New Strategy for the Synthesis of Morpholine Cores: Synthesis from N-Propargylamines

Document Type : Review Article

Authors

1 Department of Chemistry, Payame Noor University, Tehran, I.R. IRAN

2 Department of Engineering Science, College of Engineering, University of Tehran, P.O. Box 11365-4563 Tehran, I.R. IRAN

3 Department of Chemistry, Tabriz Branch, Islamic Azad University, Tabriz, I.R. IRAN

Abstract

Functionalized morpholines have attracted much attention due to their potential biological activities. Despite the wide importance of morpholine derivatives in drug design of various pharmacological agents, the development of new approaches to their synthesis remains relatively unexplored. Given the low cost and easy availability of N-propargylamines, the synthesis of functionalized morpholines from these versatile building blocks have undergone an explosive growth in recent years. This review provides a concise overview of the synthesis of morpholine cores from N-propargyalamines in recent years.
 

Keywords

Main Subjects


[1] (a) Anaraki-Ardakani H., Nekomanesh P., Synthesis of Polyfunctionalized Pyrroles by a PPh3-Promoted Condensation Reaction between Ammonium Acetate, Dialkyl Acetylenedicarboxylate and Arylglyoxals, Iran. J. Chem. Chem. Eng. (IJCCE), (2017) in press.
(b) Behmadi H., Moghaddam Z. A., Poormorteza N., Beyramabadi S.A., Nezhad M.A., A four Components, One-Pot Synthesis of New Imidazole Molecular Tweezers Based on 2,4,6-Triarylpyridine as Hinge Region, Iran. J. Chem. Chem. Eng. (IJCCE), 36(1): 11-17 (2017).;
(c) Hasaninejad A., Zare A., Zolfigol M.A., Abdeshah M., Ghaderi A., Nami-Ana F., Synthesis of Poly-Substituted Quinolines via Friedländer Hetero-Annulation Reaction Using Silica-Supported P2O5 under Solvent-Free Conditions, Iran. J. Chem. Chem. Eng. (IJCCE), 30(1): 73-81 (2011).;
(d) Beyzaei H., Beygi A., Aryan R., One-Pot Ynthesis and Characterization of Highly Functionalized Thiazoles, Iran. J. Chem. Chem. Eng. (IJCCE), 35(4): 31-37 (2016).;
(e) Aboudi J., Bayat Y., Abedi Y., Nabati M., Mahkam M., 3-Nitro, 1-Amino Guanidine and 5-Hydrazino-1H-Tetrazole Derivatives as New Energetic Materials, Iran. J. Chem. Chem. Eng. (IJCCE), 34(2): 1-16 (2015).
[2] (a) Somei M., Aoki K., Nagahama Y., Nakagawa K., Simple Synthesis of Marine Alkaloid, (±)-Chelonin A, and Its Analogs, Heterocycles., 41(1): 5-8 (1995).;
(b) Guzii A.G., Makarieva T.N., Denisenko V.A., Dmitrenok P.S., Kuzmich A.S., Dyshlovoy S.A., Krasokhin V.B., Stonik V.A., Monanchocidin:
A New Apoptosis-Inducing Polycyclic Guanidine Alkaloid from the Marine Sponge Monanchora pulchra, Org. Lett., 12(19): 4292-4295 (2010).
(c) Tong X.G., Zhou L.L., Wang Y.H., Xia C., Wang Y., Liang M, Hou F.F., Cheng Y.X., Acortatarins A and B, Two novel Antioxidative Spiroalkaloids with  a Naturally unusual Morpholine Motif from Acorus Tatarinowii, Org. Lett., 12(8): 1844-1847 (2010).
[3] Weigelt J., Itani K., Stevens D., Lau W., Dryden M., Knirsch C., Group L.C.S., Linezolid Versus Vancomycin in Treatment of Complicated Skin and Soft Tissue Infections, Antimicrob. Agents. Chemother., 49(6): 2260-2266 (2005).
[4] McKeage K., Finafloxacin: First Global Approval, Drugs., 75(6): 687-693 (2015).
[5] Hesketh PJ., Grunberg S.M., Gralla R.J., Warr D.G., Roila F., De Wit R., Chawla S.P., Carides A.D., Ianus J., Elmer M.E., The Oral Neurokinin-1 Antagonist Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial in Patients Receiving High-Dose Cisplatin—The Aprepitant Protocol 052 Study Group, J. Clin. Oncol., 21(22): 4112-4119 (2003).
[6] Hajós M., Fleishaker J.C., Filipiak‐Reisner J.K., Brown M.T., Wong E.H., The Selective Norepinephrine Reuptake Inhibitor Antidepressant Reboxetine: Pharmacological and Clinical Profile, CNS. Drug. Rev., 10(1): 23-44 (2004).
[7] Asif M., Overview on Emorfazone and Other Related 3(2H)pyridazinone Analogues Displaying Analgesic and Anti-Inflammatory Activity, Ann. Med. Chem. Res., 1(1): 1-9 (2015).
[8] Yao L.F., Wang Y., Huang K.W., Synthesis of Morpholine or Piperazine Derivatives Through Gold-Catalyzed Cyclization Reactions of Alkynylamines or Alkynylalcohols, Org. Chem. Front., 2(6): 721-725 (2015).
[9] Vessally E., A New Avenue to the Synthesis of Highly Substituted Pyrroles: Synthesis from N-Propargylamines, RSC Adv., 6(22): 18619-18631 (2016).
[10] Vessally E., Hosseinian A., Edjlali L., Bekhradnia A., Esrafili M.D., New Page to Access Pyridine Derivatives: Synthesis from N-Propargylamines, RSC Adv., 6(75): 71662-71675 (2016).
[11] Vessally E., Hosseinian A., Edjlali L., Bekhradnia A., Esrafili M.D., New Page to Access Pyrazines and their Ring Fused Analogues: Synthesis from N-Propargylamines, Curr. Org. Synth., 14(4): 557-567 (2017).
[12] Vessally E., Edjlali L., Hosseinian A., Bekhradnia A., Esrafili M.D., Novel Routes to Quinoline Derivatives from N-Propargylamines, RSC Adv., 6(55): 49730-49746 (2016).
[13] Vessally E., Amiri S.S., Hosseinian A., Edjlali L., New Protocols to Access Imidazoles and Their Ring Fused Analogues: Synthesis from N-Propargylamines, RSC Adv., 7(12): 7079-7091 (2017).
[14] Vessally E., Hosseinian A., Edjlali L., Bekhradnia A., Esrafili M.D., New Route to 1,4-Oxazepane and 1,4-Diazepane Derivatives: Synthesis from N-Propargylamines, RSC Adv., 6(102): 99781-99793 (2016).
[15] Arshadi S., Vessally E.,  Edjlali L., Ghorbani-kalhor E., Hosseinzadeh-Khanmir R., N-propargylic β-Enaminocarbonyls: A Powerful and Versatile Building Block in Organic Synthesis., RSC Adv., 7(22): 13198-13211 (2017).
[16] Arshadi S., Vessally E., Edjlali L., Hosseinzadeh-Khanmir R., Ghorbani-kalhor E., N-Propargylamines: Versatile Building Blocks in the Construction of Thiazole Cores., Beilstein. J. Org. Chem. 13: 625-638 (2017).
[17] (a) Jiang B., Xu M., Highly Enantioselective Construction of Fused Pyrrolidine Systems that Contain a Quaternary Sereocenter: Concise Formal Synthesis of (+)-Conessine, Angew. Chem. Int. Ed., 43(19): 2543-2546 (2004).;
(b) Fleming J.J., Du Bois J., A Synthesis of (+)-Saxitoxin, J. Am. Chem. Soc., 128(12): 3926-3927 (2006).
[18] Yamamoto M., Tanaka S., Naruchi K., Yamada K., A Novel Synthesis of 2,3-Dihydro-4H-1,4-Oxazin-2-Ones and 6-mMethylene-2-Morpholinones, Synthesis., (10): 850-852 (1982).
[19] Mock J.N., Taliaferro J.P., Lu X., Patel S.K., Cummings B.S., Long T.E., Haloenol Pyranones and Morpholinones as Antineoplastic Agents of Prostate Cancer, Bioorg. Med. Chem. Lett., 22(14): 4854-4858 (2012).
[20] Dai L.Z., Qi M.J., Shi Y.L., Liu X.G., Shi M., Gold(I)-Catalyzed Cascade Cyclization Reaction: Highly Regio- and Diastereoselective Intermolecular Addition of Water and Alcohols to Epoxy Alkynes, Org. Lett., 9(16): 3191-3194 (2007).
[21] Wang Z., Lin X., Luck R.L., Gibbons G., Fang S., Synthesis of Cyclic Allyl Vinyl Ethers Using Pt(II)-Catalyzed Isomerization of Oxo-Alkynes, Tetrahedron., 65(13): 2643-2648 (2009).
[22] Vandavasi J.K., Hu W.P., Chen H.Y., Senadi G.C., Chen C.Y., Wang J.J., A New Approach to 1,4-Oxazines and 1,4-Oxazepines via Base-Promoted Exo Mode Cyclization of Alkynyl Alcohols: Mechanism and DFT Studies, Org. Lett., 14(12): 3134-3137 (2012).
[23] Yamamoto M., Cyclisation of Phenol- and Enol-Acetylenes : Syntheses of 2,3-Dihydro-2-Methylene-l,4-Benzodioxins and -1.4-Benzoxazines, J. Chem. Soc., Perkin Trans. 1., 3161-3165 (1979).
[24] Chaudhuri G., Chowdhury C., Kundu, N.G., A Highly Stereoselective Synthesis of (Z)-N-Aryl(alkyl)-2-Arylidine-2,3-Dihydro-1,4-Benzoxazines Through Palladium Catalyzed Reactions, Synlett., (11): 1273-1275 (1998).
[25] Kundu N.G., Chaudhuri G., Upadhyay A., Palladium-Catalyzed Heteroannulation Leading to Heterocyclic Structures with Two Heteroatoms: A Highly Regio- and Stereoselective Synthesis of (Z)-4-Alkyl-2-Alkyl(Aryl)Idene-3,4-Dihydro-2H-1, 4-Benzoxazines and (Z)-3-Alkyl(Aryl)Idene-4-Tosyl-3,4-Dihydro-2H-1,4-Benzoxazines, J. Org. Chem., 66(1): 20-29 (2001).
[26] Manzo A.M., Perboni A., Broggini G., Rigamonti M., An Alternative Synthesis of 2-Alkylidene-3,4-Dihydro-2H-1,4-Benzoxazines by Intramolecular Gold-Catalyzed Hydroalkoxylation of 2-(Prop-2-yn-1-Ylamino)Phenols, Synthesis., (1): 127-132 (2011).
[27] Lee D., Park S., Yu Y., Synthesis of 2-(Arylmethylene)-1,4-Benzoxazin-3-One by One-Pot Sonogashira and 6-exo-dig Cyclization, Heterocycles., 91(8): 1660-1667 (2015).
[28] Taskaya S., Menges N., Balci M., Gold-Catalyzed Formation of Pyrrolo- and Indolo-Oxazin-1-One Derivatives: The Key Structure of Some Marine Natural Products, Beilstein J. Org. Chem., 11, 897-905 (2015).
[29] Dai L.Z., Shi M., A Gold(I)-Catalyzed Intramolecular Reaction of Propargylic/homopropargylic Alcohols with Oxirane, Chem. Eur. J., 14(23): 7011-7018 (2008).
[30] Diéguez‐Vázquez A., Tzschucke C.C., Lam W.Y., Ley S.V., PtCl4-Catalyzed Domino Synthesis of Fused Bicyclic Acetals, Angew. Chem. Int. Ed., 47(1): 209-212 (2008).
[31] Barluenga J., Fernández A., Diéguez A., Rodríguez F., Fañanás F.J., Gold- or Platinum-Catalyzed Cascade Processes of Alkynol Derivatives Involving Hydroalkoxylation Reactions Followed by Prins-Type Cyclizations, Chem. Eur. J., 15(43): 11660-11667 (2009).
[32] Alcaide B., Almendros P., Carrascosa R., Torres M.R., Gold/Acid-Cocatalyzed Regiodivergent Preparation of Bridged Ketals via Direct Bis-Oxycyclization of Alkynic Acetonides, Adv. Synth. Catal., 352(8): 1277-1283 (2010).
[33] Alcaide B., Almendros P., Carrascosa R., Gold-Catalyzed Direct Cycloketalization of Acetonide-Tethered Alkynes in the Presence of Water, Tetrahedron., 68(46): 9391-9396 (2012).