Tetrahedron Letters 54 (2013) 2920–2923

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One pot imino Diels–Alder reaction for the synthesis of 3-aryl-3,4-dihydro- benzo[f]quinoline derivatives catalyzed by antimony trichloride

Gourhari Maiti ⇑, Rajiv Karmakar, Utpal Kayal Department of Chemistry, Jadavpur University, Kolkata 700 032, India

a r t i c l e i n f o

Article history:Received 1 October 2012 Revised 21 March 2013 Accepted 22 March 2013 Available online 3 April 2013

Keywords:NaphthylamineBut-2-ynedioateImino Diels–Alder reaction Multicomponent reaction 3-Aryl-3,4 dihydrobenzoquinoline-1,2- dicarboxylateAntimony trichloride

0040-4039/$ - see front matter � 2013 Elsevier Ltd. Ahttp://dx.doi.org/10.1016/j.tetlet.2013.03.093

⇑ Corresponding author.E-mail address: ghmaiti123@yahoo.co.in (G. Maiti

a b s t r a c t

An one pot simple and efficient approach toward the synthesis of dialkyl-3-aryl-3,4-dihydro- benzo[f]quinoline-1,2-dic arboxylate and its dehydro derivatives have been developed through the three-com ponent reaction of aromatic aldehydes, 2-naphthylamine, and but-2-ynedioate catalyzed bySbCl3 under reflux in acetonitrile in good to excellent yields.

� 2013 Elsevier Ltd. All rights reserved.

The current trends of synthetic organic chemistry are found toinvolve wide applications of multicompone nt reactions (MCRs) inorder to develop efficient and practical methods for the synthesis of structura lly diverse molecules.1 Metal catalyzed MCRs involving cascade C–C and C–N bond formatio ns have been greatly used inthe synthesis of a range of heterocycles. This powerful technique has emerged as a greener approach for the preparati on of bioactive compounds in much shorter time with minimum waste production and also to increase the synthetic efficiency by reducing the number of steps.2

The quinoline and benzoquinolin e nuclei are prominent struc- tural motifs found in numerous natural products and synthetic compounds with important pharmacolo gical and biologica l activ- ities. The quinoline and benzo[ g]quinoline ring and their analogs behave as agonists at the D2-site in schizophrenia.3 The benzo- quinoline core structure is found in a wide variety of biologically active natural products and pharmaceuti cals with antimicrobi al,4

antibacterial ,5 antipsychot ic,6 agonistic,7 antimala rial,8 antitu-mor,9 and uridine diphosph ate (UDP)-glucuronosyl transferase 10

activities.All the above aspects have attracted attention of organic

chemists to develop efficient synthetic routes to highly functional- ized benzoquinol ine derivatives for several decades.11 Theimino Diels–Alder (IDA) reaction provides an easy access for the

ll rights reserved.

).

preparati on of six-membered nitrogen heterocycl es as well asrelated fused ring heterocycles .12,13 In recent years, this reaction has been found to have wide applications through the activation of the imine systems for cycloadditions by increasing their electron- deficient character.14 Although, several Lewis acid and Brønsted acid catalyzed imino Diels–Alder reactions have been develope d15 as convenient routes for the construction of a wide variety of nitrogen heterocycl es, there is further scope for develop- ment of this methodology .

Very recently, Wang et al.16 have reported a one-pot synthesis of 3-arylbenzo [f]quinoline-1,2-d icarboxylate derivatives via animino Diels–Alder reaction catalyzed by Yb(OTf)3. To the best ofour knowledge, there is no report of the use of antimony trichloride (SbCl3), a mild and inexpensive catalyst, for imino Diels–Alderreaction using electron- deficient dienophiles like dialkyl acetylene dicarboxy lates. Recently , we have efficiently utilized this catalyst for such reaction using electron rich dienophiles .17 Our recent suc- cess in effective utilization of this catalyst for IDA reaction using electron rich olefins coupled with our continuous effort toward synthesis of bioactive heterocycl ic compounds 18 encourag ed usto study a three-component reaction using naphthylamine s,aromatic aldehydes, and dialkyl acetylene dicarboxyla tes. This study resulted in the developmen t of an efficient synthetic route to 3-aryl-3,4-di hydrobenzo[ f]quinoline-1,2-d icarboxylate and 3-arylbenzo [f]quinoline-1,2- dicarboxylate (dehydro derivative ofthe former) via an imino Diels–Alder reaction. It may be mentioned here that antimony(III) salts 19 (chloride and sulfate) have been

4a 5a

NH2 CHO+ +

CO2Me

CO2Me

NH

CO2MeMeO2C

N

CO2MeMeO2C

SbCl3 (10 mol %)

CH3CN, 80 0C +

1a 2a 3aargon atm.

Scheme 1. Synthesis of benzoquinoline derivative.

Table 1Optimization of reaction conditions a

NH

MeO2C

MeO2C

N

MeO2C

MeO2C

+

4a 5a

NH2

+

CO2Me

CO2Me1a(1 equiv.) 3a (1.2 equiv.)

CHO

2a(1 equiv.)

Catalyst (10 mol %)CH3CN,80 0C,argon atm.

+

Entry Catalyst (mol %) Solvent T (�C) Product ratio (4a:5a) Time (h) Yield b (%)

1 Sbcl 3/1 CH3CN 80 4:1 9 762 Sbcl 3/10 CH3CN 80 8:1 6 903 Sbcl 3/5 CH3CN 80 5:1 7 794 Sbcl 3/10 CH3CN 50 3:1 8 625 Sbcl 3/10 Toluene 90 3:1 9 506 Sbcl 3/10 DMF 90 5:2 9 357 Sbcl 3/10 THF 80 7:3 8 408 nil/10 CH3CN 80 — 12 c

9 lncl 3/10 CH3CN 80 5:1 12 4210 Fecl 3/10 CH3CN 80 4:1 10 4511 CAN/10 CH3CN 80 9:4 14 3912 Sncl 4/10 CH3CN 80 5:1 16 4113 Agcl/10 CH3CN 80 3:1 14 4014 Zncl 2/10 CH3CN 80 7:3 18 50

a Reaction condition: benzaldehyde (1.0 mmol), naphthalen-2-amine (1.0 mmol), dimethyl but-2-ynedioate (1.2 mmol), catalyst, in 2 mL solvent.b Pure, isolated yield after column chromatography.c No product was isolated.

G. Maiti et al. / Tetrahedron Letters 54 (2013) 2920–2923 2921

used by us as well as others as mild and efficient catalysts for var- ious organic transformat ions.

In a preliminary study, the treatment of 2-naphthyla mine 1a,benzaldehyd e 2a, and dimethyl but-2-ynedioa te 3a in refluxing ace- tonitrile in the presence of 10 mol % SbCl 3 under argon atmosphere for 8 h furnished a mixture of two compound s, dimethyl 3-phenyl- 3,4-dihydro benzo[ f]quinoline- 1,2-dicarboxy- late 4a and dimethyl 3-phenylbe nzo[ f]quinoline-1,2-d icarboxy-late 5a (Scheme 1) in aratio of 8:1 in 90% overall yield. With this encourag ing result, we ex- plored to optimize the reaction conditions using SbCl 3 and other Le- wis acid catalysts, the results of which are summarized in Table 1. Itis apparent from Table 1 that among various Lewis acid catalysts such as InCl 3, FeCl 3, SbCl 3, ZnCl 2, AgCl, ceric ammonium nitrate (CAN), and SnCl 4, SbCl 3 (10 mol %) was the best one to give maxi- mum yield of products.

By variation of the solvent used for this reaction (Table 1), ace- tonitrile was found to be the most suitable one. In a separate experiment, the reaction was carried out in open air for 24 h and it was found that even under this condition compound 4a wasformed as a major product (4a:5a = 3:2) in good overall yield (89%). It is noteworthy that when the reaction of 2-naphthyla mine 1a, 4-chlorobenza ldehyde 2c, and dimethyl but-2-ynedioa te 3awas allowed to reflux in acetonitrile in the presence of 10 mol %of SbCl 3 for 24 h under the balloon pressure of air, compound 5cwas isolated in 87% yield along with compound 4c as minor prod- uct (yield ca. 4%). The Yb(OTf)3 catalyzed version of this reaction,16

however , yielded 3-arylbenzo [f]quinoline-1,2-d icarboxylate (fullyaromatiz ed compound ) as the sole product in open air. Therefore,a special feature which needs mentioni ng here is that in our reac- tion condition, we could isolate the dihydro derivatives as the ma- jor product even without taking any precaution to exclude air.

To extend the applicability of the method, various aromatic aldehydes 2b–n, 2-naphthyla mine 1a, and acetylene diesters 3a–b were subjected to similar reaction conditions and the results are summarized in Table 2. All the aromatic aldehydes either bear- ing electron-do nating groups (such as methyl, methoxy, methyl- enedioxy, etc.) or electron-wi thdrawing groups (such as fluoro,chloro, bromo, nitro, etc.) gave the expected products in very good yields under the reaction conditions.20 4-N,N-Dimethylami nobenz- aldehyde (Table 2, entry 8) did not respond to the reaction most probably due to the strong +R effect of dimethylam ino group which decreases the reactivity of the aldehyde group significantly.

In order to assess the scope of this reaction, 1-naphthylam ine 1b was treated separately with the aromatic aldehydes 2f and 2nand dimethyl but-2-yn oate 3a under similar reaction conditions.This variation furnished mixtures of corresponding dimethyl 2-aryl-1,2-dihydrobenzo[ h]quinoline-3,4-d icarboxylate 4o–p anddimethyl 2-arylbenzo[ h]quinoline-3,4-d icarboxylate 5o–p in very good yield (Table 3).

For further study in this area, aliphatic aldehydes such as but- anal and octanal were used in place of aromatic aldehydes under similar reaction conditions to react with 1a and 3a. However, such

Table 2One-pot synthesis of 3-aryl-3,4-dihydrobenzo[ f]quinoline-1,2-dicarboxylate catalyzed by SbCl 3a

NH

R1R2O2C

R2O2C

+

4a-p 5a-p

NH2

+

CO2R2

CO2R2

1a 3a-b2a-p

+SbCl3 (10 mol %)

CH3CN, 80 0CR1

CHO

N

R2O2C

R2O2CR1

argon atm.

Entry R1 R2 Product ratio c (4:5) Time (h) Yield b (%)

1 H Me 4a:5a = 8:1 6 902 4-Methoxy Me 4b:5b = 6:1 8 833 4-Chloro Me 4c:5c = 7:2 6 864 4-Nitro Me 4d:5d = 7:1 6 885 2,6-Dichloro Me 4e:5e = 5:1 7 816 3-Niro Me 4f:5f = 9:2 7 827 2,3,4-Trimethoxy Me 4g:5g = 5:1 10 788 4-Dimethylamino Me — 12 —9 2,4-Dichloro Me 4h:5h = 6:1 8 8410 3-Bromo Me 4i:5i = 4:1 6 8611 3,4-Dimethoxy Me 4j:5j = 4:1 9 8012 2,3-Phenyl Me 4k:5k = 4:1 7 8513 3,4-Methylenedioxy Me 4l:5l = 7:1 8 8014 4-Fluoro Et 4m:5m = 6:1 6 8915 4-Methyl Et 4n:5n = 6:1 8 84

a Reaction condition: benzaldehyde (1.0 mmol), naphthalen-2-amine (1.0 mmol), dimethyl but-2-ynedioate (1.2 mmol), catalyst (0.1 mmol) in 2 mL solvent.b Products were characterized by mp, IR, 1H NMR and 13C NMR, HRMS.c The product ratio was determined on the basis of the isolated pure compound.

Table 3One-pot synthesis of dimethyl-2-phenyl-1,2-dihyd robenzo[ h]quinoline-3,4-dicarboxylate catalyzed by SbCl 3a

NH2 CHO

R1

CO2Me

CO2Me

+ +

SbCl3 (10 mol%)

CH3CN, 80 0C

HN

CO2Me

CO2MeN

CO2Me

CO2Me

R1R1

+

1b 2 3a 4o-p 5o-p

argon atm.

Entry R1 Product ratio c (4:5) Time (h) Yield b (%)

1 3-Nitro (2f) 4o:5o = 7:1 7 802 4-Methyl (2n) 4p:5p = 5:2 6 77

a Reaction condition: benzaldehyde (1.0 mmol), naphthalen-1-amine (1.0 mmol), dimethyl but-2-ynedioate (1.2 mmol), catalyst (0.1 mmol) in 2 mL solvent.b Products were characterized by mp, IR, 1H NMR and 13C NMR, HRMS.c The product ratio was determined on the basis of the isolated pure compound.

2922 G. Maiti et al. / Tetrahedron Letters 54 (2013) 2920–2923

combinations furnished complex reaction mixtures from which any desired product could not be isolated. Possibly, facile aldol condensation involving aliphatic aldehydes is responsible for such result.

In conclusio n, we have developed a mild, simple, and efficientmethodology for one pot imino Diels–Alder reaction of N-arylimines with dimethyl but-2-ynedioa te by use of SbCl 3 as catalyst.The reaction afforded a variety of novel 3-aryl-3,4-di hydro-benzo- quinoline-1 ,2-dicarboxyla te derivatives along with their dihydro derivatives in good to excellent yield. The notable advantages of this method are operational simplicity, use of inexpensive catalyst, ease of product isolation, and ability to synthesize a library ofdihydrobenzoq uinoline derivatives, which might have potential biological activity.

Acknowled gments

We thank the Department of Chemistry, Jadavpur University for financial and infrastructu ral support from PURSE-DST programme.R.K. and U.K. thank CSIR, New Delhi for award of fellowship .

Supplemen tary data

Supplement ary data (experimental procedures and spectral data) associated with this article can be found, in the online ver- sion, at http://dx .doi.org/10.1016/j .tetlet.2013.03.093 .

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20. Representative experimental procedure for the synthesis of dimethyl 3-phenyl-3,4- dihydrobenzo[f]quinoline-1,2-dicarboxylate (4a): A magnetically stirred mixture of benzaldehyde (100 mg, 1.0 mmol), naphthalene-2-amine (134 mg,1.0 mmol), dimethyl acetylene dicarboxylate (159 mg, 1.2 mmol), and anhydrous antimony trichloride (22 mg, 0.10 mmol) in dry acetonitrile (3 mL) under argon was refluxed for 6 h (monitored by TLC). The solvent was removed under reduced pressure and the residue obtained was purified bycolumn chromatography over silica gel (18% ethyl acetate in petroleum ether)yielded 4a (315 mg, 80%) and 5a (39 mg, 10%). Compound 4a, mp 210 �C; IR(KBr): 3342, 2950, 1718, 1702, 1619, 1604, 1561, 1431, 1237, 1205, 1097,821,754 cm�1. 1H NMR (300 MHz, CDCl 3): d 3.79 (s, 3H), 3.95 (s, 3H), 5.64 (br s,1H), 6.80 (d, J = 8.7 Hz, 1H), 7.20–7.26 (m, 4H), 7.37 (m, 3H), 7.61 (t, J = 9.0 Hz,2H), 7.84 (d, J = 8.7 Hz, 1H). 13C NMR (CDCl3, 75 MHz): d 52.3, 52.5, 52.7, 109.8,114.9, 116.9, 122.1, 122.9, 126.3, 127.7, 127.8, 128.3, 128.5, 129.2, 131.5, 134.0,139.6, 141.8, 144.5, 165.0, 170.4. HRMS (ES+): calcd for [C23H19NO4] Na+:396.1206; found: 396.1202. Compound 5a (39 mg, 10%), mp: 147–148 �C; IR(KBr): 2956, 1747, 1718, 1548, 1443, 1435, 1241, 1005, 964, 842, 811, 766,740 cm�1. 1H NMR (300 MHz, CDCl 3): d 3.71 (s, 3H), 4.10 (s, 3H), 7.48–7.51 (m,3H), 7.64–7.68 (m, 2H), 7.70–7.73 (m, 2H), 7.94–7.97 (m, 1H), 8.06 (s, 2H),8.27–8.30 (m, 1H). 13C NMR (CDCl3, 75 MHz): d 52.9, 53.5, 119.5, 124.2, 125.2,127.4, 127.9, 128.2, 128.3, 128.5, 129.1, 129.4, 132.9, 133.5, 138.4, 139.6, 149.7,156.0, 168.3, 169.6. HRMS (ES+): calcd for [C23H17NO4] Na+: 394.1050; found:394.1053.