International Journal of Organic Chemistry
Vol.08 No.04(2018), Article ID:88657,8 pages
10.4236/ijoc.2018.84026

Microwave Irradiated Cross Coupling of Carboxylic Acids and Crotyl Bromides: Efficient Application to Make Arachidonic Acid Esters

Mohammad Al-Masum*, Arpona Hira

Department of Chemistry, Tennessee State University, Nashville, USA

Copyright © 2018 by authors and Scientific Research Publishing Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).

http://creativecommons.org/licenses/by/4.0/

Received: September 20, 2018; Accepted: November 19, 2018; Published: November 22, 2018

ABSTRACT

A microwave irradiated palladium-catalyzed reaction of carboxylic acids and crotyl type bromides creates series of esters in good to high yields. This facile ester synthesis then is applied to make esters from arachidonic acid, salicylic acid, folic acid, and aspirin efficiently.

Keywords:

Arachidonic Acid Esters by Cross Coupling, Microwave

1. Introduction

Esters are common chemicals with extensive applications in medicine, biology, chemistry, and material sciences [1] - [7] . Esters used not only as solvents but also are in perfumes, essential oils, agriculture and food flavorings, antioxidant, plastics, detergents, and for many other purposes. Isoamyl acetate (odor of banana), ethyl butanoate (odor of mango), methyl 2-methylbutanoate (odor of pineapple), vitamin C, cocaine, etc., are some common interesting examples occurring in the nature. The enormous use of transition metal complexes to activate organic molecules makes them viable visions for developing catalytic processes with high selectivity and atom economy. This work focusses to find a facile way of making esters by microwave irradiated cross-coupling reaction of carboxylic acids, allyl type halides, in the presence of palladium-catalyst (Scheme 1) and apply that effective cross coupling method to synthesize arachidonic acid esters, and folic acid esters, etc.

2. Results and Discussion

Recently, PdCl2(dtbpf) complex has been successfully employed as a catalyst in

Scheme 1. Propionic acid ester from Propionic acid and alkyl halides.

various organic transformations involving potassium organotrifluoroborates [8] [9] [10] [11] [12] . The higher cone angle of P-Pd-P in PdCl2(dtbpf) may be improve its effectiveness as a catalyst. In order to see further application of this palladium complex, we thought to explore cross coupling reactions of carboxylic acids with 3-Bromo-1-phenyl-1-propene 2a and 1-bromo-2-butene 2b. We began our study with 3-bromo-1-phenyl-propene 2a and various carboxylic acids as substrates with the load of 3 mole % PdCl2(dtbpf). The reactions worked well when microwaved for 30 min. We turned our attention to optimization the reaction conditions and found 0.5 mole % catalyst works quite good with 3 h reaction time.

The results with 3-bromo-1-phenyl-1-propene 2a summarize in Figure 1. In case of cinnamic acid best result obtained with 3 mole % PdCl2(dtbpf) (Entry 10, Figure 1).

We also unzipped the cross coupling of carboxylic acids with 3-bromo-2-butene 2b. The reactions went very sluggish but with 3.0 mole % catalyst the desired products form in moderate yields. The results with 3-bromo-2-butene 2b summarize in Figure 2. In case of hexanoic acid and 2-octenoic acid, 0.5 mole % of catalyst worked well when treated with 1-bromo-2-butene 2b (Figure 2, Entries 2, 3).

It is a further object of the investigation to see the application of these methods and make the esters from arachidonic acid, folic acid, salicylic acids, etc. In fact, arachidonic acid, folic acid, salicylic acid, all form the corresponding esters when treated with halides 2a and 2b. Examples such as 4a, 4b, 4c, and 4d present in Scheme 2.

Our goal is to examine the significant biological effect of these new esters and report in due courses. Arachidonic and folic acid esters are useful biologically active compounds [13] [14] [15] [16] [17] . The probable catalytic cycle for this new transformation proposes in Scheme 3. This new method is eco-friendly, atom-economy, and sustainable green chemistry synthetic process. This new process will have potential value for complex ester synthesis.

3. Procedure

The synthesis of ester 3a from propionic acid 1a and 3-bromo-1-phenyl-1propene 2a is a representative one. A dry clean microwave vial was loaded with potassium carbonate (0.207 g, 1.5 mmol), PdCl2(dtbpf) (0.002 g, 0.0025 mmol), then capped the vial with septum and flushed with argon. After adding propionic acid (37.5 μL, 0.5 mmol), 3-bromo-1-phenyl-propene 2a (82.0 μL, 0.55 mmol) via micro syringe, and 1,4-dioxane (5.0 mL) in the microwave reaction vial, the resulting mixture was irradiated at 140˚C for 3 h. The crude reaction product filtered through sintered funnel and concentrate. For purification, the crude product passed through alumina using hexane/dichloromethane (100/1) as eluents. The purified product 3a obtained was 87% in yield (Figure 1, entry 1). Compound 3a, 1H NMR (CDCl3, 400 MHz) δ 7.24 (m, 5H), 6.57 (d, J = 15.8 Hz, 1H), 6.21 (dt, J = 6.44 Hz, 1H), 4.66 (d, J = 6.48 Hz, 2H), 2.30 (q, J = 7.56 Hz, 2H), 1.09 (t, J = 7.56 Hz, 3H); 13C NMR (CDCl3, 100 MHz)

Scheme 2. New esters from arachidonic, folic, and salicylic acids.

Figure 1. Esters from cross coupling of carboxylic acids and bromoalkenesa. aAll yields are isolated yields; bα-adduct is minor product; cMixture of E; and Z dCompound 3 j formed by adding 3 mole % PdCl2(dtbpf).

Figure 2. Esters from cross coupling of carboxylic acids and 3-bromo-2-butene2ba. aReactions run with the load of 3 mole % PdCl2(dtbpf); b3 l and 3 m products form with 0.5 mole % load of PdCl2(dtbpf).

Scheme 3. Catalytic cycle of esters from R1COOH and crotyl halide.

3.1. Figure 1

Compound 3a, 1H NMR (CDCl3, 400 MHz) δ 7.24 (m, 5H), 6.57 (d, J = 15.8 Hz, 1H), 6.21 (dt, J = 6.44 Hz, 1H), 4.66 (d, J = 6.48 Hz, 2H), 2.30 (q, J = 7.56 Hz, 2H), 1.09 (t, J = 7.56 Hz, 3H). 13C NMR (CDCl3, 100 MHz) δ 174.2, 136.2, 134.1, 128.6, 128.5, 128.0, 126.6, 123.3, 64.9, 27.6, 9.1;

Compound 3b, 1H NMR (CDCl3, 400 MHz) δ 7.25 (m, 5H,), 6.56 (d, J = 15.88 Hz, 1H), 6.20 (dt, J = 6.4 Hz, 1H), 4.65 (d, J = 6.4 Hz, 2H), 2.25 (t, J = 7.4 Hz, 2H), 1.61 (q, J = 7.4 Hz, 2H), 0.88 (t, J = 7.4 Hz, 3H). 13C NMR (CDCl3, 100 MHz) 173.3, 136.2, 134.9, 128.5, 127.9, 126.5, 123.3, 64.7, 36.1, 18.4, 13.6;

Compound 3c, 1H NMR (CDCl3, 400 MHz) δ 7.25 (m, 5H), 6.56 (d, J = 15.88 Hz, 1H), 6.20 (dt, J = 6.4 Hz, 1H), 4.65 (d, J = 6.4 Hz, 2H), 2.27 (t, J = 7.48 Hz, 2H), 1.58 (t, J = 7.4 Hz, 2H), 1.24 (m, 4H), 0.81 (m, 3H). 13C NMR (CDCl3, 100 MHz) δ 173.5, 136.2, 133.9, 128.5, 127.9, 126.5, 126.0, 123.3, 64.7, 34.2, 31.2, 24.6, 22.2, 13.8;

Compound 3d, 1H NMR (CDCl3, 400 MHz) δ 7.22 (m, 5H), 6.57 (d, J = 15.92 Hz, 1H), 6.20 (dt, J = 6.44 Hz, 1H), 5.48 (q, J = 5.36 Hz, 1H), 4.66 (d, J = 6.44 Hz, 1H), 2.99 (d, J = 5.4 Hz, 2H), 1.96 (m, 2H), 1.25 (m, 6H), 0.80 (t, J = 6.40 Hz, 3H). 13C NMR (CDCl3, 100 MHz) δ 173.9, 135.0, 134.1, 128.6, 126.6, 123.2, 121.3, 65.1, 38.1, 32.1, 31.3, 22.1, 13.9;

Compound 3e, 1H NMR (CDCl3, 400 MHz) δ 7.81 - 7.24 (m, 13H,), 6.35 (d, J = 15.88 Hz, 1H), 5.89 (dt, J = 6.4 Hz, 1H), 4.63 (d, J = 6.4 Hz, 2H). 13C NMR (CDCl3, 100 MHz) δ 168.4, 142.4, 141.3, 136.2, 133.8, 131.2, 130.6, 129.7, 128.4, 128.3, 128.0, 127.8, 127.1, 126.5, 122.5, 65.3;

Compound 3f, 1H NMR (CDCl3, 400 MHz) δ 7.49 - 7.31 (m, 8H), 6.81 (d, J = 15.88 Hz, 1H), 6.45 (dt, J = 6.44 Hz, 1H), 5.04 (dt, J = 6.44 Hz, 2H). 13C NMR (CDCl3, 100 MHz) δ 165.4, 136.2, 134.7, 132.6, 131.5, 128.6, 128.2, 126.7, 122.8, 66.1;

Compound 3g, 1H NMR (CDCl3, 400 MHz) δ 7.32 - 7.16 (m, 7H), 6.65 (d, J = 15.92 Hz, 1H), 6.29 (dt, J = 7.48 Hz, 1H), 4.87 (d, J = 6.36 Hz, 2H), 2.23 (s, 3H). 13C NMR (CDCl3, 100 MHz) δ 166.5, 143.7, 134.1, 129.7, 128.8, 128.6, 127.9, 126.6, 126.1, 123.4, 65.3, 21.7;

Compound 3h, 1H NMR (CDCl3, 400 MHz) δ 7.63 - 7.28 (m, 10H), 6.81 (d, J = 15.88 Hz, 1H), 6.46 (dt, J = 6.4 Hz, 1H), 5.04 (d, J = 6.4 Hz, 2H). 13C NMR (CDCl3, 100 MHz) δ 166.4, 134.3, 133.0, 129.7, 128.6, 128.4, 128.1, 127.9, 126.1, 123.3, 65.5;

Compound 3i, 1H NMR (CDCl3, 400 MHz) δ 7.49 - 7.01 (m, 9H), 6.63 (d, J = 15.88 Hz, 1H), 6.28 (m, 1H), 4.84 (d, J = 6.48, 2H). 13C NMR (CDCl3, 100 MHz) δ 169.1, 164.3, 150.6, 140.0, 134.6, 133.9, 131.9, 128.8, 128.6, 127.9, 126.6, 123.8, 122.8, 65.7, 21.0;

Compound 3j, 1H NMR (CDCl3, 400 MHz) δ 7.65 (d, J = 16.0 Hz, 1H), 7.34 - 7.15 (m, 10 H), 6.62 (d, J = 15.88 Hz, 1H), 6.40 (d, J = 16.0 Hz, 1H), 6.28 (dt, J = 6.48 Hz, 1H), 4.78 (d, J = 6.44 Hz, 2H); 13C NMR (Acetone-D6, 100 MHz) δ 171.0, 149.8, 141.6, 139.6, 138.2, 135.4, 134.0, 133.3, 131.6, 128.9, 123.1, 69.7.

3.2. Figure 2

Compound 3k, 1H NMR (CDCl3, 400 MHz) δ 5.46 (m, 1H), 5.27 (m, 1H), 4.16 (d, J = 6.4 Hz, 2H), 1.99 (q, J = 7.52 Hz, 2H), 1.40 (d, J = 6.52, 3H); 13C NMR (CDCl3, 100 MHz) δ 173.2, 130.1, 125.2, 64.3, 29.9, 26.8, 17.0, 8.49;

Compound 3l, 1H NMR (CDCl3, 400 MHz) δ 5.53 (m, 1H), 5.49 (m, 1H), 4.42 (d, J = 6.42 Hz, 2H), 2.23 (t, J = 7.64 Hz, 2H), 1.65 (d, J = 6.44 Hz, 3H), 1.55 (m, 2H), 1.23 (m, 4H), 0.82 (t, J = 6.8 Hz, 3H). 13C NMR (CDCl3, 100 MHz) δ 173. 5, 131.0, 125.1, 64.9, 34.2, 31.2, 22.2, 17.0, 13.7;

Compound 3m, 1H NMR (CDCl3, 400 MHz) δ 5.78 (m, 1H), 5.51 (m, 2H), 4.48 (d, J = 6.48 Hz, 1H), 3.00 (d, J = 5.44 Hz, 2H), 2.00 (m, 2H), 1.69 (m, 3H), 1.29 (m, 6H), 0.86 (t, J = 7.0, 3H). 13C NMR (CDCl3, 100 MHz) δ 172.0, 134.8, 131.3, 125.121.4, 65.2, 38.1, 32.1, 331.3, 22.1, 17.7, 13.8;

Compound 3n, 1H NMR (CDCl3, 400 MHz) δ 7.83 - 7.32 (m, 9H), 5.5 (m, 1H), 5.27 (m, 1H), 4.47 (d, J = 6.52, 2H), 1.08 (d, J = 6.48, 3H). 13C NMR (CDCl3, 100 MHz) δ 166.5, 142.4, 141.4, 137.3, 131.2, 130.6, 129.7, 128.5, 128.0, 127.1, 124.5, 60.5, 17.7;

Compound 3o, 1H NMR (CDCl3, 400 MHz) δ 7.75 - 7.18 (m, 4H), 5.80 (m, 1H), 5.63 (m, 1H), 4.69 (d, J = 6.4 Hz, 2H), 1.68 (d, J = 6.0 Hz, 3H). 13C NMR (CDCl3, 100 MHz) d 165.5, 137.3, 133.6, 132.4, 131.9, 131.0, 126.5, 124.7, 116.3, 66.2, 17.8;

Compound 3p, 1H NMR (CDCl3, 400 MHz) δ 7.91 (d, J = 8.2 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 5.58 (m, 1H), 5.68 (m, 1H), 4.71 (d, J = 6.36 Hz, 2H), 2.38 (s, 3H), 1.72 (d, J = 6.2 Hz, 3H), 0.80 (t, J = 6.0 Hz, 3H). 13C NMR (CDCl3, 100 MHz) δ 166.5, 143.5, 131.1, 129.6, 127.6, 125.2, 124.4, 65.4, 17.8;

Compound 3q, 1H NMR (CDCl3, 400 MHz) δ 8.02 - 7.49 (m, 5H), 5.89 (m, 1H), 5.73 (m, 1H), 4.74 (d, J = 6.32, 2H), 1.74 (d, J = 6.3 Hz, 3H). 13C NMR (CDCl3, 100 MHz) δ 162.1, 133.9, 131.7, 130.2, 126.4, 66.0, 17.9;

Compound 3r, 1H NMR (CDCl3, 400 MHz) δ 8.00 - 7.06 (m, 4H), 5.85 (m, 1H), 5.65 (m, 1H), 4.67 (d, J = 6.52 Hz, 2H), 2.30 (s, 3H), 1.72 (d, J = 6.52 Hz, 3H). 13C NMR (CDCl3, 100 MHz) δ 169.6, 164.3, 150.6, 133.7, 131.8, 125.9, 124.8, 123.7, 65.8, 21.0, 17.7;

Compound 3s, 1H NMR (CDCl3, 400 MHz) δ 7.70 - 7.42 (m, 5H, 1H), 6.55 (d, J = 16.06 Hz, 1H), 5.76 (m, 2H), 4.60 (d, J = 6.4 Hz, 2H), 1.7 (m, 3H);

Compound 4a, 1H NMR (CDCl3, 400 MHz) δ 7.23 (m, 5H), 6.56 (d, J = 13.4 Hz, 1H), 6.20 (dt, J = 6.44 Hz, 1H), 5.28 (m, 8H), 4.64 (d, J = 6.48 Hz, 2H), 2.72 (m, 6H), 2.29 (t, J = 7.6 Hz, 2H), 1.98 (m, 4H), 1.65 (t, J = 7.4 Hz, 2H), 1.20 (m, 6H), 0.80 (m, 3H);

Compound 4b, 1H NMR (CDCl3, 400 MHz) δ 5.72 (m, 1H), 5.56 (m, 1H), 5.35 (m, 8H), 4.47 (d, 6.5 Hz, 2H), 2.77 (m, 6H), 2.30 (m, 2H), 2.08 (m, 4H), 1.75 (m, 2H, 3H), 1.27 (m, 6H), 0.86 (m, 3H);

Compound 4c, major peak: 1H NMR (CDCl3, 400 MHz) δ 9.87 (s, 1H), 9.56 (s, 1H), 9.54 (s, 1H), 7.17 (m, aromatic), 6.5 - 6.25 (d, dt), 4.97 (m, 2H X 2).

Acknowledgements

ArponaHira gratefully acknowledges the graduate fellowship award from Tennessee State University, Nashville, TN. Authors thankfully acknowledge the NMR assistance from Dr. Donald F. Stec, Vanderbilt University, Nashville, TN.

Conflicts of Interest

The authors declare no conflicts of interest regarding the publication of this paper.

Cite this paper

Al-Masum, M. and Hira, A. (2018) Microwave Irradiated Cross Coupling of Carboxylic Acids and Crotyl Bromides: Efficient Application to Make Arachidonic Acid Esters. International Journal of Organic Chemistry, 8, 341-348. https://doi.org/10.4236/ijoc.2018.84026

References

  1. 1. Marshall, J.A. (2000) Synthesis and Reactions of Allylic, Allenic, Vinylic, and Arylmetal Reagents from Halides and Esters via Transient Organopalladium Intermediates. Chemical Reviews, 100, 3163-3185. https://doi.org/10.1021/cr000003u

  2. 2. Negishi, E., Huang, Z., Wang, G., Mohan, S., Wang, C. and Hattori, H. (2008) Recent Advances in Efficient and Selective Synthesis of Di-, Tri-, and Tetrasubstituted Alkenes via Pd-Catalyzed Alkenylation-Carbonyl Olefination Synergy. Accounts of Chemical Research, 41, 1474-1485. https://doi.org/10.1021/ar800038e

  3. 3. Okamoto, N., Miwa, Y., Minami, H., Takeda, K. and Yanada, R. (2011) Regio- and Stereoselective Multisubstituted Enol Ester Synthesis. The Journal of Organic Chemistry, 76, 9133-9138. https://doi.org/10.1021/ar800038e

  4. 4. Satchell, D.P.N. (1963) An Outline of Acylation. Quarterly Reviews, Chemical Society, 17, 160. https://doi.org/10.1039/qr9631700160

  5. 5. Eftekhari-Sis, B. and Zirak, M. (2017) α-Imino Esters in Organic Synthesis: Recent Advances. Chemical Reviews, 117, 8326-8419. https://doi.org/10.1021/acs.chemrev.7b00064

  6. 6. Inanaga, J., Kirata, K., Saeki, H., Katsuki, T. and Yamaguchi, M. (1979) A Rapis Esterification by Means of Mixed Anhydride and Its Application to Large-Ring Lactonization. Bulletin of the Chemical Society of Japan, 52, 1989-1993. https://doi.org/10.1246/bcsj.52.1989

  7. 7. Fischer, E. (1895) Darstellung der Ester. Berichte der Deutschen Chemischen Gesellschaft, 28, 3252-3258. https://doi.org/10.1002/cber.189502803176

  8. 8. Grasa, G.A. and Colacot, T.J. (2007) α-Arylation of Ketones Using Highly Active, Air-Stable (DtBPF)PdX2 (X = Cl, Br) Catalysts. Organic Letters, 9, 5489-5492.

  9. 9. Al-Masum, M., Saleh, N. and Islam, T. (2013) A Novel Route to Organonitrites by Pd-Catalyzed Cross-Coupling of Sodium Nitriteand Potassium Organotri-fluoroborates. Tetrahedron Letters, 54, 1141-1144.

  10. 10. Mann, G., Shelby, Q., Roy, A.H. and Hartwig, J.F. (2003) Electronic and Steric Effects on the Reductive Elimination of Diaryl Ethers from Palladium(II). Organometallics, 22, 2775-2789. https://doi.org/10.1021/om030230x

  11. 11. Elsagir, A.R., Gassner, F., Gorls, H. and Dinjus, E. (2000) Bidentate Ferrocenyl Phosphines and Their Palladium(II)Dichloride Complexes—X-Ray Structural and NMR Spectroscopic Investigations and First Results of Their Characteristics in the Pd-Catalyzed Oligomerization of 1,3-Butadiene with CO2. Journal of Organometallic Chemistry, 597, 139-145. https://doi.org/10.1016/S0022-328X(99)00670-1

  12. 12. Bianchini, C., Meli, A., Overhauser, W., Parisel, S., Passaglia, E., Ciardelli, F., Gusev, O.V., Kal’sin, A.M. and Vologdin, N.V. (2005) Ethylene Carbonylation in Methanol and in Aqueous Media by Palladium(II) Catalysts Modified with 1,1’- Bis(Dialkylphosphino)Ferrocenes. Organometallics, 24, 1018-1030. https://doi.org/10.1021/om049109w

  13. 13. Martin, S.A., Brash, A.R. and Murphy, R.C. (2016) The Discovery and Early Structural Studies of Arachidonic Acid. The Journal of Lipid Research, 57, 1126-1132. https://doi.org/10.1194/jlr.R068072

  14. 14. Li, D., Ng, A., Mann, N.J. and Sinclair, A.J. (1998) Contribution of Meat Fat to Dietary Arachidonic Acid. Lipids, 33, 437-440. https://doi.org/10.1007/s11745-998-0225-7

  15. 15. Tallima, H. and Rashika, E.R. (2018) Arachidonic Acid: Physiological Roles and Potential Health Benefits—A Review. Journal of Advanced Research, 4, 467-468. https://doi.org/10.1016/j.jare.2017.11.004

  16. 16. Groehn, V., Moser, R. and Pugin, B. (2005) Stereoselective Hydrogenation of Folic Acid Dimethyl Ester Benzenesulfonate: A New Access to Optically Pure l-Tetrahydrofolic Acid. Advanced Synthesis & Catalysis, 347, 1855-1862. https://doi.org/10.1002/adsc.200505098

  17. 17. Bailey, L.B. (1995) Folate in Health and Disease. Vol. 1, Marcel Dekker, Inc., New York, Basel, Hong Kong, 23-42.