Sulfated polyborate: An efficient and reusable catalyst for one pot synthesis of Hantzsch 1,4-dihydropyridines derivatives using ammonium carbonate under solvent free conditions

Accepted Manuscript Sulfated polyborate: an efficient and reusable catalyst for one pot synthesis of Hantzsch 1,4-dihydropyridines derivatives using ammonium carbonate under solvent free conditions Deelip S. Rekunge, Chetan K. Khatri, Ganesh U. Chaturbhuj PII: DOI: Reference:

S0040-4039(17)30210-1 http://dx.doi.org/10.1016/j.tetlet.2017.02.038 TETL 48649

To appear in:

Tetrahedron Letters

Received Date: Revised Date: Accepted Date:

10 January 2017 10 February 2017 11 February 2017

Please cite this article as: Rekunge, D.S., Khatri, C.K., Chaturbhuj, G.U., Sulfated polyborate: an efficient and reusable catalyst for one pot synthesis of Hantzsch 1,4-dihydropyridines derivatives using ammonium carbonate under solvent free conditions, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.2017.02.038

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Graphical Abstract

Sulfated polyborate: an efficient and reusable catalyst for one pot synthesis of Hantzsch 1,4-dihydropyridines derivatives using ammonium carbonate under solvent free conditions Deelip S. Rekunge, Chetan K. Khatri, Ganesh U. Chaturbhuj*

1

Tetrahedron Letters journal homepage: www.elsevier.com

Sulfated polyborate: an efficient and reusable catalyst for one pot synthesis of Hantzsch 1,4-dihydropyridines derivatives using ammonium carbonate under solvent free conditions Deelip S. Rekunge, Chetan K. Khatri, and Ganesh U. Chaturbhuj∗ Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai- 400019 India.

ARTICLE INFO

ABSTRACT

Article history: Received Received in revised form Accepted Available online

A simple and efficient method for the synthesis of four-component 1,4-dihydropyridines of various aldehydes, β-ketoesters and ammonium carbonate catalyzed by sulfated polyborate with high yields under a solvent free condition at 90 °C is described. The key advantages of the present method are high yields, short reaction time, solvent free condition, easy workup, recyclability of catalyst and ability to tolerate a variety of functional groups which gives economical as well as ecological rewards.

Keywords: Catalyst Sulfated polyborate Dihydropyridine Ammonium carbonate

2016 Elsevier Ltd. All rights reserved.

——— ∗Corresponding author. Tel.: +91-223-361-2212; fax: +91-222-414-5614; e-mail: [email protected]

2 Over the several decades, nitrogen-containing sixmembered heterocycles are valuable in the field of pharmaceutical chemistry. As they exhibit significant pharmacological activity, these bioactive heterocycles, and their synthetic approaches have been important topics of interest to medicinal chemists. Among them, 1,4-dihydropyridines (1,4DHPs) are an important class of N-heterocyclic ring widely used in the field of pharmaceuticals.1,2 The heterocyclic unit 1,4-DHPs has remarkable pharmacological efficiency such as anticonvulsant, antidiabetic, antianxiety, antidepressive, antitumor, analgesic, sedative, vasodilator, bronchodilator, hypnotic, anti-inflammatory agents,3-7 neuroprotective, and neuropeptide YY1 antagonist activities.8 The 1,4-DHPs such as nifedipine, diludipine, and nitrendipine (Fig.1), have been proved to be an important class of calcium-channel blocker9,10 for the treating of cardiovascular diseases.11 Chiral sulfoxide DHPs are analogues of NADH coenzymes, and act as NADH mimics for the enantioselective reduction of carbonyl compounds.12,13 1,4DHPs have also proved to be very important synthetic intermediates in the preparation of a large number of alkaloids.14 Recently, studies showed that 1,4-dihydropyridine derivatives with lipophilic groups have considerable antitubercular activity against Mycobacterium tuberculosis H37Rv. The significant pharmacological activity of these compounds has not only attracted many medicinal chemists to synthesize this heterocycle but has also become an active research area. The classical synthesis of 1,4-DHPs by Hantzsch method involves one-pot condensation of an aldehyde with ethyl

Fig. 1. Pharmacologically active 1,4-dihydropyridines.

acetoacetate and ammonium acetate in refluxing alcohol.15 However, this procedure suffers from shortcomings such as low yields particularly in the case of aliphatic and unsaturated aldehydes and longer reaction times. Numerous modified methods have been reported,16,17 for the synthesis of 1,4-DHPs, which involves the use of reagents and catalysts such as silica sulphuric acid (SSA),18 nano-tungsten trioxide-supported sulfonic acid (n-WSA),19 silica sulfuric acid,20 BF3-SiO2 nanoparticles,21 sulfated boric acid nanoparticles,22 nano-sulfated zirconia,23 γFe2O3@SiO2-SO3H,24 p-TSA strongly accelerated by ultrasonic irradiation,25 silica gel/sulfonic acid catalyst (SiO2–SO3H),26 cellulose sulfuric acid,27 phenyl boronic acid,28 SiO2–NaHSO4,29 Ce(SO4)2-SiO2,30 AlCl3 6H2O,31 HClO4-SiO2,16 CeCl3 7H2O,32 Sc(OTf)3,33 TMS iodide,34 HY zeolite,35 Montmorillonite K10,36 Fe(III) trifluoroacetate,37 heteropoly acid K7[PW11CoO40],38 PPh3,39 TBAB,40 I2,41 2,4,6-trichloro[1,3,5]triazines (TCT, cyanuric chloride),17 ionic liquid/3,4,5-trifluorobenzeneboronic acid,42 and fermenting bakers’ yeast,43 under various conditions such as ultrasound,44 microwave irradiation,45 and high temperature,46 in refluxing toxic solvent etc.

Scheme 1. Schematic representation of sulfated polyborate catalyzed synthesis of 1,4-dihydropyridines.

However, many of these methodologies suffer from drawbacks such as long reaction times, harsh conditions, low product yields, extractive product isolation procedures with toxic organic solvents, expensive reagents, metal-based, toxic/corrosive catalysts, and difficulty in recovery and reusability of the catalysts. Therefore, there is a need for the development of a catalyst which is mild, recyclable, functional group compatible, and cost-effective for the synthesis of 1,4-dihydropyridines. A literature search revealed that boric acid catalyzes many useful organic transformations above 100 °C.47,48 Boric acid dehydrates above 100 °C and turns to its polymeric forms, which could be the active species catalyzing the reaction.49 Dehydrative polymerization of boric acid liberates water molecules which may hamper the progress of the reaction. This prompted us to develop a polymeric boric acid catalyst with mild Bronsted acidity. To accomplish this boric acid was dehydrated at 200 °C to convert it into its polymeric Lewis acid form and then sulfonated to introduce the mild Bronsted acid character.50 Boron being an electron deficient element and electron withdrawing effect of adjacent sulfate enhances its Lewis acidity; hence sulfated polyborate has both Lewis as well as Bronsted acid characters (Scheme 1). The development of novel synthetic procedures with a pursuit of green, catalytic, convenient and practical methods for organic synthesis to maximize efficiency and minimize waste been currently in demand. Recently we have synthesized and characterized sulfated polyborate and demonstrated its effectiveness as an acid catalyst for Biginelli reaction,50 Kabachnik-Fields reaction51 and quinoxalines synthesis,52 all under solvent- free condition. It's easy preparation, mild acidity, stability, reusability, and eco-friendliness has inspired us to explore its potential to catalyze many other useful reactions. To achieve these objectives, herein this report describes sulfated polyborate as an efficient and reusable catalyst for the synthesis of 1,4-dihydropyridines under a solvent free condition with high yields and non-extractive product isolation (Scheme 1). The Table 1 Effect of catalyst loading for the synthesis of 1,4-dihydropyridinesa Entry 1 2 3 4 5 6 7 8

Catalyst

Yieldb

(wt %)

Temperature (°C)

Time (min)

(%)

1 2.5 5 10 5 5

27 90 90 90 90 90 27 60

180 60 30 20 15 15 120 60

NRc 45 83 88 95 95 NRc 80

a Reaction conditions: benzaldehyde (2 mmol), ethyl acetoacetate (4 mmol) and ammonium carbonate (1.2 mmol). b Isolated yield. c No Reaction.

3 Table 2 The comparison dihydropyridinesa

of

ammonia

sources

for

the

synthesis

of

Entry

Ammonium salt

Temperature (°C)

Time (min)

Yieldb (%)

1

Ammonium carbonate Ammonium acetate Ammonium bicarbonate Ammonium chloride

90

15

95

90 90

15 15

85 80

90

15

40

2 3 4

1,4-

a Reaction conditions: benzaldehyde (2 mmol), ethyl acetoacetate (4 mmol) using different ammonia source at 90 °C solvent-free for 15 min. b Isolated yield.

catalyst was prepared from boric acid, a readily available, nontoxic, and inexpensive starting material. This catalyst is environmentally benign due to its mild acidity and non-toxic nature. We structured our study to investigate the suitability of sulfated polyborate as a catalyst for synthesis of 1,4dihydropyridines. For benzaldehyde (2 mmol), a representative substrate, ethyl acetoacetate (4 mmol) and ammonium carbonate (1.2 mmol) were used to afford Dimethyl 2,6-diethyl-4-phenyl1,4-dihydropyridine-3,5-dicarboxylate (Table 1 and 2). The product has a chiral center and the present method produces racemate which was confirmed by polarimetry. Effect of the catalyst loading on time and yields of the reaction was assessed (Table 1, entries 3-6). The reaction does not proceed in the absence of a catalyst at room temperature (Table 1, entry 1) while proceeded at 90 °C with low product yield (Table 1, entry 2). An increase of the catalyst loading increased the product yield with a reduction in reaction time (Table 1, entries 3-5). The catalyst loading beyond 5 wt % was

not advantageous (Table 1, entries 5 and 6), hence a 5 wt % catalyst loading was chosen for further study. Temperature played an important role in the synthesis of 1,4-dihydropyridines (Table 1, entry 7 and 8). The temperature effect was examined at ambient, 60 °C and 90 °C under the solvent free condition with sulfated polyborate as a catalyst. The reaction does not proceed at room temperature. Further increasing temperature to 90 °C resulted in increased product yield in shorter reaction time (Table 1, entries 5). Therefore, this was the optimum temperature for performing the reaction. We checked the e ect of the ammonium salts on the reaction yields, we scanned di erent ammonium salts with the 5 % loading of sulfated polyborate. The study revealed that ammonium carbonate was the reagent of choice. Thus, we studied a model four-component condensation of benzaldehyde, ethyl acetoacetate, and ammonium carbonate as nitrogen source under optimized conditions (Table 2). We were pleased to find Table 3 Comparison of the effect of the solvents for the synthesis of 1,4dihydropyridinesa Yieldb

Entry

Solvent

Temperature (°C)

Time (min)

(%)

1 2 3

Solvent free EtOH ACN

90 reflux reflux

15 60 60

95 55 Traces

4 5 6 7

THF H2O Toluene DMF

reflux reflux reflux 90

60 60 60 60

NRc 40 60 62

a Reaction conditions: benzaldehyde (2 mmol), ethyl acetoacetate (4 mmol) and ammonium carbonate (1.2 mmol). b Isolated yield. c No Reaction.

Table 4 Comparison of the efficiency of sulfated polyborate with literature reported acidic catalysts for the synthesis of 1,4-dihydropyridines. Entry

Catalyst

Reaction Condition

Time

Yield (%)

Ref.

1 2 3 4 5 6 7 8 9

Sulfated polyborate Silica gel sulphuric acid Nano-tungsten trioxide-supported Sulfonic acid (n-WSA) Silica sulfuric acid BF3-SiO2 nanoparticles Sulfated boric acid nanoparticles Nano-sulfated zirconia -Fe2O3@SiO2-SO3H p-TSA, strongly accelerated by ultrasonic irradiation

Solvent free/90 °C Solvent free/90 °C Solvent free/100 °C Solvent free/20 °C Solvent free/70 °C EtOH/60 °C EtOH/20 °C Solvent free/90 °C Aqueous micelles

15 min 15 min 16 min 20 min 20min 30 min 40 min 1h 1h

95 98a 98 96 91 96 92 98 96

This work 18 19 20 21 22 23 24 25

10 11 12 13 14

Cellulose sulfuric acid Uncatalyzed reaction Phenylboronic acid Silica gel/sulfonic acid catalyst (SiO2–SO3H) SiO2–NaHSO4

Solvent free/100 °C H2O/55-60 °C EtOH/reflux Solvent free/60 °C ACN/rt

2h 3.5 h 4h 5.5 h 6h

90 99 b 90 90 85

27 53 28 26 29

a

Extractive work up. b Ammonium carbonate as an ammonia source.

that among the conditions screened, the corresponding 1,4dihydropyridines was obtained quantitatively with ammonium carbonate at 90 °C. In addition to this ammonium carbonate is a less toxic (LD 50=1497mg/Kg), solid source of ammonia which is used in food products as a baking powder. The effect of various solvents in model reaction on time and yield of the reaction was ascertained (Table 3, entries 2-7). None of the solvents presented the advantage of time and yield over solvent free condition. Hence, the solvent free condition was regarded as best for the cost and environmental acceptability. In

all the experiments the products were isolated by aqueous quenching followed by filtration and washing the products with water. In comparison with literature reported other catalysts used for the synthesis of 1,4-dihydropyridines, sulfated polyborate catalyst showed an advantage with respect to reaction condition, workup procedure, time and yields (Table 4). To investigate the substrate scope, optimized reaction conditions were applied to substituted aromatic/aliphatic/α,βunsaturated aldehydes, and β-ketoesters. All the substrate variants reacted well and afforded high yields of the corresponding 1,4-

4 Tab ble 5 olvennt freee connditioon 64, a Sulfatted poolybooratee cataalyzeed synnthessis off 1,4-dihy ydroppyriddines undeer so O

R

H

R2

R2

+ R1

O

O

O

O O

R1

So olven nt free e, 90 0 oC Su ulfate ed Po olyborrate

R

O

R2

R2 R1

N H

R1

(NH O3 ( 4 )2 CO

a

β-Kettoestters β

Yieeldb (% %)

O Obs.

Liit.

15 2 25

95 92

157-1 1 158 1 160 159-1

15 58-16 6054 16 60-16 6254

O OCH H2CH H3

15

88

2 231 230-2

22 29-23 3055

CH H3 CH H3

O OCH H2CH H3 O OCH H2CH H3

15 2 25

93 92

160-1 1 161 1 145 144-1

16 62-16 6355 14 45-14 4855

4-C CH3-C C 6 H4

CH H3

O OCH H2CH H3

15

90

1 135 134-1

13 33-13 3455

4-O O2N-C C6 H 4 3-H HO-C C6 H 4 3-B Br-C6H4

CH H3 CH H3 CH H3

O OCH H2CH H3 O OCH H2CH H3 O OCH H2CH H3

15 2 25 2 20

91 86 89

130-1 1 132 1 189 188-1 1 115 113-1

13 32-13 34 18 85-18 8757 11 15-11758

10

3-C Cl-C6H4

CH H3

O OCH H2CH H3

2 20

88

1 139 138-1

14 40-14 42

11 12 13

3-O O2N-C C6 H 4 2-C CH3O-C O 6H4 2-H HO-C C6 H 4

CH H3 CH H3 CH H3

O OCH H2CH H3 O OCH H2CH H3 O OCH H2CH H3

30 3 4 40 4 40

90 85 85

163-1 1 164 1 158 157-1 1 118 117-1

16 65-16 6755 15 59-16 6059 12 21-12 23600

14 15

2-C Cl-C6H4 2-O O2N-C C6 H 4

CH H3 CH H3

O OCH H2CH H3 O H3 OCH

25 2 3 30

87 89

214-2 2 215 1 170 169-1

21 16-217 17 70-17 7261

16

H

CH H3

O OCH H2CH H3

15

89

1 166 164-1

16 65-16 6857

17

C3H7

CH H3

O OCH H2CH H3

2 20

87

1 122 121-1

12 20-12 2258

18

c-C C3H5

CH H3

O OCH H2CH H3

2 25

91

1 104 102-1

10 03-10 06

19 20

c-C C6H111 C6H5CH H=CH

CH H3 CH H3

O OCH H2CH H3 O OCH H2CH H3

35 3 2 20

90 86

113-1 1 114 1 148 146-1

11 13-11558 63 14 45-14 46

Entrry

Ald dehyd des (R)

R1

R R2

1 2

C6H5 4-C CH3O-C O 6H4

CH H3 CH H3

O OCH H2CH H3 O OCH H2CH H3

3

4-H HO-C C6 H 4

CH H3

4 5

4-B Br-C6H4 4-C Cl-C6H4

6 7 8 9

T e (m Time min)

M.P P. °C C

56

59

59

62

oacetaate (4 mmool) andd amm moniuum caarbonate (11.2 mm mol) at 90 °C soolvennt-freee for 15 R Reacti ion coonditiions: benza b aldehyyde (22 mm mol), ethyl e aceto 1 miin. b Issolateed yieeld.

veraal ddihyddroppyriddines withinn shhort reaaction time (Taable 5). Sev o o ellectrron--releeasinng or o ellectrron-w withhdraw wingg suubstiituennts at ortho an nd para p a poositioons of arom a maticc alddehyydess haave bbeenn exxamiinedd. T natuure oof substtituttion hass no siggnificcantt efffect on reacctionn The tiime andd yield y ds.64 Hoowevver, forr 2-meethoxxy and 2-hydrroxyy oducct su ubsttratees, tthe reac r ctionn tim me wass lonngerr wiith simiilar pro e y yieldd preesum mablyy duue too eleectroon reeleasingg efffectss (Taable 5, entry 12, 13). Thiss prootoccol was w alsoo appplicablee to alipphatiic alldehydess ( ble 5, 5 enntry 20)). Tablle 5, enntry 16-1 19) and cinnnam malddehydde (Tab (T on in i β-kettoestters wass O T On The otheer hand h d, methy m yl esster varriatio allso adap a ptable (T Tablle 5, enttry 15). prottocool to T This oleraates a vaarietty of o su ubstiituennts on o aarom maticc alldehhydees and a also appplicaable to alliphaatic//α,β--unssaturratedd alldehhydees allongg witth meth m hyl/eethyll estter varia v ants of β-keetoesterss mizedd fo or the t synntheesis of 1,44-dihhydrropyyridiines unnderr opptim co ondiitionns. portaant aattribbutee forr thee R clabbilityy off thee cattalysst is an imp Recy y off thee cattalyst in n thee in ndusstriaal suuitability y. Thhereeforee, reeusabbility m el reac mode r ctionn unde u er ooptim mizeed reaactioon conditioon wass e h reaactioon cy yclee, ev valuuatedd. Inn thiis sttudyy, aftter comp c pletion of each o Thee filttrate wass w r waas adddedd andd thee prooducct was water w filter f red off. or too reecovver cataalystt. ev vapoorateed in vvacu uum m rotaryy evvapoorato fouur ttimees with w h noo R overeed cataalystt w Reco was recyycleed for f siignifficannt looss in i caatalyytic aactivvity (Figg. 2)). d poolybboratte cataly yzedd T prop The p poseed mech m hanism for sulffated n in Schemee 2. The T first sy ynthhesiss of 1,4--dihy ydroopyrridinnes is shown sttep invvolvves sullfateed polyyborrate--cataalyzzed forrmattion of K evennagel prrodu Knoe uct I froom an equiivaleent of β-keetoester andd arrom matic or aliiphaatic aldeehydde. Thee neext stepp coompprises of

foormaationn of β-ennam minoeesterrs III froom thhe seconnd equiv e valent of o βkeetoesster and amm monnia (gen ( erated ‘in siitu’ from m am mmo onium

Figg. 2.. Reuusabiility oof thee cattalystt.

caarbonnatee). Mich M hael addi a itionn bettweeen unsat u turatted carb c bonyyl coompooundd I and a enam minee II,, followed by b prrotoon traansffers and finnallyy cyclizaationn gaave the t corre c espoonding 1,4-d 1 dihyydrop pyriidinee. Cooncllusioon Inn concluusionn, thhe pres p sent pro oceddure is an efficcien nt annd ecoe friienddly prottocool for f the syntheesis of 1,44-dihhydrropyyridiines thrrouggh one-p o pot reacctionn off varrious alddehyydess, β--keto oestters andd am mmoonium m carbo c onatte unde u er op ptim mal ccondditioons. Mild react r tion coondittions, shhortter react r tion tim me, high h her yield y d, ease of wor w rkup

5 and recyclability of the catalyst are the key features of this procedure. Moreover, this method also has the ability to tolerate a

wide variety of substituents.

Scheme 2. Proposed mechanism for sulfated polyborate catalyzed synthesis of 1,4-dihydropyridines.

Acknowledgements Authors are grateful to University Grants Commission, New Delhi, India for their financial support. References and notes 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

12. 13. 14. 15. 16. 17. 18.

Stout, D. M.; Meyers, A. I. Chem. Rev., 1982, 82, 223–243. Bossert, F.; Vater, W. Med. Res. Rev., 1989, 9, 291–324. Janis, R. Al.; Triggle, D.J. J. Med. Chem., 1983, 26, 775–785. Boecker, R. H.; Guengerich, F. P. J. Med. Chem., 1986, 29, 1596–1603. Sausins, A.; Duburs, G. Heterocycl., 1988, 27, 269–289. Godfraind, T.; Miller, R.; Wibo, M. Pharmacol. Rev., 1986, 38, 321– 416. Mager, P. P.; Coburn, R. A.; Solo, A. J.; Triggle, D. J.; Rothe, H. Drug Des. Discov., 1992, 8, 273–289. Stilo, A. Di.; Visentin, S.; Cena, C.; Gasco, A. M.; Ermondi, G.; Gasco, A. J. Med. Chem., 1998, 41, 5393–5401. Bossert, F.; Meyer, H.; Wehinger, E. Angew. Chem. Int. Ed. Engl., 1981, 20, 762–769. Nakayama, H.; Kanaoka, Y. Heterocycl. 1996, 42, 901-909. Sunkel, C. E.; Fau de Casa-Juana, M.; Santos, L.; Garcia, A. G.; Artalejo, C. R.; Villarroya, M.; Gonzalez-Morales, M. A.; Lopez, M. G.; Cillero, J. J. Med. Chem., 1992, 35, 2407–2414. Cooper, K.; Fray, M. J.; Parry, M. J.; Richardson, K.; Steele, J. J. Med. Chem., 1992, 35, 3115-3129. Lavilla, R. J. Chem. Soc., Perkin Trans. 2002, 1, 1141-1156. Comins, D. L.; O’Connor, S. Adv. Heterocycl. Chem., 1988, 44, 199– 267. Hantzsch, A. Justus Liebigs Ann. Chem., 1882, 215, 1-82. Maheswara, M.; Siddaiah, V.; Rao, Y. K.; Tzeng, Y.-M.; Sridhar, C. J. Mol. Catal. A: Chem., 2006, 260, 179-180. Sharma, G. V. M.; Reddy, K. L.; Lakshmi, P. S.; Krishna, P. R. Synth., 2006, 2006, 55-58. Kolvari, E.; Zolfigol, M.; Koukabi, N.; Shirmardi-Shaghasemi, B. Chem. Pap., 2011, 65, 898-902.

19. Bitaraf, M.; Amoozadeh, A.; Otokesh, S. J. Chin. Chem. Soc., 2016, 63, 336–344. 20. Datta, B.; Pasha, M. A. Chin. J. Catal., 2011, 32, 1180-1184. 21. Sadeghi, B.; Namakkoubi, A.; Hassanabadi, A. J. Chem. Res., 2013, 37, 11-13. 22. Azizi, K.; Azarnia, J.; Karimi, M.; Yazdani, E.; Heydari, A. Synlett, 2016. 23. Teimouri, A.; Ghorbanian, L.; Moatari, A. Bull. Chem. Soc. Ethiop., 2013, 27, 427-437. 24. Koukabi, N.; Kolvari, E.; Zolfigol, M. A.; Khazaei, A.; Shaghasemi, B. S.; Fasahati, B. Adv. Synth. Catal., 2012, 354, 2001–2008. 25. Kumar, A.; Maurya, R. A. Synlett, 2008, 2008, 883-885. 26. Gupta, R.; Gupta, R.; Paul, S.; Loupy, A. Synthesis, 2007, 2007, 28352838. 27. Murthy, Y. L. N.; Rajack, A.; Ramji, M.T.; Praveen, C.; Lakshmi, K. A. Bioorg. Med. Chem. Lett., 2012, 22, 6016-6023. 28. Debache, A.; Boulcina, R.; Belfaitah, A.; Rhouati, S.; Carboni, B. Synlett, 2008, 2008, 509-512. 29. Chari, M. A.; Syamasundar, K. Catal. Commun., 2005, 6, 624-626. 30. Pei, W.; Wang, Q.; Li, X.; Sun, L. Chin. J. Chem., 2010, 28, 483–486. 31. Das Sharma, S.; Hazarika, P.; Konwar, D. Catal. Commun., 2008, 9, 709-714. 32. Sabitha, G.; Arundhathi, K.; Sudhakar, K.; Sastry, B. S.; Yadav, J. S. Synth. Commun., 2009, 39, 2843-2851. 33. Donelson, J. L.; Gibbs, R. A.; De, S. K. J. Mol. Catal. A: Chem., 2006, 256, 309-311. 34. Sabitha, G.; Reddy, G.S.K.K.; Reddy, C. S.; Yadav, J. S. Tetrahedron Lett., 2003, 44, 4129-4131. 35. Das, B.; Ravikanth, B.; Ramu, R.; Vittal Rao, B. Chem. Pharm. Bull., 2006, 54, 1044-1045. 36. Zonouz, A. M.; Hosseini, S. B.; Synth. Commun., 2008, 38, 290-296. 37. Adibi, H.; Samimi, H. A.; Beygzadeh, M. Catal. Commun., 2007, 8, 2119-2124. 38. Heravi, M. M.; Bakhtiari, K.; Javadi, N. M.; Bamoharram, F. F.; Saeedi, M.; Oskooie, H. A. J. Mol. Catal. A: Chem., 2007, 264, 50-52. 39. Debache, A.; Ghalem, W.; Boulcina, R.; Belfaitah, A.; Rhouati, S.;

6 Carboni, B. Tetrahedron Lett., 2009, 50, 5248-5250. 40. Salehi, H.; Guo, Q. Synth. Commun., 2004, 34, 4349-4357. 41. Akbari, J. D.; Tala, S. D.; Dhaduk, M. F.; Joshi, H. S. Arkivoc, 2008, 12, 126-135. 42. Sridhar, R.; Perumal, P. T. Tetrahedron, 2005, 61, 2465-2470. 43. Lee, J. H. Tetrahedron Lett., 2005, 46, 7329-7330. 44. Wang, S.-X.; Li, Z.-Y.; Zhang, J.-C.; Li, J.-T. Ultrason. Sonochem., 2008, 15, 677-680. 45. Yadav, J. S.; Reddy, B. V Subba; Reddy, P. T. Synth. Commun., 2001, 31, 425-430. 46. Kawase, M.; Shah, A.; Gaveriya, H.; Motohashi, N.; Sakagami, Varga, A.; Molnár, J. Bioorg. Med. Chem., 2002, 10, 1051-1055. 47. Shahrisa, A.; Esmati, S.; Nazari, M. G.; J. Chem. Sci., 2012, 124, 927931. 48. Arce, G.; Carrau, G.; Bellomo, A.; Gonzalez, D. World J. Chem. Edu., 2015, 3, 27-29. 49. Chandrasekhar, S.; Gopalaiah, K. Tetrahedron Lett., 2002, 43, 24552457. 50. Khatri, C. K.; Rekunge, D. S.; Chaturbhuj, G. U. New J. Chem., 2016, 40, 10412-10417. 51. Khatri, C. K.; Satalkar, V. B.; Chaturbhuj, G. U. Tetrahedron Lett. 2017, 58, 694-698. 52. Indalkar, K. S.; Khatri, C. K.; Chaturbhuj, G. U. J. Chem. Sci. 2017, 129, 141–148. 53. Tamaddon, F.; Razmi, Z.; Jafari, A. A. Tetrahedron Lett., 2010, 51, 1187-1189. 54. Naik, T. R. R.; Shivashankar, S. A. Tetrahedron Lett., 2016, 57, 40464049. 55. Wang, P.; Wang, J.; Au, C.; Qiu, R.; Xu, X.; Yin, S. Adv. Synth. Catal., 2016, 358, 1302-1308. 56. Srinivasan, V. V.; Ranoux, A.; Maheswari, R.; Hanefeld, U.; Ramanathan, A.; Subramaniam, B. Res. Chem. Intermed., 2016, 42, 2399-2408. 57. Alvim, H. G. O.; Bataglion, G. A.; Ramos, L. M.; Oliveira, A.L. de; Oliveira, H.C.B. de; Eberlin, M. N.; Macedo, J. L. de; Silva, W. A. da; Neto, B.A.D. Tetrahedron, 2014, 70, 3306-3313. 58. Chang, C.-C.; Cao, S.; Kang, S.; Kai, L.; Tian, X.; Pandey, P.; Dunne, S. F.; Luan, C.-H; Surmeier, D. J.; Silverman, R. B. Bioorg. Med. Chem., 2010, 18, 3147-3158. 59. Alinezhad, H.; Tavakkoli, S. M. Res. Chem. Intermed., 2015, 41, 59315940. 60. Montazeri, N.; Pourshamsian, K.; Zoghi, R.; Mahjoob, S. Orient. J. Chem., 2012, 28, 103. 61. Wu, X. Y. Synth. Commun., 2012, 42, 454-459. 62. Bridgwood, K. L.; Veitch, G. E.; Ley, S. V. Org. lett., 2008, 10, 36273629. 63. Safari, J.; Azizi, F.; Sadeghi, M. New J. Chem., 2015, 39, 1905-1909. 64. General procedure for the synthesis of 1,4-dihydropyridines: A mixture of β-ketoester (4 mmol), aldehyde (2 mmol), ammonium carbonate (1.2 mmol) and sulfated polyborate (5 wt %) was heated at 90 °C. The reaction was monitored by thin layer chromatography. After completion of the reaction, reaction mixture was cooled to room temperature and quenched by water; solid precipitated was filtered at vacuum pump, washed with water (3 X 5 mL), dried under vacuum and recrystallized from ethanol to afford the pure product.

*Highlights

Highlights: 

Simple, and efficient method for preparation of 1,4-dihydropyridines.



Less toxic ammonium carbonate used as an ammonia source.



Recyclable catalyst with no significant loss in activity.



Protocol tolerates a variety of substituents on aromatic and aliphatic aldehydes.