SYNTHESIS OF PICHROMENES 1 DERIVATIVES

VIETNAM NATIONAL UNIVERSITY, HA NOI VNU UNIVERSITY OF SCIENCE FACULTY OF CHEMISTRY Nguyen Thanh Binh SYNTHESIS OF PICHROMENES DERIVATIVES Submitted in partial fulfillment of the requirements for the degree of Bachelor of Science in Chemistry (Advanced Program) Ha Noi - 2013 VIETNAM NATIONAL UNIVERSITY, HA NOI VNU UNIVERSITY OF SCIENCE FACULTY OF CHEMISTRY Nguyen Thanh Binh SYNTHESIS OF PICHROMENES DERIVATIVES Submitted in partial fulfillment of the requirements for the degree of Bachelor of Science in Chemistry (Advanced Program) Supervisor: Dr Mac Dinh Hung Assoc Prof.Dr.Dr Luu Van Boi Ha Noi - 2013 ACKNOWLEDGMENTS I would like to express a deep gratitude to my supervisor, Professor Luu Van Boi for his generous support about materials over the past four years despite of his heavy positions in many big projects I want to specially thank to my fantastic mentor, Dr Mac Dinh Hung for his patient guidance and enthusiasm to help me directly in every step in this project He is really a mirror for me to learn both knowledge and experiences at laboratory He has taught me many valuable techniques which under his observation I was getting better day by day I also want to express my continuing appreciation to entire Organic Synthetic Laboratory III for sharing and exchanging chemicals and apparatus no matter how insufficient I know our conditions are Lastly, I am grateful to my family and friends for being there all the time with love and support no matter how downcast I am with the failure of reactions I carried out Hanoi, May 14th, 2013 Nguyen Thanh Binh Contents INTRODUCTION Chapter : OVERVIEW 1.1 Application methods to synthesize nitro- chromene derivatives 1.1.1 Condensation between salicyaldehyde and α,β unsaturated compounds using organocatalysts 1.1.2 Ring-closing metathesis for the synthesis of Chromene 10 1.1.3 Microwave assisted synthesis of 3- Nitro-2H-chromene under solventless phase transfer catalytic conditions 10 1.2.Carboxylate chromene derivatives synthesis screening 11 1.3 Biological activities of chromene derivatives 13 Chapter - RESULT AND DISCUSSION 18 2.1.1.Application to synthesize 3-nitro-2-phenyl-2H-chromene ‘s derivatives 19 2.1.2 Spectroscopic data of 3-nitro-2-phenyl-2H-chromene derivatives 19 2.1.3 Proposed mechanism for the condensation of salicyaldehyde and βnitrostyrene 20 2.1.4 Synthesis of some derivatives of 3-nitro-2-phenyl-2H-chromene 20 2.2.1 Synthesis of 2-phenyl-2H-chromene carboxylate derivatives 25 Chapter : EXPERIMENTS 28 3.1 Chemicals 29 3.2 Instruments 29 3.3 Experiments 29 3.3.1Synthesis of 3-nitro-2-phenyl-2H-chromene derivative 29 3.3.2 Synthesis of ethyl cinnamate 33 3.3.3.Synthesis of methyl 3-(4-fluorophenyl) acrylate 33 3.3.4 Synthesis of carboxylate chromenes derivative 34 CONCLUSION 35 REFERENCES 36 APPENDIX 38 ABBREVIATION DABCO : 1,4 –diazabicyclo [ 2,2,2] octane DBU : 1,8 – Diazabicycloundec-7-ene DCM : dichlomethane DMF : dimethylformamide DMSO : dimethyl sulfoxide NMR : nuclear magnetic resonance TBAB : tetrabutylammonium bromide TLC : thin layer chromatography TMG : 1,1,3,3-tetramethyl guadinine LIST OF FIGURES Figure : Pichromene Figure : Compounds with 2H-Chromene skeleton Figure : Structure of 2H-chromene isolated from Sargassum micracanthum 14 Figure : Nitro-chromene skeleton 18 Figure 5: Ester chromene skeleton 19 Figure : 1HNMR of 8-ethoxy-3-nitro-2-(3,4,5-trimethoxyphenyl)-2H-chromene 22 Figure 7:13C-NMR of 8-ethoxy-3-nitro-(3,4,5-trimethoxyphenyl)-2H-chromene 23 Figure 8:1H-NMR of ethyl cinnamate 26 Figure 9:1H-NMR of methyl 3-(4-fluorophenyl) acrylate 27 LIST OF TABLES Table : Condensation products between salicyaldehydes and α,β-nitrostyrene 22 Table 2: 1H-NMR and 13C-NMR data of 3-nitro-2-phenyl-2H-chromene derivatives 24 Table 3: Condensation of salicyaldehydes and cinnamates 28 LIST OF SCHEMES Scheme : Syntheis of 3-nitro-2-phenyl-2H-chromene reported by Sakakibara Scheme : Synthesis of 2-H chromene derivatives using catalysts Scheme 3: Synthesis of 2-H Chromene using DABCO as catalyst 10 Scheme 4: Ring-closing metathesis for the synthesis of Chromene 10 Scheme 5: Synthesis of 3-nitrochromene derivative using microwave assistance 11 Scheme 6: Synthesis of chromene starting under the condition of K2CO3 11 Scheme 7: Synthesis of Chromene under the condition of K2CO3 and DMSO 12 Scheme 8: General synthesis of Chromene reported by Cheng 12 Scheme 9: Synthesis of Chromene esters 13 Scheme 10: Synthesis of salicyaldehyde with tert-butyl acrylate 13 Scheme 11: General procedure to synthesize 3-nitro-2-phenyl-2H-chromene 21 scheme 12: Synthesis of ester chromene 25 scheme 13: Esterification between cinnamic acid and ethanol 25 INTRODUCTION 2H- chromene ( 2H-1 benzopyran) is a compound which resulted from the fusion of a benzene ring to a heterocyclic pyran ring 2H-chromenes and its derivatives have been found in many biologically active natural products that possess variety of activities including as anti-tumorous, antibacterial, antiviral, anti-oxidative agents Among of those derivatives from 2H-chromene, pichromene (Figure 1) has been used as a treatment in blood cancer therapy due to its ability to prevent tumorous cells from growing by inhibiting the expression of D1, D2 and D3 as well as inducing apoptosis in leukemia and myeloma cells Figure : Pichromene Aforementioned, pichromene and its derivatives are of considerable current interest for a chemotherapy in blood cancer treatment In Vietnam, not many reports found to learn about those promising biological compounds so this thesis is a compilation of methods that are commonly used to apply for synthesis of pichromene’s derivatives in effective and simple ways The study was carried out at Medicinal Chemistry laboratory and support from Organic Synthetic laboratory III, Faculty of Chemistry, VNU University of Science Chapter : OVERVIEW 2-H Chromenes are an important class of oxygenated heretocyclic compounds Many biologically active natural products contain a chromene ring system ( Figure 2) In recent years, there has been increased interest in the synthesis of 2H-chromenes due to number of compounds that possesses this group, and that shows a variety of activities including as antidepressant, antihypertensive, antitubulin, antiviral , antioxidative, activator of potassium channels and inhibition of phosphodiesterase IV or dihydrofolate reductase Based on the importance of these compounds, a number of research groups have developed methodologies to synthesize these compounds The approaches used include intramolecular cyclization of Wittig intermidates, microwave assisted reaction of salicyaldehyde with enamines, catalytic Petasis reaction of salicyaldehydes, ring-closing olefin metathesis, Baylis-Hilman reaction of 2-hydroxy-benzaldehydes with methy vinyl ketones, Claisen rearrangement of propargyl phenol esters, Pd-catalyzed ring closure of 2-isoprenyl phenols, electrocyclic ring closure of vinylquinone derivatives, and the Ylid annulation reaction Despite the availability of these exisiting methods for the synthesis of chromene derivatives, there remains a demand for general strategies that can more efficiently provide variously substituted chromenes system Herein, I didn’t give all the methods that listed above but reported typical and efficient ones Figure : Compounds with 2H-Chromene skeleton 1.1 Application methods to synthesize nitro- chromene derivatives Synthesis of Pichromene and its derivatives is basically based on the synthesis of 2H-chromene and analogs This section lists out some routes which are used popularly to prepare chromene 1.1.1 Condensation between salicyaldehyde and α,β unsaturated compounds using organocatalysts This method is considered as one of the most popular and effective ones to synthesize 2-H chromenes and its derivatives by based catalyzed condensation of salicyaldehyde with deficient electron compounds such as ankenes, allenes The reaction is carried under the presence of bases such as triethyl amin, pyridine or DABCO (1,4 –diazabicyclo [ 2,2,2] octane ) which gave different results In 1978, Tohru Sakakibara introduced the synthesis of 3-nitro-2-phenyl-2H-chromene using triethyl amin as basic catalyst, but it resulted both chromene with a modest yield 38% and also a side product up to 31% was formed in chromanol (scheme 1) [1] Scheme : Syntheis of 3-nitro-2-phenyl-2H-chromene reported by Sakakibara The reaction between salicyaldehyde with electron deficient olefin was also studied by a group of Bhaskar C Das As reported (2010), with the same procedure above and extended to other different positioned substituents of salicyaldehyde by using 1,1,3,3- tetramethylguanidine (TMG ) and L- pipecolinic acid as organocatalyst, 3substituted -2-phenyl-2H-chromene derivatives were synthesized with high yield and poor enantioselectivity using pipecolinic acid while TMG works well with cynamaldehyde without using co-catalyst( Scheme 2)[2] Scheme : Synthesis of 2-H chromene derivatives using catalysts In 2001, Ming-Chung Yan and his co-workers postulated an easy and efficient method for the synthesis of 2,2-dialkyl-3-nitrochromene where the reaction between salicyaldehyde and β-nitrostyrene underwent with the presence of DABCO as catalyst and the absence of solvent at 40oC and it gave a range of high yield In the case below, the yield is quite impressive which is up to 99% as reported (Scheme 3)[3] Scheme 3: Synthesis of 2-H Chromene using DABCO as catalyst One year later, in 2002, Perry T Kaye also proposed a convenient general synthesis of 3-substituted 2H chromene derivatives using DABCO catalyzed which follows a Baylis- Hilman pathway.[4], [5] 1.1.2 Ring-closing metathesis for the synthesis of Chromene In 1997, Sukbok Chang reported a practical and highly efficient procedure for preparing diverse chromene derivative using ring closing metathesis ( RCM), a methodology emerging as a new tool in synthetic organic chemistry.[6] RCM of the dienes pre-prepared was next attempted using organometallic catalysts For example ruthenium carbene catalyst [ Cl2(PCy)3Ru=CHPh] (Scheme 4) Scheme 4: Ring-closing metathesis for the synthesis of Chromene This method gives a good yield but it’s quite costly and the preparation of starting materials meets some difficulties However, it’s still a new approach to generate various substituted chromene system 1.1.3 Microwave assisted synthesis of 3- Nitro-2H-chromene under solventless phase transfer catalytic conditions In 2008, Rafik Koussini and his colleague Ayed S Al-Shihri reported a treatment of substituted 2-hydroxy benzaldehyde with 2-nitro ethanol supported on anhydrous potassium carbonate, in presence of catalytic amount of tetrabylammonium bromide (TBAB) leads to the synthesis of 3-nitro-2H chromene 10 -Synthesis of 3-(4-chlorophenyl)-2-nitro-3H-benzo [f]chromene Reaction follows the general procedure Column chromatography : ethyl acetate/ n-hexane = 1/10 H-NMR (CDCl3, 300MHz) : 8.65(s, 1H), 7.94(d, J=8.44,1H,CH), 7.84(d, J=13.69Hz,1H,CH), 7.74(d,J=8.91,1H,CH), 7.67(d,J=8.10,1H,CH), 7.54-7.50(m, 1H,CH), 7.37-7.30(m,1H,CH), 7.26-7.24(m,1H,CH), 7.15-7.13(m,1H,CH), 6.59(s,1H,CH) 13 C-NMR (CDCl3, 300MHz) : 137.63, 137.46, 135.62, 130.26, 129.77, 129.51, 129.12, 129.06, 128.73, 128.41, 125.99, 125.21, 124.53, 124.39, 121.17, 119.21, 118.63, 117.79, 73.44 -Synthesis 2-nitro-3-(4-nitrophenyl)-3H-benzo[f] chromene Reaction follows the general procedure Column chromatography : ethyl acetate/ n-hexane = 1/10; H-NMR (CDCl3, 300MHz) : 8.71(s,1H), 8.04(d, J=8.87Hz,1H,CH), 7.95(d,J=8.46Hz,1H,CH),7.80(d,J=8.91Hz,1H,CH),7.71(d,J=8.12Hz,1H,CH),7.5 8-7.49(m,1H,CH), 7.40-7.36(m,1H,CH), 7.17(s,1H,CH), 6.72(s,1H,CH) 13 C-NMR (CDCl3, 300MHz) : 136.07, 131.23, 129.05, 129.19, 128.97, 127.80, 126.51, 126.49, 125.11, 124.52, 124.03, 123.23, 119.89, 119.37, 118.63, 117.52, 112.87, 114.81, 72.96 32 3.3.2 Synthesis of ethyl cinnamate 14.8 g cinnamic acid was added with 88ml of ethanol together with 2-3 drops of concentrated H2SO4 The mixture was refluxed for hours Then NaHCO310% was added to neutralize excess acid The solution was washed with water and NaCl Na2SO4 was used to eliminate water later H-NMR (CDCl3, 300MHz) 7.69(d, J=16.01Hz,2H,CH), 7.54-7.51(m, 2H,CH), 7.40-7.37(m,2H,CH),7.26(s,1H,CH),6.44(d,J=16.01Hz,1H,CH=C=O),4.27(q, J=7.14Hz, J=14.27Hz ,2H, CH2), 1.34(t, J=7.12Hz, 3H,CH3) 3.3.3.Synthesis of methyl 3-(4-fluorophenyl) acrylate The synthesis of 3-(4-fluorophenyl) acrylate includes steps Step : Wittig reaction 6.28 g trimethylphosphine was dissolved in 12ml of toluene in a necked flask, a pre-prepared solution of 4g methyl bromoacetate in 12ml of toluene was added dropwise into the former solution, a white precipitate was obtained The solution was reflux for hour The solid was collected by filtration and washed with hexane The product was dissolved in approximately 140ml of water in another round bottom An equal amount of toluene as water (140ml) was added 2-3 drops of phenolphthalein was put into the solution An enough amount of NaOH 2.5M was added to bring the mixture to the endpoint Then two layers were separated through a separatory funnel and solvent was eliminated by rotavapor And a white precipitate was obtained Step : Synthesis of methyl cinnamate derivative About 1.06ml of 4-fluorobenzaldehyde was added into 100ml round bottom flask equipped with a stir bar 50ml of CH2Cl2 was added later and the mixture was stirred in 10 in an ice bath 5.0g of the phosphorane was added and stirred for another 10 and the solution was cooled to the room temperature and placed overnight CH2Cl2 was removed by rotar vapor and a yellow precipitated was obtained 50 ml of hexane was added to the residue in the flask, and break up the suspension with a glass rod, the mixture then was filtered into a clean fask and another 50ml of hexane was used to rinse the flask Solvent was removed and the cinamate was collected finally 33 H-NMR (CDCl3, 300MHz) : 7.70-7.76(m, 1H), 7.53-7.51(m, 1H,CH), 7.28(s, 1H), 6.38(d, J=18.01Hz,1H), 3.82(s,3H,CH3) 13 C-NMR (CDCl3, 300MHz) : 167.32, 162.25, 143.58, 130.01, 129.89, 116.21, 115.92, 51.77 3.3.4 Synthesis of carboxylate chromenes derivative General procedure b: 0.5mmol of cinnamates as added with 0.5mmol of salicyaldehyde derivatives under solvents and catalysts The mixture was stirred vigorously at the temperature 80oC or room temperature 34 CONCLUSION -The thesis is a compilation of the synthesis to prepare 2H-chromene derivatives and from that to apply to synthesize the derivatives of 3-nitro-2phenyl-2H-chromene and carboxylate chromene - The optimal condition which was investigated before to synthesize 3-nitro-2phenyl-2H-chromene compounds was applied to get a series of nitro-chromene derivative Seven compounds of the series were synthesized and confirmed by spectroscopic data -The thesis also focused on the synthesis of carboxylate chromenes derivatives, trials with conditions which were applied on the carbaldehyde chromene were also tested but unfortunately, the results didn’t give a positive outlook 35 REFERENCES K Hayashi, J Mori, H Saito, T Hayashi, Biol Pharm Bull, 2006, 29(9), 1843 – 1847 J M Batista Jr., A A Lopes, D L Ambrosio, L O Regasini, M J Kato, V.Bolzani, R M B Cicarelli, M Furlan, Biol Pharm Bull , 2008, 31(3), 538 – 540 Hu, H.; Harrison, T J.; Wilson, P D., J Org Chem., 2004, 69, 3782 – 3786 K C Nicolaou, J A Pfefferkorn, A J Roecker, G.Q Cao, S Barluenga, H J Mitchell, J.Am.Chem.Soc , 2000, 122, 9939 – 9953 X.Mao, B Cao, T E Wood, R Hurren, J Tong, X Wang, W.Wang, J Li, Y Jin,W Sun, P.A Spagnuolo, N MacLean, M F Moran, A Datti, J Wrana, R A Batey, A D Schimmer, BLOOD , 2011, 117, 6, 1986 – 1997 Conti, C.; Desideri, N., Bioorganic & Medicinal Chemistry, 2010, 18, 6480 – 6488 van Otterlo, W A.; Ngidi, E L.; Kuzvidza, S.; Morgans, G L.; Moleele, S S.; de Koning, C B., Tetrahedron, 2005, 61, 9996 – 10006 E Sekino, T Kumamoto, T Tanaka, T Ikeda, T Ishikawa, J Org Chem , 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SPECTROSCOPIC DATA 6,8-dibromo-3-nitro-2-(3,4,5-trimethoxyphenyl)-2H-chromene H -NMR 13 C- NMR 38 8-ethoxy-3-nitro-2-(3,4,5-trimethoxyphenyl)-2H-chromene H- NMR 13 C- NMR 39 6-bromo-3-nitro-2-(3,4,5-trimethoxyphenyl)-2H-chromene H NMR 13 C- NMR 40 8-bromo-3-nitro-2-(3,4,5-trimethoxylphenyl)-2H-chromene H -NMR 13 C -NMR 41 3-(4-bromophenyl)-2-nitro-3H-benzo[f] chromene H -NMR 13 C- NMR 42 3-(4-chlorophenyl)-2-nitro-3H-benzo [f]chromene H -NMR 13 C -NMR 43 2-nitro-3-(4-nitrophenyl)-3H-benzo[f] chromene H- NMR 13 C -NMR 44 methyl 3-(4-fluorophenyl) acrylate H-NMR 13 C -NMR 45 Ethyl cinnamate H-NMR 46 [...]... 7.80(d,J=8.91Hz,1H,CH), 7. 71( d,J=8 .12 Hz,1H,CH),7.58-7.49(m,1H,CH), 7.40-7.36(m,1H,CH), 7 .17 (s,1H,CH), 6.72(s,1H,CH) 13 6.07, 13 1.23, 12 9.05, 12 8.97, 12 7.80, 12 6. 51, 12 5 .11 , 12 4.52, 12 4.03, 11 9.89, 11 9.37, 11 8.63, 11 2.87, 11 4. 81, 72.96 12 9 .19 , 12 6.49, 12 3.23, 11 7.52, Table 2: 1H-NMR and 13 C-NMR data of 3-nitro-2-phenyl-2H-chromene derivatives 24 2.2 .1 Synthesis of 2-phenyl-2H-chromene carboxylate derivatives. .. 8.65(s, 1H), 7.94(d, J=8.44,1H,CH), 7.84(d, J =13 .69Hz,1H,CH), 7.74(d,J=8. 91, 1H,CH), 7.67(d,J=8 .10 ,1H,CH), 7.54-7.50(m, 1H,CH), 7.37-7.30(m,1H,CH), 7.26-7.24(m,1H,CH), 7 .15 -7 .13 (m,1H,CH), 6.59(s,1H,CH) 13 7.63, 13 7.46, 13 5.62, 12 9.77, 12 9. 51, 12 9 .12 , 12 8.73, 12 8. 41, 12 5.99, 12 4.53, 12 4.39, 12 1 .17 , 11 8.63, 11 7.79, 73.44 13 0.26, 12 9.06, 12 5. 21, 11 9. 21, 7 8. 71( s,1H), 8.04(d, J=8.87Hz,1H,CH), 7.95(d,J=8.46Hz,1H,CH),... 7.95(d,J=8.46Hz,1H,CH),7.80(d,J=8.91Hz,1H,CH),7. 71( d,J=8 .12 Hz,1H,CH),7.5 8-7.49(m,1H,CH), 7.40-7.36(m,1H,CH), 7 .17 (s,1H,CH), 6.72(s,1H,CH) 13 C-NMR (CDCl3, 300MHz) : 13 6.07, 13 1.23, 12 9.05, 12 9 .19 , 12 8.97, 12 7.80, 12 6. 51, 12 6.49, 12 5 .11 , 12 4.52, 12 4.03, 12 3.23, 11 9.89, 11 9.37, 11 8.63, 11 7.52, 11 2.87, 11 4. 81, 72.96 32 3.3.2 Synthesis of ethyl cinnamate 14 .8 g cinnamic acid was added with 88ml of ethanol together with 2-3 drops of. .. 12 3.64, 11 9.76, 11 1.54, 10 3.87, 74.09, 60.79, 56.22 5 8.67 (s,1H), 7.95(d, J= 8.45Hz,1H), 7.83(d, J =13 .69Hz,1H),CH) 7.75(d, J=8.92Hz,1H,CH),7.69(d, J=8.92,1H,CH), 7.567.48(m, 1H,CH), 7.38-7.28(m,1H,CH), 7.207 .16 (m,1H,CH), 7.68(d, J=8.93,1H,CH) 6.59(s,1H,CH) 15 3.49, 13 9 .16 , 13 7.72, 13 5.63, 13 2.76, 13 2.02, 13 0.37, 12 9 .12 , 12 8.73, 12 6. 01, 12 5.22, 12 4.53, 12 1 .18 , 11 7.79, 73.49 13 7. 51, 13 0.92, 12 8.67 12 3.70,... (ppm) δ1H NMR (ppm) 15 3.39, 14 9.57, 14 2. 81, 13 9.03, 7.93(s, 1H),7.68-7.67 (m,H, CH)3. 81( s, 3H, 13 1 .12 , 12 7.36, 12 0.93, 11 4.77, CH3), 3.79(s, 6H, CH3) 11 2.43, 10 3.93, 74.27, 60.79, 56.28 8.02(s, 1H), 6.96-6. 91( m, 3H), 6.62(s, 2H) 15 3.29, 14 7.96, 14 3 .15 , 14 1.50, 4.04(q, J=7 .12 Hz, J=8.67Hz), 3.78 (s, 6H, CH3), 13 8.70, 13 2 .19 , 12 9.42, 12 2 .14 3.76 (s, 3H, CH3), 1. 38(t, J=6.66Hz) 11 9 .16 , 11 8. 41, 10 3.93,... 1/ 10 1 H-NMR (CDCl3, 300MHz) : 8.67 (s,1H), 7.95(d, J= 8.45Hz,1H), 7.83(d, J =13 .69Hz,1H),CH) 7.75(d, J=8.92Hz,1H,CH),7.69(d, J=8.92,1H,CH), 7.567.48(m, 1H,CH), 7.38-7.28(m,1H,CH), 7.20-7 .16 (m,1H,CH), 7.68(d, J=8.93,1H,CH) , 6.59(s,1H,CH) 13 C-NMR (CDCl3, 300MHz) : 15 3.49, 13 9 .16 , 13 7.72, 13 7. 51, 13 5.63, 13 2.76, 13 2.02, 13 0.92, 13 0.37, 12 9 .12 , 12 8.73, 12 8.67 12 6. 01, 12 5.22, 12 4.53, 12 3.70, 12 1 .18 , 11 7.79,... 300MHz) : 13 7.63, 13 7.46, 13 5.62, 13 0.26, 12 9.77, 12 9. 51, 12 9 .12 , 12 9.06, 12 8.73, 12 8. 41, 12 5.99, 12 5. 21, 12 4.53, 12 4.39, 12 1 .17 , 11 9. 21, 11 8.63, 11 7.79, 73.44 -Synthesis 2-nitro-3-(4-nitrophenyl)-3H-benzo[f] chromene Reaction follows the general procedure Column chromatography : ethyl acetate/ n-hexane = 1/ 10; 1 H-NMR (CDCl3, 300MHz) : 8. 71( s,1H), 8.04(d, J=8.87Hz,1H,CH), 7.95(d,J=8.46Hz,1H,CH),7.80(d,J=8.91Hz,1H,CH),7. 71( d,J=8 .12 Hz,1H,CH),7.5... 56.05, 14 .77 7.99(s, 1H), 7.48-7.42(m, 2H),7.28(s, 1H) 15 3.56, 15 2.49, 14 1.90, 13 9.29 6.82(d, J=8.58Hz, 1H), 3.830(s,3H CH3), 13 6.72, 13 2.26, 13 1.66, 12 7.67, 3.803(s, 6H, CH3) 11 9.04, 11 4.49, 10 4.35, 74.56, 60.79, 56.23 7.98(s, 1H), 7.48-7.42(m, 2H), 7.29(s,1H) 15 3.39, 15 0.42, 14 2.06, 13 8.85, 6.82(d,J=8.58Hz,1H),6.58(d,J =10 .38Hz, 1H ), 13 7.35, 13 1.70, 12 9.52, 12 8.65, 3.830(s,3H, CH3), 3,803(s,6H, CH3) 12 3.64,... 4.04(q, J=7 .12 Hz, J=8.67Hz), 3.78 (s, 6H, CH3), 3.76 (s, 3H, CH3), 1. 38(t, J=6.66Hz) 13 C-NMR (CDCl3, 300MHz) : 15 3.29, 14 7.96, 14 3 .15 , 14 1.50, 13 8.70, 13 2 .19 , 12 9.42, 12 2 .14 , 11 9 .16 , 11 8. 41, 10 3.93, 73.62, 64.98, 60.75, 56.05, 14 .77 -Synthesis of 6-bromo-3-nitro-2-(3,4,5-trimethoxyphenyl)-2H-chromene Reaction follows the general procedure Column chromatography : ethyl acetate/ n-hexane = 1/ 10 1 H-NMR... 3-nitro-2-phenyl-2H-chromene Entry R1 R2 Ratio Product Yield 1 3,5- 3,4,5- 1: 1 46% dibromo trimethoxy 2 3-ethoxy 3,4,5trimethoxy 1: 1 61% 3 5-bromo 3,4,5- 1: 1 52% trimethoxy 4 3-bromo 3,4,5trimethoxy 1: 1 33% 5 1- naphtha 1- bromo 1: 1 45% 6 1- naphtha 1- chloro 1: 1 40% 21 7 1- naphtha 1- nitro 1: 1 44% Table 1 : Condensation products between salicyaldehydes and α,β-nitrostyrene The derivatives of 3-nitro-2-phenyl-2H-chromenes products ... 7.40-7.36(m,1H,CH), 7 .17 (s,1H,CH), 6.72(s,1H,CH) 13 6.07, 13 1.23, 12 9.05, 12 8.97, 12 7.80, 12 6. 51, 12 5 .11 , 12 4.52, 12 4.03, 11 9.89, 11 9.37, 11 8.63, 11 2.87, 11 4. 81, 72.96 12 9 .19 , 12 6.49, 12 3.23, 11 7.52,... 7 .17 (s,1H,CH), 6.72(s,1H,CH) 13 C-NMR (CDCl3, 300MHz) : 13 6.07, 13 1.23, 12 9.05, 12 9 .19 , 12 8.97, 12 7.80, 12 6. 51, 12 6.49, 12 5 .11 , 12 4.52, 12 4.03, 12 3.23, 11 9.89, 11 9.37, 11 8.63, 11 7.52, 11 2.87, 11 4. 81, 72.96... C-NMR (CDCl3, 300MHz) : 13 7.63, 13 7.46, 13 5.62, 13 0.26, 12 9.77, 12 9. 51, 12 9 .12 , 12 9.06, 12 8.73, 12 8. 41, 12 5.99, 12 5. 21, 12 4.53, 12 4.39, 12 1 .17 , 11 9. 21, 11 8.63, 11 7.79, 73.44 -Synthesis 2-nitro-3-(4-nitrophenyl)-3H-benzo[f]