The results show that when using an oil bath, the reaction takes much more time to reach the higher yield.
The product 1b was analyzed by 13C-NMR. Because 1b is derived from diethyl malonate, there is a symmetric group in the structure of 1b, so there should be twelve signals visible in the 13C-NMR spectrum; however, there were eleven signals. A chemical shift of C8 was the same as that of CH3 from OCH2CH3, and the signal at 14.00 stood for two carbon atoms.

2.2. The Optimization of Reaction Time of Synthesis of (2-Ethylhexyl)propanedioic Acid (1c)

The reactions were carried out separately in an oil bath and under microwave irradiation in order to compare and optimize the reaction time for synthesis of 1c, and the results are listed in Table 4. The results indicated that the reaction took a shorter time to reach the higher yield under microwave irritation. The appropriate reaction time for synthesis of 1c under microwave irradiation was 30 min.
When 1c was dissolved in absolute ethanol and subjected to gas chromatography to measure the concentration of 1c, we found that 1c was decarboxylized to form 1d at 180 °C. The result suggested that the reaction temperature for preparing 1d from 1c would be 180 °C.

2.3. The Optimization of Reaction Time of Synthesis of 4-Ethyloctanoic Acid (1d)

Because 1c was decarboxylized to form 1d at 180 °C, it was not suitable to monitor the reaction via gas-chromatography; however, carbon dioxide is generated in the reaction, so the reaction procedure was monitored by measuring the reducing amount of reaction mixture. The reactions were performed separately using an oil bath and under microwave irradiation and the results are listed in Table 5.
The product obtained under microwave irradiation was slightly more than the product obtained using an oil bath, but there was little difference in reaction time, unlike the above reactions. The reason is that the polarity of 1c is weak and the reaction is not carried out in polar solvent to simplify the final treatment. The appropriate reaction time for synthesis of 1d under microwave irradiation was 16 min. After 1c was decarboxylized to form 1d, we found the chemical shift of carbon(CH) connected with carboxyl group changed from 49.80 to 38.27 in the 13C-NMR spectrums.
The total yields of 4-ethyloctanoic acid on oil bath and under microwave irradiation were calculated; they were 66% (78.9% × 96.1% × 87.0%) and 70% (79.1% × 97.7% × 90.6%). The reactions took more time when using an oil bath; the three steps needed separately 24 h, 150 min and 60 min. However, the three steps needed just 2.5 h, 30 min and 16 min under microwave irradiation.

3. Experimental Section

3.1. General

Sodium, anhydrous ethanol, diethyl malonate, potassium hydroxide, hydrochloric acid (36.5%), ethyl ether and sodium sulfate (anhydrous) were obtained from Sinopharm Chemical Reagent Beijing Co., Ltd. (Beijing, China). 2-Ethylhexyl bromide was obtained from Jiangsu WDL Chemical Co., Ltd. (Jiangsu, China).
The contents were determined on a Varian CP3800 gas chromatograph. High-resolution mass spectra were obtained at a Bruker Apex IV Fourier-Transform Mass Spectrometry in Peking University. 1H-NMR and 13C-NMR spectra were recorded on a Bruker DRX-300 nuclear magnetic resonance spectrometer. IR spectra were measured on a Nicolet Avater 370 Fourier transform infrared spectrometer. The reactor was a XH-300A xianghao microwave reactor.

3.2. Synthesis of Diethyl (2-Ethylhexyl)malonate (1b)

Sodium (2.3 g, 0.1 mol) was dissolved in 40 ml anhydrous ethanol and diethyl malonate (17.62 g, 0.11 mol) was added during agitation. While the resulting mixture was under microwave irradiation, 2-ethylhexyl bromide (21.24 g, 0.11 mol) was added dropwise over the course of 10 min then the reaction mixture was refluxed for 2.5 hours at 80 °C. At the end of reflux, ethanol in the reaction mixture was distilled off and the sample was washed with saturated NaCl aqueous solution. The organic layer was separated, and the aqueous layer was extracted with ethyl ether. The organic layer and the ethyl ether extraction were mixed together, washed with brine, dried with anhydrous NaSO4 and filtered to remove solids. After the ethyl ether was evaporated off in vacuo, the mixture was weighed, and the content of 1b in the mixture was determined by gas-chromatography. The product was further purified using distillation under the reduced pressure. B.p. 140 °C/0.8 KPa, HRMS (ESI+) m/z calcd. for C15H29O4 [M + H]+ 273.20604, found 273.20589, calcd. for C15H28O4Na [M + Na]+ 295.18798, found 295.18776. 1H NMR (300 MHz, CDCl3, δppm) 4.16–4.22 (m, 4H), 3.41 (t, 1H), 1.82–1.86 (m, 2H), 1.25–1.35 (m,15H), 0.83–0.90 (m, 6H). 13C-NMR (300 MHz, CDCl3, δ ppm) 169.72 (C=O), 61.15 (OCH2), 50.04 (CH), 36.71 (CH), 32.48 (CH2), 32.35 (CH2), 28.50 (CH2), 25.45 (CH2), 22.91 (CH2), 14.00 (2CH3), 10.37 (CH3). IR (KBr, cm−1) 2961, 2931, 2874, 1735, 1464, 1368, 1176, 1150, 1032.

3.3. The Isolation of By-Product (Diethyl Di(2-ethylhexyl)malonate) from the Distill Remainder of 1b

After the 1b was distilled off, the remaining sample was cooled and subjected to a column chromatographic separation using silica gel and 2% petroleum ether in ethyl acetate. The fractions collected were monitored by thin layer chromatography. The “best” fractions were mixed together, the petroleum ether and ethyl acetate were removed under the reduced pressure, and the purified by-product was obtained as a yellow and transparent liquid. HRMS(ESI+) m/z calcd. for C23H44O4Na [M + Na]+ 407.31318, found 407.31350. 1H-NMR (300 MHz, CDCl3, δ ppm) 4.09–4.16 (t, 2H), 1.87–1.89 (m, 2H), 1.19–1.26 (m, 12H), 0.77–0.89 (m, 6H); 13C-NMR (CDCl3, δ ppm) 172.79 (C=O), 60.84 (OCH2), 56.09 (CH), 36.62 (CH), 34.04 (CH2), 33.02 (CH2), 28.29 (CH2), 25.87 (CH2), 23.09 (CH2), 14.10 (CH3), 13.90 (CH3), 10.10 (CH3). IR (KBr, cm−1) 2958, 2929, 2874, 1731, 1464, 1179, 1380, 860, 727, 558.

3.4. Synthesis of (2-Ethylhexyl)propanedioic Acid (1c)

Diethyl (2-ethylhexyl)malonate (0.05 mol, 13.6 g) was added to a solution of KOH (11.2 g, 0.2 mol) in ethanol (40 mL 95%). Under microwave irradiation, the reaction mixture was refluxed for 0.5 hour, and then most of ethanol was distilled off and water (100 mL) was added. The resulting mixture was acidified with HCl (conc.) and the organic layer was separated. The water phase was extracted with ethyl ether. The organic phase and extracts were combined, washed with water and brine, dried with anhydrous NaSO4 and filtered to remove solids. After evaporation of the ethyl ether, 2-ethylhexylpropanedioic acid was obtained. M.p. 100.5–101.0 °C, HRMS (ESI+) m/z calcd. for C11H20O4Na [M + Na]+ 239.12538, found 239.12536. 1H NMR (300 MHz, CDCl3, δ ppm) 11.90 (s, 2H), 3.51–3.56 (t, 1H), 1.90 (m, 2H), 1.26–1.35 (m, 9H), 0.84–0.91 (m, 6H). 13C-NMR (300 MHz, CDCl3, δ ppm) 175.86 (COOH), 49.80 (CH), 36.64 (CH), 32.49 (CH2), 32.20 (CH2), 28.32 (CH2), 25.33 (CH2), 22.96 (CH2), 14.02 (CH3), 10.26 (CH3). IR (KBr, cm−1) 3435, 3006, 2916, 2859, 1604, 1525, 1394, 1374, 1270, 1129, 929.

3.5. Synthesis of 4-Ethyloctanoic Acid (1d)

Under microwave irradiation, (2-ethylhexyl)propanedioic acid (21.6 g, 0.1 mol) was heated for 16min at 180 °C. The resulting mixture was evaporated in vacuo to collect the distillate at 123 °C/0.5 KPa and obtain 4-ethyloctanoic acid. HRMS (ESI+) m/z calcd. for C10H19O2 [M – H]+ 171.13905, found 171.13894. 1H NMR (300 MHz, CDCl3, δppm) 11.67 (s, 1H), 2.30–2.36 (m, 2H), 1.60–1.62 (m, 2H), 1.25–1.31 (m, 9H), 0.87–0.91 (m, 6H). 13C-NMR (300 MHz, CDCl3, δppm) 181.05 (COOH), 38.27 (CH), 32.39 (CH2), 31.60 (CH2), 28.72 (CH2), 27.92 (CH2), 25.48 (CH2), 23.04 (CH2), 14.07 (CH3), 10.65 (CH3). IR (KBr, cm−1) 3300-2500, 2960, 2929, 2873, 1711, 1459, 1413, 1380, 1292, 935.

4. Conclusions

4-Ethyloctanoic acid was synthesized starting from diethyl malonate through alkylation, saponification, acidification and decarboxylation under microwave irradiation. The reaction of diethyl malonate with 2-ethylhexyl bromide gave diethyl (2-ethylhexyl)malonate in about 79% yield. Diethyl (2-ethylhexyl)malonate was saponified and acidified to form (2-ethylhexyl)propanedioic acid in about 96% yield. (2-Ethylhexyl)propanedioic acid was heated and decarboxylized to give 4-ethyloctanoic acid in about 90% yield. The overall yield of 4-ethyloctanoic acid is 70%. This method provides a simple, rapid and eco-friendly synthesis of 4-ethyloctanoic acid.

Acknowledgements

The project was supported by Beijing Municipal Party Committee Organization Department (No: 20081D0500300127).

References

  1. Rijke, DD; Traas, PC; Heide, RT. Acidic components in essential oils of costus root, patchouli and olibanum. Phytochemistry 1978, 17, 1664–1666. [Google Scholar]
  2. Anderson, RC; Kelly, AG. Identification of a low flavor threshold carboxylic acid constituent, 4-ethyloctanoic acid, in flue-cured Virginia tobacco. J. Agric. Food Chem 1988, 36, 353–354. [Google Scholar]
  3. Ha, JK; Lindsay, RC. Volatile branched-chain fatty acids and phenolic compounds in aged Italian cheesw flavors. J. Food Sci 1991, 56, 1241–1247. [Google Scholar]
  4. Ha, JK; Lindsay, RC. Contribution of cow, sheep, and goat milks to characterizing branchedchain fatty acid and phenolic flavors in varietal cheeses. J. Dairy Sci 1991, 74, 3267–3274. [Google Scholar]
  5. Salles, C; Sommerer, N; Septier, C. Goat cheese flavor: Sensory evaluation of branched-chain fatty acids and small peptides. J. Food Sci 2002, 67, 835–841. [Google Scholar]
  6. Carunchia-Whetstine, ME; Karagul-Yuceer, Y; Avsar, YK. Identification andquantification of character aroma components in fresh chevre-style goat cheese. J. Food Sci 2003, 68, 2441–2447. [Google Scholar]
  7. Christlbauer, M; Schieberle, P. Characterization of the key aroma compounds in beef and pork vegetable gravies á la chef by application of the aroma extract dilution analysis. J. Agric. Food Chem 2009, 57, 9114–9122. [Google Scholar]
  8. Mosciano, G. Organoleptic characteristics of flavor materials. Perfum. Flavor 2007, 32, 16–18. [Google Scholar]
  9. Oser, BL; Ford, RA. GRAS flavoring Substances 17. Food Tech 1996, 50, 78–80. [Google Scholar]
  10. Liu, Y; Chen, H; Yin, D; Sun, B. Synthesis and odor evaluation of five new sulfur-containing ester flavor compounds from 4-ethyloctanoic acid. Molecules 2010, 15, 5104–5111. [Google Scholar]
  11. Powell, SG; Baldwin, MM. The condensation of 2-butanone with aldehydes of the type RR1CHCHO. J. Am. Chem. Soc 1936, 58, 1871–1872. [Google Scholar]
  12. Keil, W. The fat from fatty acids with odd numbers of carbon atoms. III. Z. Physiol. Chem 1942, 274, 175–185. [Google Scholar]
  13. Petrov, AD; Nikishin, GI; Ogibin, YN. The synthesis and surface-active properties of branched chain acids of the series, CnH2n+1COOH, with a C chain, C10–C20. Vses. Nauchn.-Issled. Inst. Zhirov 1960, 20, 278–292. [Google Scholar]
  14. Dziomko, VM; Dunaevskaya, KA. Synthesis of some aliphatic ketones with branched chains and different distance of branches from oxo group. Tr. Vses. Nauch. Issled. Inst 1966, 28, 184–192. [Google Scholar]
  15. Hedenstrom, E; Nguyen, BV; Silks, LA. Do enzymes recognize remotely located stereocentres? Highly enantioselective Candida rugosa lipase-catalysed esterification of the 2- to 8-methyldecanoic acids. Tetrahedron Asymmetry 2002, 13, 835–844. [Google Scholar]
  16. Neth, NV. Naarden International. Branched-chain carboxylic acids as perfume components. GB Patent 1,503,241, 8 March 1978. [Google Scholar]
  17. Larcheveque, M; Cuvigny, T. A new preparation of β and γ-alkyl aldehydes or acids by using activating cyano group. Tetrahedron Lett 1975, 44, 3851–3854. [Google Scholar]
  18. Sugiyama, T; Sasada, H; Masaki, J; Yamashita, K. Unusual fatty acids with specific odor from mature male goat. Agric. Boil. Chem 1981, 45, 2655–2658. [Google Scholar]
  19. Srivastava, KP; Mishra, PK. Green syntheses of 4-substitued-3-phenyl sydnones under microwave irradiation. Int. J. Pure Appl. Chem 2008, 3, 171–174. [Google Scholar]
  20. Reyes, L; Corona, S; Arroyo, G. Eco-contribution for the production of N-arylnitrones: Solventfree and assisted by microwaves. Int. J. Mol. Sci 2010, 11, 2576–2583. [Google Scholar]
  21. Sinha, AK; Sharma, A; Joshi, BP. One-pot two-step synthesis of 4-vinylphenols from 4-hydroxy substituted benzaldehydes under microwave irradiation: A new perspective on the classical Knoevenagel-Doebner reaction. Tetrahedron 2007, 63, 960–965. [Google Scholar]
  22. Nomura, E; Hosoda, A; Mori, H; Taniguchi, H. Rapid base-catalyzed decarboxylation and amide-forming reaction of substituted cinnamic acids via microwave heating. Green Chem 2005, 7, 863–866. [Google Scholar]
  23. Sharma, A; Kumar, R; Sharma, N; Sinha, AK. Unique versatility of ionic liquids as clean decarboxylation catalyst cum solvent: A metal- and quinoline-free paradigm towards synthesis of indoles, styrenes, stilbenes and arene derivatives under microwave irradiation in aqueous conditions. Adv. Synth. Catal 2008, 350, 2910–2920. [Google Scholar]
  24. Sinha, AK; Joshi, BP; Sharma, A. Microwave induced process for the preparation of substituted 4-vinylphenols. US Patent 6,989,467, 24 January 2006. [Google Scholar]
Scheme 1. S. G. Powell’s method.
Scheme 1. S. G. Powell’s method.
Ijms 11 04165f1
Scheme 2. British patent route.
Scheme 2. British patent route.
Ijms 11 04165f2
Scheme 3. Synthesis by cyano group activation.
Scheme 3. Synthesis by cyano group activation.
Ijms 11 04165f3
Scheme 4. Synthesis by coupling reaction.
Scheme 4. Synthesis by coupling reaction.
Ijms 11 04165f4
Table 1. Influence of different mole ratio of materials on the yield.
Table 1. Influence of different mole ratio of materials on the yield.
Runn (sodium)n(diethyl malonate)n(2-ethylhexyl bromide)Yield of 1b (%)
10.1050.1050.178.1
20.1100.1050.170.6
30.1100.1100.177.3
40.1150.1100.173.4
50.10.1050.10576.1
60.10.1050.11076.6
70.10.1100.11078.7
80.10.1100.11578.8
Reaction conditions: reaction temperature, 80 °C; reaction time, 24 h [12]; heating method, oil bath.
Table 2. Effect of reaction temperature and reaction time on the yield.
Table 2. Effect of reaction temperature and reaction time on the yield.
Reaction temperature (°C)Maximum concentration of 1b in reaction mixture (%)Reaction time (h)Yield of 1b (%)
7570.923.073.3
8076.372.579.1
8574.222.078.2
9070.531.572.8
Reaction conditions: the mole ratio of sodium, diethyl malonate to 2-ethylhexyl bromide, 0.1:0.11:0.11; heating method, microwave irradiation.
Table 3. Effect of reaction time on the yield of 1b in an oil bath.
Table 3. Effect of reaction time on the yield of 1b in an oil bath.
Reaction time (h)6121824
Yield of 1b (%)71.075.577.278.9
Reaction conditions: the mole ratio of sodium, diethyl malonate to 2-ethylhexyl bromide, 0.1:0.11:0.11; heating method, oil bath; reaction temperature, 80 °C.
Table 4. Effect of reaction time on the yield of 1c.
Table 4. Effect of reaction time on the yield of 1c.
In oil bathUnder microwave irradiation

Reaction time (min)Yield of 1c (%)Reaction time (min)Yield of 1c (%)
6093.0594.3
9095.51096.1
12095.92097.4
15096.13097.7
Reaction conditions: the mole ratio of potassium hydroxide to diethyl 2-ethylhexyl-malonate (1b), 0.4:0.1; 1b, 0.05 mol; reaction temperature, 85 °C.
Table 5. Effect of reaction time on the reaction.
Table 5. Effect of reaction time on the reaction.
In oil bathUnder microwave irradiation

Reaction time (min)The reducing amount of reaction mixture (g)Reaction time min)The reducing amount of reaction mixture (g)
54.18644.679
154.44584.719
304.536124.746
604.575164.759

Separated yield of 1d(%)87.0Separated yield of 1d(%)90.6
Reaction conditions: reaction temperature, 180 °C; 1c, 0.1 mol (21.6 g).

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MDPI and ACS Style

Liu, Y.-P.; Yin, D.-C.; Chen, H.-T.; Sun, B.-G. Rapid Synthesis of Flavor Compound 4-Ethyloctanoic Acid under Microwave Irradiation. Int. J. Mol. Sci. 2010, 11, 4165-4174. https://doi.org/10.3390/ijms11104165

AMA Style

Liu Y-P, Yin D-C, Chen H-T, Sun B-G. Rapid Synthesis of Flavor Compound 4-Ethyloctanoic Acid under Microwave Irradiation. International Journal of Molecular Sciences. 2010; 11(10):4165-4174. https://doi.org/10.3390/ijms11104165

Chicago/Turabian Style

Liu, Yu-Ping, De-Cai Yin, Hai-Tao Chen, and Bao-Guo Sun. 2010. "Rapid Synthesis of Flavor Compound 4-Ethyloctanoic Acid under Microwave Irradiation" International Journal of Molecular Sciences 11, no. 10: 4165-4174. https://doi.org/10.3390/ijms11104165

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