Hindawi Publishing CorporationJournal of ChemistryVolume 2013 Article ID 495982 6 pageshttpdxdoiorg1011552013495982
Research ArticleSynthesis of 14-Dihydropyridines Bearing a CarbamateMoiety on the 4-Position
Davood Habibi Mohammad Ali Zolfigol and Maliheh Safaee
Department of Organic Chemistry Faculty of Chemistry Bu-Ali Sina University Hamedan 6517838683 Iran
Correspondence should be addressed to Davood Habibi davoodhabibigmailcom
Received 20 May 2013 Accepted 8 July 2013
Academic Editor Augusto C Tome
Copyright copy 2013 Davood Habibi et alThis is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
A good range of 14-dihydropyridines bearing a carbamate moiety on the 4-position were synthesized from the primary reactionof different hydroxyaldehydes with phenyl isocyanates and the subsequent reaction of the obtained carbamates with methylacetoacetate in the presence of ammonium fluoride When phenyl isothiocyanate was used in place of phenyl isocyanate in thesame condition the reaction did not take place
1 Introduction
14-Dihydropyridines and their derivatives have gained con-siderable importance in the field of organic and medicinalchemistry since they have fascinating pharmacological prop-erties [1ndash9] The 14-dihydropyridine skeleton is common inmany to be useful as calcium channel blockers [10 11] andthey are used most frequently as drugs such as nifedipinenicardipine and amlodipine which have been found ascardiovascular agents for the treatment of hypertension [12]Moreover studies have discovered that 14-dihydropyridinesexhibit diverse medical functions such as neuroprotectantsplatelet antiaggregators and chemosensitizers and are impor-tant in Alzheimerrsquos disease as anti ischaemic agents [13 14]However preparation of new type of 14-dihydropyridinesis an active ongoing research area and there is scope forfurther improvement toward milder reaction conditions andimproved yields We demonstrated that the ammoniumsalt could be replaced with ammonia [15] A number ofimproved methods have been reported in the literature forthis condensation which involve the use of microwave ionicliquids reflux high temperature AlCl
silica gelsulfonic acid [27] PTSSA [28] montmorilloniteK10 clay [29] and phenylboronic acid [30] Additionallydihydropyridines are often produced in a synthetic sequenceand have to be oxidized to pyridines [31]
The most interesting aspect of dihydropyridines can beattributed to the coenzyme reduced nicotinamide adeninedinucleotide (NADH) and the unique ability of these com-pounds in biological systems to reduce unsaturated function-alities and also strained ring systems (carbonyls conjugatedolefins epoxides etc) [32] Although 14-dihydropyridineswith various aromatic heteroaromatic [33] aliphatic andsugar [34] substituents at C4 have been reported there is noreport of 14-dihydropyridines bearing carbamate substituentat C4
2 Result and Discussion
We decided to develop the chemistry of this class of com-pounds and also provide a clean and easy work-up proce-dure In continuation of our researches on the synthesis ofheterocycles [35ndash41] we herein report a good range of 14-dihydropyridines which have a carbamate moiety on the 4-position They were synthesized from a primary reactionof different hydroxyaldehydes with phenyl isocyanates andthe subsequent reaction of the obtained carbamates withmethyl acetoacetate in the presence of ammonium fluoride
2 Journal of Chemistry
HN C
RO
O
N CR
O + HOR998400
R998400
CHO CHOSolvent free
70∘C
1andashf
Scheme 1 Preparation of different carbamates from phenyl isocyanates and aldehydes
Table 1 Synthesis of various carbamate derivatives (1andashf)
Entry Phenyl isocyanate Aldehyde Carbamate Time (min) Yielda Mp ∘C
1 N C O HO CHO CHOHN C
OO
1a20 92 129ndash133
2 N C OHO
CHO
CHOHN C
OO
1b15 96 160ndash164
3 N C OHO CHO
OMeCHO
OMe
HN C
OO
1c210 64b 125ndash129
4 N C OHO CHO
OEtCHO
OEt
HN C
OO
1d210 93b 106ndash110
5 N C O
Cl
Cl HO CHO CHOHN C
OO
Cl
Cl1e 195 78b 187ndash191
6 N C O
Cl
Cl
HO
CHO
CHOHN C
OOCl
Cl1f
195 70b 191ndash194
aIsolated yieldbReaction took place in ethyl acetate
(Scheme 1 and Table 1) The obtained carbamates (R10158401015840CHO1andashf) will then react with methyl acetoacetate in the presenceof ammonium fluoride to give different 14-dihydropyridines(2andashf Scheme 2 and Table 2)
When phenyl isothiocyanate was used instead of phenylisocyanate in the same condition the reaction did not takeplace Also when ammonium carbonate was used insteadof ammonium fluoride the dihydropyridine which containsphenolic group at 4-position and phenylcarbamic acid wereobtained So dimethyl 26-dimethyl-4-(4-(phenylcarbamoy-loxy)phenyl)-14-dihydropyridine-35-dicarboxylate (2a) willbe hydrolyzed to dimethyl 4-(4-hydroxy-phenyl)-26-dime-thyl-14-dihydro-pyridine-35-dicarboxylate (3a mp 224ndash226∘C) and phenylcarbamic acid in the presence of ammo-nium carbonate (Scheme 3) Apparently the released waterfrom ammonium carbonate hydrolyzes the carbamate part ofthe dihydropyridines
All compounds were characterized by 1H NMR and IRIn the 1H NMR spectrum of the 14-dihydropyridines apeak at 43ndash492 ppm belongs to the proton at C-4 positionIn the IR spectrum a strong absorbance peak for the NndashH group of the corresponding 14-dihydropyridines appears
at 3277ndash3336 cmminus1 (Figure 1 see Supporting Informationavailable online at httpdxdoiorg1011552013495982)
3 Experimental
All reagents were purchased from the Merck and Aldrichchemical companies and used without further purificationProducts were characterized by spectroscopy data (FT-IR 1HNMR spectra) The NMR spectra were recorded in CDCl
3
acetone and DMSO 1H NMR spectra were recorded ona Bruker Avance DRX 90MHz instrument The chemicalshifts (120575) are reported in ppm relative to the TMS as internalstandard FT-IR (KBr) spectra were recorded on a Perkin-Elmer 781 spectrophotometer Melting points were takenin open capillary tubes with a BUCHI 510 melting pointapparatus and were uncorrected The elemental analysis wasperformed using Heraeus CHN-O-Rapid analyzer TLC wasperformed on silica gel polygram SIL GUV 254 plates
31 General Procedure for the Synthesis of Carbamates (1andashf) Amixture of hydroxybenzaldehydes (10mM) and phenylisocyanate derivatives (10mM) was stirred in ethyl acetate or
Journal of Chemistry 3
O ON
H
H
2
80∘C
OCH3
R998400998400CHO
+
H3C
NH4FH3COOC
R998400998400
COOCH3
CH3H3C
2andashf
(1andashf)
Scheme 2 Preparation of different 14-dihydropyridines from carbamates and methyl acetoacetate
NH
O
O
NH
NH
O
NH
(NH4)2CO3 2NH3 + H2CO3
H2CO3
HeatCO2 + H2O
H2OH3COOC H3COOCCOOCH3 COOCH3
H3C H3CCH3 CH3
OH + HO
3a2a
Scheme 3 Hydrolysis of 2a
NH
H
OO
NH
H3COOC COOCH3
CH3H3C
1151110105100
959085807570656055504540353025201510
3540000 3000 2000 1500 1000 5500
(cmminus1)
T(
)
Figure 1 IR spectrum of dimethyl 26-dimethyl-4-(4-(phenylcarbamoyloxy)phenyl)-14-dihydropyridine-35-dicarboxylate (2a)
4 Journal of Chemistry
Table 2 Synthesis of 14-dihydropyridine derivatives (2andashf)
Entry Carbamates Product Yielda Time (h) Mp ∘C
1HN C
O
O CHO1a
NH
O
ONH
H3COOC COOCH3
CH3H3C
2a88 17 240ndash243
2
CHOHN C
O
O1b
NH
OO
NH
H3COOC COOCH3
CH3H3C
2b91 24 233ndash238
3 CHOHN C
O
O
OMe1c
NH
O
O
NH
MeOH3COOC COOCH3
CH3H3C
2c75 24 228ndash234
4 CHO
OEt
HN C
O
O
1d
NH
O
ONH
EtOH3COOC COOCH3
CH3H3C
2d53 24 225ndash230
5 CHOHN C
O
OCl
Cl 1e
Cl
Cl
NH
OO
NH
H3COOC COOCH3
CH3H3C
2e 70 20 242ndash248
6
CHO
Cl
Cl
HN C
O
O
1f
Cl
Cl
NH
OO
NH
COOCH3
CH3
H3COOC
H3C
2f 69 20 232ndash244
aIsolated yield
solvent-free at 70∘C in an appropriate time and progress ofthe reaction wasmonitored by TLC (Scheme 1 Table 1) Aftercompletion the suspension was cooled ethyl acetate evap-orated the solid was crystallized in ethanol to get the purecarbamates and the obtained crystals were characterized by1H NMR and IR
32 Typical Procedure for the Synthesis of 14-Dihydropyridines(2andashf) A mixture of carbamate (10mM) methyl acetoac-etate (20mM) and ammonium fluoride (20mM) wasstirred in ethyl acetate at 80∘C for appropriate time andprogress of the reaction was monitored by TLC (Scheme 2Table 2) After completion the suspension was cooled ethyl
Journal of Chemistry 5
acetate evaporated and ethanol was added to dissolve anyimpurities since the 14-dihydropyridines donot dissolve inethanolThe obtained solid was pure and characterized by 1HNMR and IR
4 Conclusions
We demonstrated the synthesis of a good range of 14-dihydropyridines which have a carbamate moiety on the 4-position from the primary reaction of different aldehydeswith phenyl isocyanate and the subsequent reaction of theobtained carbamateswithmethyl acetoacetate in the presenceof ammonium fluoride As stated before when phenyl isoth-iocyanate was used instead of phenyl isocyanate in the samecondition the reactions did not take place
Disclosure
Theauthors of the paper do not have a direct financial relationwith the commercial identities mentioned in this paper
Acknowledgment
The authors gratefully acknowledge the financial supportfrom the Bu-Ali Sina University Hamedan Iran
References
[1] A R Trivedi D K Dodiya B H Dholariya V B Kataria VR Bhuva and V H Shah ldquoSynthesis and biological evaluationof some novel N-aryl-14- dihydropyridines as potential anti-tubercular agentsrdquo Bioorganic and Medicinal Chemistry Lettersvol 21 no 18 pp 5181ndash5183 2011
[2] V P Pandey S S BishtMMishra et al ldquoSynthesis andmolecu-lar docking studies of 1-phenyl-4-glycosyl-dihydropyridines aspotent antileishmanial agentsrdquo European Journal of MedicinalChemistry vol 45 no 6 pp 2381ndash2388 2010
[3] K Sirisha D Bikshapathi G Achaiah and V M ReddyldquoSynthesis antibacterial and antimycobacterial activities ofsomenew4-arylheteroaryl-26-dimethyl-35-bis-N-(aryl)-car-bamoyl-14-dihydropyridinesrdquo European Journal of MedicinalChemistry vol 46 no 5 pp 1564ndash1571 2011
[4] K Sirisha M C Shekhar K Umasankar et al ldquoMoleculardocking studies and in vitro screening of new dihydropyridinederivatives as human MRP1 inhibitorsrdquo Bioorganic and Medici-nal Chemistry vol 19 no 10 pp 3249ndash3254 2011
[5] M Kawase A Shah H Gaveriya et al ldquo35-Dibenzoyl-14-dihydropyridines synthesis and MDR reversal in tumor cellsrdquoBioorganic andMedicinal Chemistry vol 10 no 4 pp 1051ndash10552002
[6] M Suarez Y Verdecia B Illescas et al ldquoSynthesis and studyof novel fulleropyrrolidines bearing biologically active 14-dihydropyridinesrdquo Tetrahedron vol 59 no 46 pp 9179ndash91862003
[7] R Shan C Velazquez and E E Knaus ldquoSyntheses cal-cium channel agonist-antagonist modulation activities andnitric oxide release studies of nitrooxyalkyl 14-dihydro-26-dimethyl-3-nitro-4-(213-benzoxadiazol-4-yl) pyridine-5-carboxylate racemates enantiomers and diastereomersrdquo Jour-nal of Medicinal Chemistry vol 47 no 1 pp 254ndash261 2004
[8] N I Ryabokon R I Goncharova G Duburs and J Rzeszo-wska-Wolny ldquoA 14-dihydropyridine derivative reduces DNAdamage and stimulates DNA repair in human cells in vitrordquoMutation Research vol 587 no 1-2 pp 52ndash58 2005
[9] T Yamamoto S Niwa S Ohno et al ldquoStructure-activityrelationship study of 14-dihydropyridine derivatives blockingN-type calcium channelsrdquo Bioorganic and Medicinal ChemistryLetters vol 16 no 4 pp 798ndash802 2006
[10] R A Janis and D J Triggle ldquoNew developments in calcium ionchannel antagonistsrdquo Journal of Medicinal Chemistry vol 26pp 775ndash785 1983
[11] R H Bocker and F P Guengerich ldquoOxidation of 4-aryl-and 4-alkyl-substituted 26-dimethyl-35-bis(alkoxycarbonyl)-14-dihydropyridines by human livermicrosomes and immuno-chemical evidence for the involvement of a form of cytochromeP-450rdquo Journal of Medicinal Chemistry vol 29 no 9 pp 1596ndash1603 1986
[12] F R Buhler andW Kiowski ldquoCalcium antagonists in hyperten-sionrdquo Journal of Hypertension vol 5 no 3 pp s3ndashs10 1987
[13] V Klusa ldquoCerebrocrast Neuroprotectant cognition enhancerrdquoDrugs of the Future vol 20 no 2 pp 135ndash138 1995
[14] R G Bretzel C C Bollen E Maeser and K F FederlinldquoNephroprotective effects of nitrendipine in hypertensive typeI and type II diabetic patientsrdquo American Journal of KidneyDiseases vol 21 no 6 pp 53ndash64 1993
[15] M A Zolfigol and M Safaiee ldquoSynthesis of 14-dihydropyridi-nes under solvent-free conditionsrdquo Synlett no 5 pp 827ndash8282004
[16] S Das Sharma P Hazarika and D Konwar ldquoA simple greenand one-pot four-component synthesis of 14-dihydropyridinesand their aromatizationrdquo Catalysis Communications vol 9 no5 pp 709ndash714 2008
[17] S-X Wang Z-Y Li J-C Zhang and J-T Li ldquoThe solvent-freesynthesis of 14-dihydropyridines under ultrasound irradiationwithout catalystrdquo Ultrasonics Sonochemistry vol 15 no 5 pp677ndash680 2008
[18] N Tewari N Dwivedi and R P Tripathi ldquoTetrabutylam-monium hydrogen sulfate catalyzed eco-friendly and efficientsynthesis of glycosyl 14-dihydropyridinesrdquo Tetrahedron Lettersvol 45 no 49 pp 9011ndash9014 2004
[19] G V M Sharma K L Reddy P S Lakshmi and P R KrishnaldquoldquoIn siturdquo generated ldquoHClrdquomdashan efficient catalyst for solvent-free Hantzsch reaction at room temperature synthesis of newdihydropyridine glycoconjugatesrdquo Synthesis no 1 Article IDP05205SS pp 55ndash58 2006
[20] S Ko M N V Sastry C Lin and C-F Yao ldquoMolecular iodine-catalyzed one-pot synthesis of 4-substituted-14- dihydropyri-dine derivatives viaHantzsch reactionrdquoTetrahedron Letters vol46 no 34 pp 5771ndash5774 2005
[21] M Adharvana Chari and K Syamasundar ldquoSilica gelNaHSo4
[22] G Sabitha G S K K Reddy C S Reddy and J SYadav ldquoA novel TMSI-mediated synthesis of Hantzsch 14-dihydropyridines at ambient temperaturerdquo Tetrahedron Lettersvol 44 no 21 pp 4129ndash4131 2003
[23] S Kikuchi M Iwai H Murayama and S-I FukuzawaldquoCatalytic synthesis of 14-dihydropyridine derivatives usingscandium(III) triflaterdquo Tetrahedron Letters vol 49 no 1 pp114ndash116 2008
6 Journal of Chemistry
[24] V Sridharan P T Perumal C Avendano and J C MenendezldquoA new three-component domino synthesis of 14-dihydro-pyridinesrdquo Tetrahedron vol 63 no 21 pp 4407ndash4413 2007
[25] H Adibi H A Samimi and M Beygzadeh ldquoIron(III) trifluo-roacetate and trifluoromethanesulfonate recyclable Lewis acidcatalysts for one-pot synthesis of 34-dihydropyrimidinones ortheir sulfur analogues and 14-dihydropyridines via solvent-free Biginelli and Hantzsch condensation protocolsrdquo CatalysisCommunications vol 8 no 12 pp 2119ndash2124 2007
[26] A Kumar and R A Maurya ldquoOrganocatalysed three-com-ponent domino synthesis of 14-dihydropyridines under solventfree conditionsrdquo Tetrahedron vol 64 no 16 pp 3477ndash34822008
[27] R Gupta R Gupta S Paul andA Loupy ldquoCovalently anchoredsulfonic acid on silica gel as an efficient and reusable hetero-geneous catalyst for the one-pot synthesis of Hantzsch 14-dihydropyridines under solvent-free conditionsrdquo Synthesis no18 pp 2835ndash2838 2007
[28] A Kumar and R A Maurya ldquoEfficient synthesis of Hantzschesters and polyhydroquinoline derivatives in aqueous micellesrdquoSynlett no 6 pp 883ndash885 2008
[29] AM Zonouz and S B Hosseini ldquoMontmorillonite K10 clay anefficient catalyst for Hantzsch synthesis of 14-dihydropyridinederivativesrdquo Synthetic Communications vol 38 no 2 pp 290ndash296 2008
[30] A Debache R Boulcina A Belfaitah S Rhouati and BCarboni ldquoOne-pot synthesis of 14-dihydropyridines via aphenylboronic acid catalyzed Hantzsch three-component reac-tionrdquo Synlett no 4 pp 509ndash512 2008
[31] M M Heravi F K Behbahani H A Oskooie and R H ShoarldquoCatalytic aromatization of Hantzsch 14-dihydropyridines byferric perchlorate in acetic acidrdquoTetrahedron Letters vol 46 no16 pp 2775ndash2777 2005
[32] H R Memarian and A Mirjafari ldquoSolid state photochemistryof 14-dihydropyridinesrdquo Bioorganic and Medicinal ChemistryLetters vol 15 no 14 pp 3423ndash3425 2005
[33] A Zarghi H Sadeghi A Fassihi M Faizi and A Shafiee ldquoSyn-thesis and calcium antagonist activity of 14-dihydropyridinescontaining phenylaminoimidazolyl substituentsrdquo Farmaco vol58 no 11 pp 1077ndash1081 2003
[34] A Dondoni A Massi and E Minghini ldquoTwo- andthree-component Hantzsch reaction using C-glycosylatedreagents Approach to the asymmetric synthesis of 14-diyhydropyridinesrdquo Synlett no 1 pp 89ndash92 2002
[35] MNasrollahzadeh Y Bayat DHabibi and SMoshaee ldquoFeCl3-
SiO2as a reusable heterogeneous catalyst for the synthesis of
5-substituted 1H-tetrazoles via [2+3] cycloaddition of nitrilesand sodium aziderdquoTetrahedron Letters vol 50 no 31 pp 4435ndash4438 2009
[36] D Habibi M Nasrollahzadeh A R Faraji and Y Bayat ldquoEffi-cient synthesis of arylaminotetrazoles in waterrdquo Tetrahedronvol 66 no 21 pp 3866ndash3870 2010
[37] M Nasrollahzadeh D Habibi Z Shahkarami and Y BayatldquoA general synthetic method for the formation of arylaminote-trazoles using natural natrolite zeolite as a new and reusableheterogeneous catalystrdquo Tetrahedron vol 65 no 51 pp 10715ndash10719 2009
catalyst for the preparation of arylaminotetrazolesrdquo SyntheticCommunications vol 40 no 21 pp 3159ndash3167 2010
[39] D Habibi and M Nasrollahzadeh ldquoSynthesis of arylaminote-trazoles by ZnCl
2AlCl
3silica as an efficient heterogeneous
catalystrdquo Monatshefte fur Chemie vol 143 no 6 pp 925ndash9302012
[40] DHabibiMNasrollahzadeh and T A Kamali ldquoGreen synthe-sis of the 1-substituted 1H-1234-tetrazoles by application of theNatrolite zeolite as a new and reusable heterogeneous catalystrdquoGreen Chemistry vol 13 no 12 pp 3499ndash3504 2011
[41] D Habibi and M Nasrollahzadeh ldquoZnO as an effectiveand reusable heterogeneous catalyst for the synthesis ofary-laminotetrazolesrdquo Synthetic Communications vol 42 pp 2023ndash2032 2012
Scheme 1 Preparation of different carbamates from phenyl isocyanates and aldehydes
Table 1 Synthesis of various carbamate derivatives (1andashf)
Entry Phenyl isocyanate Aldehyde Carbamate Time (min) Yielda Mp ∘C
1 N C O HO CHO CHOHN C
OO
1a20 92 129ndash133
2 N C OHO
CHO
CHOHN C
OO
1b15 96 160ndash164
3 N C OHO CHO
OMeCHO
OMe
HN C
OO
1c210 64b 125ndash129
4 N C OHO CHO
OEtCHO
OEt
HN C
OO
1d210 93b 106ndash110
5 N C O
Cl
Cl HO CHO CHOHN C
OO
Cl
Cl1e 195 78b 187ndash191
6 N C O
Cl
Cl
HO
CHO
CHOHN C
OOCl
Cl1f
195 70b 191ndash194
aIsolated yieldbReaction took place in ethyl acetate
(Scheme 1 and Table 1) The obtained carbamates (R10158401015840CHO1andashf) will then react with methyl acetoacetate in the presenceof ammonium fluoride to give different 14-dihydropyridines(2andashf Scheme 2 and Table 2)
When phenyl isothiocyanate was used instead of phenylisocyanate in the same condition the reaction did not takeplace Also when ammonium carbonate was used insteadof ammonium fluoride the dihydropyridine which containsphenolic group at 4-position and phenylcarbamic acid wereobtained So dimethyl 26-dimethyl-4-(4-(phenylcarbamoy-loxy)phenyl)-14-dihydropyridine-35-dicarboxylate (2a) willbe hydrolyzed to dimethyl 4-(4-hydroxy-phenyl)-26-dime-thyl-14-dihydro-pyridine-35-dicarboxylate (3a mp 224ndash226∘C) and phenylcarbamic acid in the presence of ammo-nium carbonate (Scheme 3) Apparently the released waterfrom ammonium carbonate hydrolyzes the carbamate part ofthe dihydropyridines
All compounds were characterized by 1H NMR and IRIn the 1H NMR spectrum of the 14-dihydropyridines apeak at 43ndash492 ppm belongs to the proton at C-4 positionIn the IR spectrum a strong absorbance peak for the NndashH group of the corresponding 14-dihydropyridines appears
at 3277ndash3336 cmminus1 (Figure 1 see Supporting Informationavailable online at httpdxdoiorg1011552013495982)
3 Experimental
All reagents were purchased from the Merck and Aldrichchemical companies and used without further purificationProducts were characterized by spectroscopy data (FT-IR 1HNMR spectra) The NMR spectra were recorded in CDCl
3
acetone and DMSO 1H NMR spectra were recorded ona Bruker Avance DRX 90MHz instrument The chemicalshifts (120575) are reported in ppm relative to the TMS as internalstandard FT-IR (KBr) spectra were recorded on a Perkin-Elmer 781 spectrophotometer Melting points were takenin open capillary tubes with a BUCHI 510 melting pointapparatus and were uncorrected The elemental analysis wasperformed using Heraeus CHN-O-Rapid analyzer TLC wasperformed on silica gel polygram SIL GUV 254 plates
31 General Procedure for the Synthesis of Carbamates (1andashf) Amixture of hydroxybenzaldehydes (10mM) and phenylisocyanate derivatives (10mM) was stirred in ethyl acetate or
Journal of Chemistry 3
O ON
H
H
2
80∘C
OCH3
R998400998400CHO
+
H3C
NH4FH3COOC
R998400998400
COOCH3
CH3H3C
2andashf
(1andashf)
Scheme 2 Preparation of different 14-dihydropyridines from carbamates and methyl acetoacetate
NH
O
O
NH
NH
O
NH
(NH4)2CO3 2NH3 + H2CO3
H2CO3
HeatCO2 + H2O
H2OH3COOC H3COOCCOOCH3 COOCH3
H3C H3CCH3 CH3
OH + HO
3a2a
Scheme 3 Hydrolysis of 2a
NH
H
OO
NH
H3COOC COOCH3
CH3H3C
1151110105100
959085807570656055504540353025201510
3540000 3000 2000 1500 1000 5500
(cmminus1)
T(
)
Figure 1 IR spectrum of dimethyl 26-dimethyl-4-(4-(phenylcarbamoyloxy)phenyl)-14-dihydropyridine-35-dicarboxylate (2a)
4 Journal of Chemistry
Table 2 Synthesis of 14-dihydropyridine derivatives (2andashf)
Entry Carbamates Product Yielda Time (h) Mp ∘C
1HN C
O
O CHO1a
NH
O
ONH
H3COOC COOCH3
CH3H3C
2a88 17 240ndash243
2
CHOHN C
O
O1b
NH
OO
NH
H3COOC COOCH3
CH3H3C
2b91 24 233ndash238
3 CHOHN C
O
O
OMe1c
NH
O
O
NH
MeOH3COOC COOCH3
CH3H3C
2c75 24 228ndash234
4 CHO
OEt
HN C
O
O
1d
NH
O
ONH
EtOH3COOC COOCH3
CH3H3C
2d53 24 225ndash230
5 CHOHN C
O
OCl
Cl 1e
Cl
Cl
NH
OO
NH
H3COOC COOCH3
CH3H3C
2e 70 20 242ndash248
6
CHO
Cl
Cl
HN C
O
O
1f
Cl
Cl
NH
OO
NH
COOCH3
CH3
H3COOC
H3C
2f 69 20 232ndash244
aIsolated yield
solvent-free at 70∘C in an appropriate time and progress ofthe reaction wasmonitored by TLC (Scheme 1 Table 1) Aftercompletion the suspension was cooled ethyl acetate evap-orated the solid was crystallized in ethanol to get the purecarbamates and the obtained crystals were characterized by1H NMR and IR
32 Typical Procedure for the Synthesis of 14-Dihydropyridines(2andashf) A mixture of carbamate (10mM) methyl acetoac-etate (20mM) and ammonium fluoride (20mM) wasstirred in ethyl acetate at 80∘C for appropriate time andprogress of the reaction was monitored by TLC (Scheme 2Table 2) After completion the suspension was cooled ethyl
Journal of Chemistry 5
acetate evaporated and ethanol was added to dissolve anyimpurities since the 14-dihydropyridines donot dissolve inethanolThe obtained solid was pure and characterized by 1HNMR and IR
4 Conclusions
We demonstrated the synthesis of a good range of 14-dihydropyridines which have a carbamate moiety on the 4-position from the primary reaction of different aldehydeswith phenyl isocyanate and the subsequent reaction of theobtained carbamateswithmethyl acetoacetate in the presenceof ammonium fluoride As stated before when phenyl isoth-iocyanate was used instead of phenyl isocyanate in the samecondition the reactions did not take place
Disclosure
Theauthors of the paper do not have a direct financial relationwith the commercial identities mentioned in this paper
Acknowledgment
The authors gratefully acknowledge the financial supportfrom the Bu-Ali Sina University Hamedan Iran
References
[1] A R Trivedi D K Dodiya B H Dholariya V B Kataria VR Bhuva and V H Shah ldquoSynthesis and biological evaluationof some novel N-aryl-14- dihydropyridines as potential anti-tubercular agentsrdquo Bioorganic and Medicinal Chemistry Lettersvol 21 no 18 pp 5181ndash5183 2011
[2] V P Pandey S S BishtMMishra et al ldquoSynthesis andmolecu-lar docking studies of 1-phenyl-4-glycosyl-dihydropyridines aspotent antileishmanial agentsrdquo European Journal of MedicinalChemistry vol 45 no 6 pp 2381ndash2388 2010
[3] K Sirisha D Bikshapathi G Achaiah and V M ReddyldquoSynthesis antibacterial and antimycobacterial activities ofsomenew4-arylheteroaryl-26-dimethyl-35-bis-N-(aryl)-car-bamoyl-14-dihydropyridinesrdquo European Journal of MedicinalChemistry vol 46 no 5 pp 1564ndash1571 2011
[4] K Sirisha M C Shekhar K Umasankar et al ldquoMoleculardocking studies and in vitro screening of new dihydropyridinederivatives as human MRP1 inhibitorsrdquo Bioorganic and Medici-nal Chemistry vol 19 no 10 pp 3249ndash3254 2011
[5] M Kawase A Shah H Gaveriya et al ldquo35-Dibenzoyl-14-dihydropyridines synthesis and MDR reversal in tumor cellsrdquoBioorganic andMedicinal Chemistry vol 10 no 4 pp 1051ndash10552002
[6] M Suarez Y Verdecia B Illescas et al ldquoSynthesis and studyof novel fulleropyrrolidines bearing biologically active 14-dihydropyridinesrdquo Tetrahedron vol 59 no 46 pp 9179ndash91862003
[7] R Shan C Velazquez and E E Knaus ldquoSyntheses cal-cium channel agonist-antagonist modulation activities andnitric oxide release studies of nitrooxyalkyl 14-dihydro-26-dimethyl-3-nitro-4-(213-benzoxadiazol-4-yl) pyridine-5-carboxylate racemates enantiomers and diastereomersrdquo Jour-nal of Medicinal Chemistry vol 47 no 1 pp 254ndash261 2004
[8] N I Ryabokon R I Goncharova G Duburs and J Rzeszo-wska-Wolny ldquoA 14-dihydropyridine derivative reduces DNAdamage and stimulates DNA repair in human cells in vitrordquoMutation Research vol 587 no 1-2 pp 52ndash58 2005
[9] T Yamamoto S Niwa S Ohno et al ldquoStructure-activityrelationship study of 14-dihydropyridine derivatives blockingN-type calcium channelsrdquo Bioorganic and Medicinal ChemistryLetters vol 16 no 4 pp 798ndash802 2006
[10] R A Janis and D J Triggle ldquoNew developments in calcium ionchannel antagonistsrdquo Journal of Medicinal Chemistry vol 26pp 775ndash785 1983
[11] R H Bocker and F P Guengerich ldquoOxidation of 4-aryl-and 4-alkyl-substituted 26-dimethyl-35-bis(alkoxycarbonyl)-14-dihydropyridines by human livermicrosomes and immuno-chemical evidence for the involvement of a form of cytochromeP-450rdquo Journal of Medicinal Chemistry vol 29 no 9 pp 1596ndash1603 1986
[12] F R Buhler andW Kiowski ldquoCalcium antagonists in hyperten-sionrdquo Journal of Hypertension vol 5 no 3 pp s3ndashs10 1987
[13] V Klusa ldquoCerebrocrast Neuroprotectant cognition enhancerrdquoDrugs of the Future vol 20 no 2 pp 135ndash138 1995
[14] R G Bretzel C C Bollen E Maeser and K F FederlinldquoNephroprotective effects of nitrendipine in hypertensive typeI and type II diabetic patientsrdquo American Journal of KidneyDiseases vol 21 no 6 pp 53ndash64 1993
[15] M A Zolfigol and M Safaiee ldquoSynthesis of 14-dihydropyridi-nes under solvent-free conditionsrdquo Synlett no 5 pp 827ndash8282004
[16] S Das Sharma P Hazarika and D Konwar ldquoA simple greenand one-pot four-component synthesis of 14-dihydropyridinesand their aromatizationrdquo Catalysis Communications vol 9 no5 pp 709ndash714 2008
[17] S-X Wang Z-Y Li J-C Zhang and J-T Li ldquoThe solvent-freesynthesis of 14-dihydropyridines under ultrasound irradiationwithout catalystrdquo Ultrasonics Sonochemistry vol 15 no 5 pp677ndash680 2008
[18] N Tewari N Dwivedi and R P Tripathi ldquoTetrabutylam-monium hydrogen sulfate catalyzed eco-friendly and efficientsynthesis of glycosyl 14-dihydropyridinesrdquo Tetrahedron Lettersvol 45 no 49 pp 9011ndash9014 2004
[19] G V M Sharma K L Reddy P S Lakshmi and P R KrishnaldquoldquoIn siturdquo generated ldquoHClrdquomdashan efficient catalyst for solvent-free Hantzsch reaction at room temperature synthesis of newdihydropyridine glycoconjugatesrdquo Synthesis no 1 Article IDP05205SS pp 55ndash58 2006
[20] S Ko M N V Sastry C Lin and C-F Yao ldquoMolecular iodine-catalyzed one-pot synthesis of 4-substituted-14- dihydropyri-dine derivatives viaHantzsch reactionrdquoTetrahedron Letters vol46 no 34 pp 5771ndash5774 2005
[21] M Adharvana Chari and K Syamasundar ldquoSilica gelNaHSo4
[22] G Sabitha G S K K Reddy C S Reddy and J SYadav ldquoA novel TMSI-mediated synthesis of Hantzsch 14-dihydropyridines at ambient temperaturerdquo Tetrahedron Lettersvol 44 no 21 pp 4129ndash4131 2003
[23] S Kikuchi M Iwai H Murayama and S-I FukuzawaldquoCatalytic synthesis of 14-dihydropyridine derivatives usingscandium(III) triflaterdquo Tetrahedron Letters vol 49 no 1 pp114ndash116 2008
6 Journal of Chemistry
[24] V Sridharan P T Perumal C Avendano and J C MenendezldquoA new three-component domino synthesis of 14-dihydro-pyridinesrdquo Tetrahedron vol 63 no 21 pp 4407ndash4413 2007
[25] H Adibi H A Samimi and M Beygzadeh ldquoIron(III) trifluo-roacetate and trifluoromethanesulfonate recyclable Lewis acidcatalysts for one-pot synthesis of 34-dihydropyrimidinones ortheir sulfur analogues and 14-dihydropyridines via solvent-free Biginelli and Hantzsch condensation protocolsrdquo CatalysisCommunications vol 8 no 12 pp 2119ndash2124 2007
[26] A Kumar and R A Maurya ldquoOrganocatalysed three-com-ponent domino synthesis of 14-dihydropyridines under solventfree conditionsrdquo Tetrahedron vol 64 no 16 pp 3477ndash34822008
[27] R Gupta R Gupta S Paul andA Loupy ldquoCovalently anchoredsulfonic acid on silica gel as an efficient and reusable hetero-geneous catalyst for the one-pot synthesis of Hantzsch 14-dihydropyridines under solvent-free conditionsrdquo Synthesis no18 pp 2835ndash2838 2007
[28] A Kumar and R A Maurya ldquoEfficient synthesis of Hantzschesters and polyhydroquinoline derivatives in aqueous micellesrdquoSynlett no 6 pp 883ndash885 2008
[29] AM Zonouz and S B Hosseini ldquoMontmorillonite K10 clay anefficient catalyst for Hantzsch synthesis of 14-dihydropyridinederivativesrdquo Synthetic Communications vol 38 no 2 pp 290ndash296 2008
[30] A Debache R Boulcina A Belfaitah S Rhouati and BCarboni ldquoOne-pot synthesis of 14-dihydropyridines via aphenylboronic acid catalyzed Hantzsch three-component reac-tionrdquo Synlett no 4 pp 509ndash512 2008
[31] M M Heravi F K Behbahani H A Oskooie and R H ShoarldquoCatalytic aromatization of Hantzsch 14-dihydropyridines byferric perchlorate in acetic acidrdquoTetrahedron Letters vol 46 no16 pp 2775ndash2777 2005
[32] H R Memarian and A Mirjafari ldquoSolid state photochemistryof 14-dihydropyridinesrdquo Bioorganic and Medicinal ChemistryLetters vol 15 no 14 pp 3423ndash3425 2005
[33] A Zarghi H Sadeghi A Fassihi M Faizi and A Shafiee ldquoSyn-thesis and calcium antagonist activity of 14-dihydropyridinescontaining phenylaminoimidazolyl substituentsrdquo Farmaco vol58 no 11 pp 1077ndash1081 2003
[34] A Dondoni A Massi and E Minghini ldquoTwo- andthree-component Hantzsch reaction using C-glycosylatedreagents Approach to the asymmetric synthesis of 14-diyhydropyridinesrdquo Synlett no 1 pp 89ndash92 2002
[35] MNasrollahzadeh Y Bayat DHabibi and SMoshaee ldquoFeCl3-
SiO2as a reusable heterogeneous catalyst for the synthesis of
5-substituted 1H-tetrazoles via [2+3] cycloaddition of nitrilesand sodium aziderdquoTetrahedron Letters vol 50 no 31 pp 4435ndash4438 2009
[36] D Habibi M Nasrollahzadeh A R Faraji and Y Bayat ldquoEffi-cient synthesis of arylaminotetrazoles in waterrdquo Tetrahedronvol 66 no 21 pp 3866ndash3870 2010
[37] M Nasrollahzadeh D Habibi Z Shahkarami and Y BayatldquoA general synthetic method for the formation of arylaminote-trazoles using natural natrolite zeolite as a new and reusableheterogeneous catalystrdquo Tetrahedron vol 65 no 51 pp 10715ndash10719 2009
catalyst for the preparation of arylaminotetrazolesrdquo SyntheticCommunications vol 40 no 21 pp 3159ndash3167 2010
[39] D Habibi and M Nasrollahzadeh ldquoSynthesis of arylaminote-trazoles by ZnCl
2AlCl
3silica as an efficient heterogeneous
catalystrdquo Monatshefte fur Chemie vol 143 no 6 pp 925ndash9302012
[40] DHabibiMNasrollahzadeh and T A Kamali ldquoGreen synthe-sis of the 1-substituted 1H-1234-tetrazoles by application of theNatrolite zeolite as a new and reusable heterogeneous catalystrdquoGreen Chemistry vol 13 no 12 pp 3499ndash3504 2011
[41] D Habibi and M Nasrollahzadeh ldquoZnO as an effectiveand reusable heterogeneous catalyst for the synthesis ofary-laminotetrazolesrdquo Synthetic Communications vol 42 pp 2023ndash2032 2012
Scheme 2 Preparation of different 14-dihydropyridines from carbamates and methyl acetoacetate
NH
O
O
NH
NH
O
NH
(NH4)2CO3 2NH3 + H2CO3
H2CO3
HeatCO2 + H2O
H2OH3COOC H3COOCCOOCH3 COOCH3
H3C H3CCH3 CH3
OH + HO
3a2a
Scheme 3 Hydrolysis of 2a
NH
H
OO
NH
H3COOC COOCH3
CH3H3C
1151110105100
959085807570656055504540353025201510
3540000 3000 2000 1500 1000 5500
(cmminus1)
T(
)
Figure 1 IR spectrum of dimethyl 26-dimethyl-4-(4-(phenylcarbamoyloxy)phenyl)-14-dihydropyridine-35-dicarboxylate (2a)
4 Journal of Chemistry
Table 2 Synthesis of 14-dihydropyridine derivatives (2andashf)
Entry Carbamates Product Yielda Time (h) Mp ∘C
1HN C
O
O CHO1a
NH
O
ONH
H3COOC COOCH3
CH3H3C
2a88 17 240ndash243
2
CHOHN C
O
O1b
NH
OO
NH
H3COOC COOCH3
CH3H3C
2b91 24 233ndash238
3 CHOHN C
O
O
OMe1c
NH
O
O
NH
MeOH3COOC COOCH3
CH3H3C
2c75 24 228ndash234
4 CHO
OEt
HN C
O
O
1d
NH
O
ONH
EtOH3COOC COOCH3
CH3H3C
2d53 24 225ndash230
5 CHOHN C
O
OCl
Cl 1e
Cl
Cl
NH
OO
NH
H3COOC COOCH3
CH3H3C
2e 70 20 242ndash248
6
CHO
Cl
Cl
HN C
O
O
1f
Cl
Cl
NH
OO
NH
COOCH3
CH3
H3COOC
H3C
2f 69 20 232ndash244
aIsolated yield
solvent-free at 70∘C in an appropriate time and progress ofthe reaction wasmonitored by TLC (Scheme 1 Table 1) Aftercompletion the suspension was cooled ethyl acetate evap-orated the solid was crystallized in ethanol to get the purecarbamates and the obtained crystals were characterized by1H NMR and IR
32 Typical Procedure for the Synthesis of 14-Dihydropyridines(2andashf) A mixture of carbamate (10mM) methyl acetoac-etate (20mM) and ammonium fluoride (20mM) wasstirred in ethyl acetate at 80∘C for appropriate time andprogress of the reaction was monitored by TLC (Scheme 2Table 2) After completion the suspension was cooled ethyl
Journal of Chemistry 5
acetate evaporated and ethanol was added to dissolve anyimpurities since the 14-dihydropyridines donot dissolve inethanolThe obtained solid was pure and characterized by 1HNMR and IR
4 Conclusions
We demonstrated the synthesis of a good range of 14-dihydropyridines which have a carbamate moiety on the 4-position from the primary reaction of different aldehydeswith phenyl isocyanate and the subsequent reaction of theobtained carbamateswithmethyl acetoacetate in the presenceof ammonium fluoride As stated before when phenyl isoth-iocyanate was used instead of phenyl isocyanate in the samecondition the reactions did not take place
Disclosure
Theauthors of the paper do not have a direct financial relationwith the commercial identities mentioned in this paper
Acknowledgment
The authors gratefully acknowledge the financial supportfrom the Bu-Ali Sina University Hamedan Iran
References
[1] A R Trivedi D K Dodiya B H Dholariya V B Kataria VR Bhuva and V H Shah ldquoSynthesis and biological evaluationof some novel N-aryl-14- dihydropyridines as potential anti-tubercular agentsrdquo Bioorganic and Medicinal Chemistry Lettersvol 21 no 18 pp 5181ndash5183 2011
[2] V P Pandey S S BishtMMishra et al ldquoSynthesis andmolecu-lar docking studies of 1-phenyl-4-glycosyl-dihydropyridines aspotent antileishmanial agentsrdquo European Journal of MedicinalChemistry vol 45 no 6 pp 2381ndash2388 2010
[3] K Sirisha D Bikshapathi G Achaiah and V M ReddyldquoSynthesis antibacterial and antimycobacterial activities ofsomenew4-arylheteroaryl-26-dimethyl-35-bis-N-(aryl)-car-bamoyl-14-dihydropyridinesrdquo European Journal of MedicinalChemistry vol 46 no 5 pp 1564ndash1571 2011
[4] K Sirisha M C Shekhar K Umasankar et al ldquoMoleculardocking studies and in vitro screening of new dihydropyridinederivatives as human MRP1 inhibitorsrdquo Bioorganic and Medici-nal Chemistry vol 19 no 10 pp 3249ndash3254 2011
[5] M Kawase A Shah H Gaveriya et al ldquo35-Dibenzoyl-14-dihydropyridines synthesis and MDR reversal in tumor cellsrdquoBioorganic andMedicinal Chemistry vol 10 no 4 pp 1051ndash10552002
[6] M Suarez Y Verdecia B Illescas et al ldquoSynthesis and studyof novel fulleropyrrolidines bearing biologically active 14-dihydropyridinesrdquo Tetrahedron vol 59 no 46 pp 9179ndash91862003
[7] R Shan C Velazquez and E E Knaus ldquoSyntheses cal-cium channel agonist-antagonist modulation activities andnitric oxide release studies of nitrooxyalkyl 14-dihydro-26-dimethyl-3-nitro-4-(213-benzoxadiazol-4-yl) pyridine-5-carboxylate racemates enantiomers and diastereomersrdquo Jour-nal of Medicinal Chemistry vol 47 no 1 pp 254ndash261 2004
[8] N I Ryabokon R I Goncharova G Duburs and J Rzeszo-wska-Wolny ldquoA 14-dihydropyridine derivative reduces DNAdamage and stimulates DNA repair in human cells in vitrordquoMutation Research vol 587 no 1-2 pp 52ndash58 2005
[9] T Yamamoto S Niwa S Ohno et al ldquoStructure-activityrelationship study of 14-dihydropyridine derivatives blockingN-type calcium channelsrdquo Bioorganic and Medicinal ChemistryLetters vol 16 no 4 pp 798ndash802 2006
[10] R A Janis and D J Triggle ldquoNew developments in calcium ionchannel antagonistsrdquo Journal of Medicinal Chemistry vol 26pp 775ndash785 1983
[11] R H Bocker and F P Guengerich ldquoOxidation of 4-aryl-and 4-alkyl-substituted 26-dimethyl-35-bis(alkoxycarbonyl)-14-dihydropyridines by human livermicrosomes and immuno-chemical evidence for the involvement of a form of cytochromeP-450rdquo Journal of Medicinal Chemistry vol 29 no 9 pp 1596ndash1603 1986
[12] F R Buhler andW Kiowski ldquoCalcium antagonists in hyperten-sionrdquo Journal of Hypertension vol 5 no 3 pp s3ndashs10 1987
[13] V Klusa ldquoCerebrocrast Neuroprotectant cognition enhancerrdquoDrugs of the Future vol 20 no 2 pp 135ndash138 1995
[14] R G Bretzel C C Bollen E Maeser and K F FederlinldquoNephroprotective effects of nitrendipine in hypertensive typeI and type II diabetic patientsrdquo American Journal of KidneyDiseases vol 21 no 6 pp 53ndash64 1993
[15] M A Zolfigol and M Safaiee ldquoSynthesis of 14-dihydropyridi-nes under solvent-free conditionsrdquo Synlett no 5 pp 827ndash8282004
[16] S Das Sharma P Hazarika and D Konwar ldquoA simple greenand one-pot four-component synthesis of 14-dihydropyridinesand their aromatizationrdquo Catalysis Communications vol 9 no5 pp 709ndash714 2008
[17] S-X Wang Z-Y Li J-C Zhang and J-T Li ldquoThe solvent-freesynthesis of 14-dihydropyridines under ultrasound irradiationwithout catalystrdquo Ultrasonics Sonochemistry vol 15 no 5 pp677ndash680 2008
[18] N Tewari N Dwivedi and R P Tripathi ldquoTetrabutylam-monium hydrogen sulfate catalyzed eco-friendly and efficientsynthesis of glycosyl 14-dihydropyridinesrdquo Tetrahedron Lettersvol 45 no 49 pp 9011ndash9014 2004
[19] G V M Sharma K L Reddy P S Lakshmi and P R KrishnaldquoldquoIn siturdquo generated ldquoHClrdquomdashan efficient catalyst for solvent-free Hantzsch reaction at room temperature synthesis of newdihydropyridine glycoconjugatesrdquo Synthesis no 1 Article IDP05205SS pp 55ndash58 2006
[20] S Ko M N V Sastry C Lin and C-F Yao ldquoMolecular iodine-catalyzed one-pot synthesis of 4-substituted-14- dihydropyri-dine derivatives viaHantzsch reactionrdquoTetrahedron Letters vol46 no 34 pp 5771ndash5774 2005
[21] M Adharvana Chari and K Syamasundar ldquoSilica gelNaHSo4
[22] G Sabitha G S K K Reddy C S Reddy and J SYadav ldquoA novel TMSI-mediated synthesis of Hantzsch 14-dihydropyridines at ambient temperaturerdquo Tetrahedron Lettersvol 44 no 21 pp 4129ndash4131 2003
[23] S Kikuchi M Iwai H Murayama and S-I FukuzawaldquoCatalytic synthesis of 14-dihydropyridine derivatives usingscandium(III) triflaterdquo Tetrahedron Letters vol 49 no 1 pp114ndash116 2008
6 Journal of Chemistry
[24] V Sridharan P T Perumal C Avendano and J C MenendezldquoA new three-component domino synthesis of 14-dihydro-pyridinesrdquo Tetrahedron vol 63 no 21 pp 4407ndash4413 2007
[25] H Adibi H A Samimi and M Beygzadeh ldquoIron(III) trifluo-roacetate and trifluoromethanesulfonate recyclable Lewis acidcatalysts for one-pot synthesis of 34-dihydropyrimidinones ortheir sulfur analogues and 14-dihydropyridines via solvent-free Biginelli and Hantzsch condensation protocolsrdquo CatalysisCommunications vol 8 no 12 pp 2119ndash2124 2007
[26] A Kumar and R A Maurya ldquoOrganocatalysed three-com-ponent domino synthesis of 14-dihydropyridines under solventfree conditionsrdquo Tetrahedron vol 64 no 16 pp 3477ndash34822008
[27] R Gupta R Gupta S Paul andA Loupy ldquoCovalently anchoredsulfonic acid on silica gel as an efficient and reusable hetero-geneous catalyst for the one-pot synthesis of Hantzsch 14-dihydropyridines under solvent-free conditionsrdquo Synthesis no18 pp 2835ndash2838 2007
[28] A Kumar and R A Maurya ldquoEfficient synthesis of Hantzschesters and polyhydroquinoline derivatives in aqueous micellesrdquoSynlett no 6 pp 883ndash885 2008
[29] AM Zonouz and S B Hosseini ldquoMontmorillonite K10 clay anefficient catalyst for Hantzsch synthesis of 14-dihydropyridinederivativesrdquo Synthetic Communications vol 38 no 2 pp 290ndash296 2008
[30] A Debache R Boulcina A Belfaitah S Rhouati and BCarboni ldquoOne-pot synthesis of 14-dihydropyridines via aphenylboronic acid catalyzed Hantzsch three-component reac-tionrdquo Synlett no 4 pp 509ndash512 2008
[31] M M Heravi F K Behbahani H A Oskooie and R H ShoarldquoCatalytic aromatization of Hantzsch 14-dihydropyridines byferric perchlorate in acetic acidrdquoTetrahedron Letters vol 46 no16 pp 2775ndash2777 2005
[32] H R Memarian and A Mirjafari ldquoSolid state photochemistryof 14-dihydropyridinesrdquo Bioorganic and Medicinal ChemistryLetters vol 15 no 14 pp 3423ndash3425 2005
[33] A Zarghi H Sadeghi A Fassihi M Faizi and A Shafiee ldquoSyn-thesis and calcium antagonist activity of 14-dihydropyridinescontaining phenylaminoimidazolyl substituentsrdquo Farmaco vol58 no 11 pp 1077ndash1081 2003
[34] A Dondoni A Massi and E Minghini ldquoTwo- andthree-component Hantzsch reaction using C-glycosylatedreagents Approach to the asymmetric synthesis of 14-diyhydropyridinesrdquo Synlett no 1 pp 89ndash92 2002
[35] MNasrollahzadeh Y Bayat DHabibi and SMoshaee ldquoFeCl3-
SiO2as a reusable heterogeneous catalyst for the synthesis of
5-substituted 1H-tetrazoles via [2+3] cycloaddition of nitrilesand sodium aziderdquoTetrahedron Letters vol 50 no 31 pp 4435ndash4438 2009
[36] D Habibi M Nasrollahzadeh A R Faraji and Y Bayat ldquoEffi-cient synthesis of arylaminotetrazoles in waterrdquo Tetrahedronvol 66 no 21 pp 3866ndash3870 2010
[37] M Nasrollahzadeh D Habibi Z Shahkarami and Y BayatldquoA general synthetic method for the formation of arylaminote-trazoles using natural natrolite zeolite as a new and reusableheterogeneous catalystrdquo Tetrahedron vol 65 no 51 pp 10715ndash10719 2009
catalyst for the preparation of arylaminotetrazolesrdquo SyntheticCommunications vol 40 no 21 pp 3159ndash3167 2010
[39] D Habibi and M Nasrollahzadeh ldquoSynthesis of arylaminote-trazoles by ZnCl
2AlCl
3silica as an efficient heterogeneous
catalystrdquo Monatshefte fur Chemie vol 143 no 6 pp 925ndash9302012
[40] DHabibiMNasrollahzadeh and T A Kamali ldquoGreen synthe-sis of the 1-substituted 1H-1234-tetrazoles by application of theNatrolite zeolite as a new and reusable heterogeneous catalystrdquoGreen Chemistry vol 13 no 12 pp 3499ndash3504 2011
[41] D Habibi and M Nasrollahzadeh ldquoZnO as an effectiveand reusable heterogeneous catalyst for the synthesis ofary-laminotetrazolesrdquo Synthetic Communications vol 42 pp 2023ndash2032 2012
Table 2 Synthesis of 14-dihydropyridine derivatives (2andashf)
Entry Carbamates Product Yielda Time (h) Mp ∘C
1HN C
O
O CHO1a
NH
O
ONH
H3COOC COOCH3
CH3H3C
2a88 17 240ndash243
2
CHOHN C
O
O1b
NH
OO
NH
H3COOC COOCH3
CH3H3C
2b91 24 233ndash238
3 CHOHN C
O
O
OMe1c
NH
O
O
NH
MeOH3COOC COOCH3
CH3H3C
2c75 24 228ndash234
4 CHO
OEt
HN C
O
O
1d
NH
O
ONH
EtOH3COOC COOCH3
CH3H3C
2d53 24 225ndash230
5 CHOHN C
O
OCl
Cl 1e
Cl
Cl
NH
OO
NH
H3COOC COOCH3
CH3H3C
2e 70 20 242ndash248
6
CHO
Cl
Cl
HN C
O
O
1f
Cl
Cl
NH
OO
NH
COOCH3
CH3
H3COOC
H3C
2f 69 20 232ndash244
aIsolated yield
solvent-free at 70∘C in an appropriate time and progress ofthe reaction wasmonitored by TLC (Scheme 1 Table 1) Aftercompletion the suspension was cooled ethyl acetate evap-orated the solid was crystallized in ethanol to get the purecarbamates and the obtained crystals were characterized by1H NMR and IR
32 Typical Procedure for the Synthesis of 14-Dihydropyridines(2andashf) A mixture of carbamate (10mM) methyl acetoac-etate (20mM) and ammonium fluoride (20mM) wasstirred in ethyl acetate at 80∘C for appropriate time andprogress of the reaction was monitored by TLC (Scheme 2Table 2) After completion the suspension was cooled ethyl
Journal of Chemistry 5
acetate evaporated and ethanol was added to dissolve anyimpurities since the 14-dihydropyridines donot dissolve inethanolThe obtained solid was pure and characterized by 1HNMR and IR
4 Conclusions
We demonstrated the synthesis of a good range of 14-dihydropyridines which have a carbamate moiety on the 4-position from the primary reaction of different aldehydeswith phenyl isocyanate and the subsequent reaction of theobtained carbamateswithmethyl acetoacetate in the presenceof ammonium fluoride As stated before when phenyl isoth-iocyanate was used instead of phenyl isocyanate in the samecondition the reactions did not take place
Disclosure
Theauthors of the paper do not have a direct financial relationwith the commercial identities mentioned in this paper
Acknowledgment
The authors gratefully acknowledge the financial supportfrom the Bu-Ali Sina University Hamedan Iran
References
[1] A R Trivedi D K Dodiya B H Dholariya V B Kataria VR Bhuva and V H Shah ldquoSynthesis and biological evaluationof some novel N-aryl-14- dihydropyridines as potential anti-tubercular agentsrdquo Bioorganic and Medicinal Chemistry Lettersvol 21 no 18 pp 5181ndash5183 2011
[2] V P Pandey S S BishtMMishra et al ldquoSynthesis andmolecu-lar docking studies of 1-phenyl-4-glycosyl-dihydropyridines aspotent antileishmanial agentsrdquo European Journal of MedicinalChemistry vol 45 no 6 pp 2381ndash2388 2010
[3] K Sirisha D Bikshapathi G Achaiah and V M ReddyldquoSynthesis antibacterial and antimycobacterial activities ofsomenew4-arylheteroaryl-26-dimethyl-35-bis-N-(aryl)-car-bamoyl-14-dihydropyridinesrdquo European Journal of MedicinalChemistry vol 46 no 5 pp 1564ndash1571 2011
[4] K Sirisha M C Shekhar K Umasankar et al ldquoMoleculardocking studies and in vitro screening of new dihydropyridinederivatives as human MRP1 inhibitorsrdquo Bioorganic and Medici-nal Chemistry vol 19 no 10 pp 3249ndash3254 2011
[5] M Kawase A Shah H Gaveriya et al ldquo35-Dibenzoyl-14-dihydropyridines synthesis and MDR reversal in tumor cellsrdquoBioorganic andMedicinal Chemistry vol 10 no 4 pp 1051ndash10552002
[6] M Suarez Y Verdecia B Illescas et al ldquoSynthesis and studyof novel fulleropyrrolidines bearing biologically active 14-dihydropyridinesrdquo Tetrahedron vol 59 no 46 pp 9179ndash91862003
[7] R Shan C Velazquez and E E Knaus ldquoSyntheses cal-cium channel agonist-antagonist modulation activities andnitric oxide release studies of nitrooxyalkyl 14-dihydro-26-dimethyl-3-nitro-4-(213-benzoxadiazol-4-yl) pyridine-5-carboxylate racemates enantiomers and diastereomersrdquo Jour-nal of Medicinal Chemistry vol 47 no 1 pp 254ndash261 2004
[8] N I Ryabokon R I Goncharova G Duburs and J Rzeszo-wska-Wolny ldquoA 14-dihydropyridine derivative reduces DNAdamage and stimulates DNA repair in human cells in vitrordquoMutation Research vol 587 no 1-2 pp 52ndash58 2005
[9] T Yamamoto S Niwa S Ohno et al ldquoStructure-activityrelationship study of 14-dihydropyridine derivatives blockingN-type calcium channelsrdquo Bioorganic and Medicinal ChemistryLetters vol 16 no 4 pp 798ndash802 2006
[10] R A Janis and D J Triggle ldquoNew developments in calcium ionchannel antagonistsrdquo Journal of Medicinal Chemistry vol 26pp 775ndash785 1983
[11] R H Bocker and F P Guengerich ldquoOxidation of 4-aryl-and 4-alkyl-substituted 26-dimethyl-35-bis(alkoxycarbonyl)-14-dihydropyridines by human livermicrosomes and immuno-chemical evidence for the involvement of a form of cytochromeP-450rdquo Journal of Medicinal Chemistry vol 29 no 9 pp 1596ndash1603 1986
[12] F R Buhler andW Kiowski ldquoCalcium antagonists in hyperten-sionrdquo Journal of Hypertension vol 5 no 3 pp s3ndashs10 1987
[13] V Klusa ldquoCerebrocrast Neuroprotectant cognition enhancerrdquoDrugs of the Future vol 20 no 2 pp 135ndash138 1995
[14] R G Bretzel C C Bollen E Maeser and K F FederlinldquoNephroprotective effects of nitrendipine in hypertensive typeI and type II diabetic patientsrdquo American Journal of KidneyDiseases vol 21 no 6 pp 53ndash64 1993
[15] M A Zolfigol and M Safaiee ldquoSynthesis of 14-dihydropyridi-nes under solvent-free conditionsrdquo Synlett no 5 pp 827ndash8282004
[16] S Das Sharma P Hazarika and D Konwar ldquoA simple greenand one-pot four-component synthesis of 14-dihydropyridinesand their aromatizationrdquo Catalysis Communications vol 9 no5 pp 709ndash714 2008
[17] S-X Wang Z-Y Li J-C Zhang and J-T Li ldquoThe solvent-freesynthesis of 14-dihydropyridines under ultrasound irradiationwithout catalystrdquo Ultrasonics Sonochemistry vol 15 no 5 pp677ndash680 2008
[18] N Tewari N Dwivedi and R P Tripathi ldquoTetrabutylam-monium hydrogen sulfate catalyzed eco-friendly and efficientsynthesis of glycosyl 14-dihydropyridinesrdquo Tetrahedron Lettersvol 45 no 49 pp 9011ndash9014 2004
[19] G V M Sharma K L Reddy P S Lakshmi and P R KrishnaldquoldquoIn siturdquo generated ldquoHClrdquomdashan efficient catalyst for solvent-free Hantzsch reaction at room temperature synthesis of newdihydropyridine glycoconjugatesrdquo Synthesis no 1 Article IDP05205SS pp 55ndash58 2006
[20] S Ko M N V Sastry C Lin and C-F Yao ldquoMolecular iodine-catalyzed one-pot synthesis of 4-substituted-14- dihydropyri-dine derivatives viaHantzsch reactionrdquoTetrahedron Letters vol46 no 34 pp 5771ndash5774 2005
[21] M Adharvana Chari and K Syamasundar ldquoSilica gelNaHSo4
[22] G Sabitha G S K K Reddy C S Reddy and J SYadav ldquoA novel TMSI-mediated synthesis of Hantzsch 14-dihydropyridines at ambient temperaturerdquo Tetrahedron Lettersvol 44 no 21 pp 4129ndash4131 2003
[23] S Kikuchi M Iwai H Murayama and S-I FukuzawaldquoCatalytic synthesis of 14-dihydropyridine derivatives usingscandium(III) triflaterdquo Tetrahedron Letters vol 49 no 1 pp114ndash116 2008
6 Journal of Chemistry
[24] V Sridharan P T Perumal C Avendano and J C MenendezldquoA new three-component domino synthesis of 14-dihydro-pyridinesrdquo Tetrahedron vol 63 no 21 pp 4407ndash4413 2007
[25] H Adibi H A Samimi and M Beygzadeh ldquoIron(III) trifluo-roacetate and trifluoromethanesulfonate recyclable Lewis acidcatalysts for one-pot synthesis of 34-dihydropyrimidinones ortheir sulfur analogues and 14-dihydropyridines via solvent-free Biginelli and Hantzsch condensation protocolsrdquo CatalysisCommunications vol 8 no 12 pp 2119ndash2124 2007
[26] A Kumar and R A Maurya ldquoOrganocatalysed three-com-ponent domino synthesis of 14-dihydropyridines under solventfree conditionsrdquo Tetrahedron vol 64 no 16 pp 3477ndash34822008
[27] R Gupta R Gupta S Paul andA Loupy ldquoCovalently anchoredsulfonic acid on silica gel as an efficient and reusable hetero-geneous catalyst for the one-pot synthesis of Hantzsch 14-dihydropyridines under solvent-free conditionsrdquo Synthesis no18 pp 2835ndash2838 2007
[28] A Kumar and R A Maurya ldquoEfficient synthesis of Hantzschesters and polyhydroquinoline derivatives in aqueous micellesrdquoSynlett no 6 pp 883ndash885 2008
[29] AM Zonouz and S B Hosseini ldquoMontmorillonite K10 clay anefficient catalyst for Hantzsch synthesis of 14-dihydropyridinederivativesrdquo Synthetic Communications vol 38 no 2 pp 290ndash296 2008
[30] A Debache R Boulcina A Belfaitah S Rhouati and BCarboni ldquoOne-pot synthesis of 14-dihydropyridines via aphenylboronic acid catalyzed Hantzsch three-component reac-tionrdquo Synlett no 4 pp 509ndash512 2008
[31] M M Heravi F K Behbahani H A Oskooie and R H ShoarldquoCatalytic aromatization of Hantzsch 14-dihydropyridines byferric perchlorate in acetic acidrdquoTetrahedron Letters vol 46 no16 pp 2775ndash2777 2005
[32] H R Memarian and A Mirjafari ldquoSolid state photochemistryof 14-dihydropyridinesrdquo Bioorganic and Medicinal ChemistryLetters vol 15 no 14 pp 3423ndash3425 2005
[33] A Zarghi H Sadeghi A Fassihi M Faizi and A Shafiee ldquoSyn-thesis and calcium antagonist activity of 14-dihydropyridinescontaining phenylaminoimidazolyl substituentsrdquo Farmaco vol58 no 11 pp 1077ndash1081 2003
[34] A Dondoni A Massi and E Minghini ldquoTwo- andthree-component Hantzsch reaction using C-glycosylatedreagents Approach to the asymmetric synthesis of 14-diyhydropyridinesrdquo Synlett no 1 pp 89ndash92 2002
[35] MNasrollahzadeh Y Bayat DHabibi and SMoshaee ldquoFeCl3-
SiO2as a reusable heterogeneous catalyst for the synthesis of
5-substituted 1H-tetrazoles via [2+3] cycloaddition of nitrilesand sodium aziderdquoTetrahedron Letters vol 50 no 31 pp 4435ndash4438 2009
[36] D Habibi M Nasrollahzadeh A R Faraji and Y Bayat ldquoEffi-cient synthesis of arylaminotetrazoles in waterrdquo Tetrahedronvol 66 no 21 pp 3866ndash3870 2010
[37] M Nasrollahzadeh D Habibi Z Shahkarami and Y BayatldquoA general synthetic method for the formation of arylaminote-trazoles using natural natrolite zeolite as a new and reusableheterogeneous catalystrdquo Tetrahedron vol 65 no 51 pp 10715ndash10719 2009
catalyst for the preparation of arylaminotetrazolesrdquo SyntheticCommunications vol 40 no 21 pp 3159ndash3167 2010
[39] D Habibi and M Nasrollahzadeh ldquoSynthesis of arylaminote-trazoles by ZnCl
2AlCl
3silica as an efficient heterogeneous
catalystrdquo Monatshefte fur Chemie vol 143 no 6 pp 925ndash9302012
[40] DHabibiMNasrollahzadeh and T A Kamali ldquoGreen synthe-sis of the 1-substituted 1H-1234-tetrazoles by application of theNatrolite zeolite as a new and reusable heterogeneous catalystrdquoGreen Chemistry vol 13 no 12 pp 3499ndash3504 2011
[41] D Habibi and M Nasrollahzadeh ldquoZnO as an effectiveand reusable heterogeneous catalyst for the synthesis ofary-laminotetrazolesrdquo Synthetic Communications vol 42 pp 2023ndash2032 2012
acetate evaporated and ethanol was added to dissolve anyimpurities since the 14-dihydropyridines donot dissolve inethanolThe obtained solid was pure and characterized by 1HNMR and IR
4 Conclusions
We demonstrated the synthesis of a good range of 14-dihydropyridines which have a carbamate moiety on the 4-position from the primary reaction of different aldehydeswith phenyl isocyanate and the subsequent reaction of theobtained carbamateswithmethyl acetoacetate in the presenceof ammonium fluoride As stated before when phenyl isoth-iocyanate was used instead of phenyl isocyanate in the samecondition the reactions did not take place
Disclosure
Theauthors of the paper do not have a direct financial relationwith the commercial identities mentioned in this paper
Acknowledgment
The authors gratefully acknowledge the financial supportfrom the Bu-Ali Sina University Hamedan Iran
References
[1] A R Trivedi D K Dodiya B H Dholariya V B Kataria VR Bhuva and V H Shah ldquoSynthesis and biological evaluationof some novel N-aryl-14- dihydropyridines as potential anti-tubercular agentsrdquo Bioorganic and Medicinal Chemistry Lettersvol 21 no 18 pp 5181ndash5183 2011
[2] V P Pandey S S BishtMMishra et al ldquoSynthesis andmolecu-lar docking studies of 1-phenyl-4-glycosyl-dihydropyridines aspotent antileishmanial agentsrdquo European Journal of MedicinalChemistry vol 45 no 6 pp 2381ndash2388 2010
[3] K Sirisha D Bikshapathi G Achaiah and V M ReddyldquoSynthesis antibacterial and antimycobacterial activities ofsomenew4-arylheteroaryl-26-dimethyl-35-bis-N-(aryl)-car-bamoyl-14-dihydropyridinesrdquo European Journal of MedicinalChemistry vol 46 no 5 pp 1564ndash1571 2011
[4] K Sirisha M C Shekhar K Umasankar et al ldquoMoleculardocking studies and in vitro screening of new dihydropyridinederivatives as human MRP1 inhibitorsrdquo Bioorganic and Medici-nal Chemistry vol 19 no 10 pp 3249ndash3254 2011
[5] M Kawase A Shah H Gaveriya et al ldquo35-Dibenzoyl-14-dihydropyridines synthesis and MDR reversal in tumor cellsrdquoBioorganic andMedicinal Chemistry vol 10 no 4 pp 1051ndash10552002
[6] M Suarez Y Verdecia B Illescas et al ldquoSynthesis and studyof novel fulleropyrrolidines bearing biologically active 14-dihydropyridinesrdquo Tetrahedron vol 59 no 46 pp 9179ndash91862003
[7] R Shan C Velazquez and E E Knaus ldquoSyntheses cal-cium channel agonist-antagonist modulation activities andnitric oxide release studies of nitrooxyalkyl 14-dihydro-26-dimethyl-3-nitro-4-(213-benzoxadiazol-4-yl) pyridine-5-carboxylate racemates enantiomers and diastereomersrdquo Jour-nal of Medicinal Chemistry vol 47 no 1 pp 254ndash261 2004
[8] N I Ryabokon R I Goncharova G Duburs and J Rzeszo-wska-Wolny ldquoA 14-dihydropyridine derivative reduces DNAdamage and stimulates DNA repair in human cells in vitrordquoMutation Research vol 587 no 1-2 pp 52ndash58 2005
[9] T Yamamoto S Niwa S Ohno et al ldquoStructure-activityrelationship study of 14-dihydropyridine derivatives blockingN-type calcium channelsrdquo Bioorganic and Medicinal ChemistryLetters vol 16 no 4 pp 798ndash802 2006
[10] R A Janis and D J Triggle ldquoNew developments in calcium ionchannel antagonistsrdquo Journal of Medicinal Chemistry vol 26pp 775ndash785 1983
[11] R H Bocker and F P Guengerich ldquoOxidation of 4-aryl-and 4-alkyl-substituted 26-dimethyl-35-bis(alkoxycarbonyl)-14-dihydropyridines by human livermicrosomes and immuno-chemical evidence for the involvement of a form of cytochromeP-450rdquo Journal of Medicinal Chemistry vol 29 no 9 pp 1596ndash1603 1986
[12] F R Buhler andW Kiowski ldquoCalcium antagonists in hyperten-sionrdquo Journal of Hypertension vol 5 no 3 pp s3ndashs10 1987
[13] V Klusa ldquoCerebrocrast Neuroprotectant cognition enhancerrdquoDrugs of the Future vol 20 no 2 pp 135ndash138 1995
[14] R G Bretzel C C Bollen E Maeser and K F FederlinldquoNephroprotective effects of nitrendipine in hypertensive typeI and type II diabetic patientsrdquo American Journal of KidneyDiseases vol 21 no 6 pp 53ndash64 1993
[15] M A Zolfigol and M Safaiee ldquoSynthesis of 14-dihydropyridi-nes under solvent-free conditionsrdquo Synlett no 5 pp 827ndash8282004
[16] S Das Sharma P Hazarika and D Konwar ldquoA simple greenand one-pot four-component synthesis of 14-dihydropyridinesand their aromatizationrdquo Catalysis Communications vol 9 no5 pp 709ndash714 2008
[17] S-X Wang Z-Y Li J-C Zhang and J-T Li ldquoThe solvent-freesynthesis of 14-dihydropyridines under ultrasound irradiationwithout catalystrdquo Ultrasonics Sonochemistry vol 15 no 5 pp677ndash680 2008
[18] N Tewari N Dwivedi and R P Tripathi ldquoTetrabutylam-monium hydrogen sulfate catalyzed eco-friendly and efficientsynthesis of glycosyl 14-dihydropyridinesrdquo Tetrahedron Lettersvol 45 no 49 pp 9011ndash9014 2004
[19] G V M Sharma K L Reddy P S Lakshmi and P R KrishnaldquoldquoIn siturdquo generated ldquoHClrdquomdashan efficient catalyst for solvent-free Hantzsch reaction at room temperature synthesis of newdihydropyridine glycoconjugatesrdquo Synthesis no 1 Article IDP05205SS pp 55ndash58 2006
[20] S Ko M N V Sastry C Lin and C-F Yao ldquoMolecular iodine-catalyzed one-pot synthesis of 4-substituted-14- dihydropyri-dine derivatives viaHantzsch reactionrdquoTetrahedron Letters vol46 no 34 pp 5771ndash5774 2005
[21] M Adharvana Chari and K Syamasundar ldquoSilica gelNaHSo4
[22] G Sabitha G S K K Reddy C S Reddy and J SYadav ldquoA novel TMSI-mediated synthesis of Hantzsch 14-dihydropyridines at ambient temperaturerdquo Tetrahedron Lettersvol 44 no 21 pp 4129ndash4131 2003
[23] S Kikuchi M Iwai H Murayama and S-I FukuzawaldquoCatalytic synthesis of 14-dihydropyridine derivatives usingscandium(III) triflaterdquo Tetrahedron Letters vol 49 no 1 pp114ndash116 2008
6 Journal of Chemistry
[24] V Sridharan P T Perumal C Avendano and J C MenendezldquoA new three-component domino synthesis of 14-dihydro-pyridinesrdquo Tetrahedron vol 63 no 21 pp 4407ndash4413 2007
[25] H Adibi H A Samimi and M Beygzadeh ldquoIron(III) trifluo-roacetate and trifluoromethanesulfonate recyclable Lewis acidcatalysts for one-pot synthesis of 34-dihydropyrimidinones ortheir sulfur analogues and 14-dihydropyridines via solvent-free Biginelli and Hantzsch condensation protocolsrdquo CatalysisCommunications vol 8 no 12 pp 2119ndash2124 2007
[26] A Kumar and R A Maurya ldquoOrganocatalysed three-com-ponent domino synthesis of 14-dihydropyridines under solventfree conditionsrdquo Tetrahedron vol 64 no 16 pp 3477ndash34822008
[27] R Gupta R Gupta S Paul andA Loupy ldquoCovalently anchoredsulfonic acid on silica gel as an efficient and reusable hetero-geneous catalyst for the one-pot synthesis of Hantzsch 14-dihydropyridines under solvent-free conditionsrdquo Synthesis no18 pp 2835ndash2838 2007
[28] A Kumar and R A Maurya ldquoEfficient synthesis of Hantzschesters and polyhydroquinoline derivatives in aqueous micellesrdquoSynlett no 6 pp 883ndash885 2008
[29] AM Zonouz and S B Hosseini ldquoMontmorillonite K10 clay anefficient catalyst for Hantzsch synthesis of 14-dihydropyridinederivativesrdquo Synthetic Communications vol 38 no 2 pp 290ndash296 2008
[30] A Debache R Boulcina A Belfaitah S Rhouati and BCarboni ldquoOne-pot synthesis of 14-dihydropyridines via aphenylboronic acid catalyzed Hantzsch three-component reac-tionrdquo Synlett no 4 pp 509ndash512 2008
[31] M M Heravi F K Behbahani H A Oskooie and R H ShoarldquoCatalytic aromatization of Hantzsch 14-dihydropyridines byferric perchlorate in acetic acidrdquoTetrahedron Letters vol 46 no16 pp 2775ndash2777 2005
[32] H R Memarian and A Mirjafari ldquoSolid state photochemistryof 14-dihydropyridinesrdquo Bioorganic and Medicinal ChemistryLetters vol 15 no 14 pp 3423ndash3425 2005
[33] A Zarghi H Sadeghi A Fassihi M Faizi and A Shafiee ldquoSyn-thesis and calcium antagonist activity of 14-dihydropyridinescontaining phenylaminoimidazolyl substituentsrdquo Farmaco vol58 no 11 pp 1077ndash1081 2003
[34] A Dondoni A Massi and E Minghini ldquoTwo- andthree-component Hantzsch reaction using C-glycosylatedreagents Approach to the asymmetric synthesis of 14-diyhydropyridinesrdquo Synlett no 1 pp 89ndash92 2002
[35] MNasrollahzadeh Y Bayat DHabibi and SMoshaee ldquoFeCl3-
SiO2as a reusable heterogeneous catalyst for the synthesis of
5-substituted 1H-tetrazoles via [2+3] cycloaddition of nitrilesand sodium aziderdquoTetrahedron Letters vol 50 no 31 pp 4435ndash4438 2009
[36] D Habibi M Nasrollahzadeh A R Faraji and Y Bayat ldquoEffi-cient synthesis of arylaminotetrazoles in waterrdquo Tetrahedronvol 66 no 21 pp 3866ndash3870 2010
[37] M Nasrollahzadeh D Habibi Z Shahkarami and Y BayatldquoA general synthetic method for the formation of arylaminote-trazoles using natural natrolite zeolite as a new and reusableheterogeneous catalystrdquo Tetrahedron vol 65 no 51 pp 10715ndash10719 2009
catalyst for the preparation of arylaminotetrazolesrdquo SyntheticCommunications vol 40 no 21 pp 3159ndash3167 2010
[39] D Habibi and M Nasrollahzadeh ldquoSynthesis of arylaminote-trazoles by ZnCl
2AlCl
3silica as an efficient heterogeneous
catalystrdquo Monatshefte fur Chemie vol 143 no 6 pp 925ndash9302012
[40] DHabibiMNasrollahzadeh and T A Kamali ldquoGreen synthe-sis of the 1-substituted 1H-1234-tetrazoles by application of theNatrolite zeolite as a new and reusable heterogeneous catalystrdquoGreen Chemistry vol 13 no 12 pp 3499ndash3504 2011
[41] D Habibi and M Nasrollahzadeh ldquoZnO as an effectiveand reusable heterogeneous catalyst for the synthesis ofary-laminotetrazolesrdquo Synthetic Communications vol 42 pp 2023ndash2032 2012
[24] V Sridharan P T Perumal C Avendano and J C MenendezldquoA new three-component domino synthesis of 14-dihydro-pyridinesrdquo Tetrahedron vol 63 no 21 pp 4407ndash4413 2007
[25] H Adibi H A Samimi and M Beygzadeh ldquoIron(III) trifluo-roacetate and trifluoromethanesulfonate recyclable Lewis acidcatalysts for one-pot synthesis of 34-dihydropyrimidinones ortheir sulfur analogues and 14-dihydropyridines via solvent-free Biginelli and Hantzsch condensation protocolsrdquo CatalysisCommunications vol 8 no 12 pp 2119ndash2124 2007
[26] A Kumar and R A Maurya ldquoOrganocatalysed three-com-ponent domino synthesis of 14-dihydropyridines under solventfree conditionsrdquo Tetrahedron vol 64 no 16 pp 3477ndash34822008
[27] R Gupta R Gupta S Paul andA Loupy ldquoCovalently anchoredsulfonic acid on silica gel as an efficient and reusable hetero-geneous catalyst for the one-pot synthesis of Hantzsch 14-dihydropyridines under solvent-free conditionsrdquo Synthesis no18 pp 2835ndash2838 2007
[28] A Kumar and R A Maurya ldquoEfficient synthesis of Hantzschesters and polyhydroquinoline derivatives in aqueous micellesrdquoSynlett no 6 pp 883ndash885 2008
[29] AM Zonouz and S B Hosseini ldquoMontmorillonite K10 clay anefficient catalyst for Hantzsch synthesis of 14-dihydropyridinederivativesrdquo Synthetic Communications vol 38 no 2 pp 290ndash296 2008
[30] A Debache R Boulcina A Belfaitah S Rhouati and BCarboni ldquoOne-pot synthesis of 14-dihydropyridines via aphenylboronic acid catalyzed Hantzsch three-component reac-tionrdquo Synlett no 4 pp 509ndash512 2008
[31] M M Heravi F K Behbahani H A Oskooie and R H ShoarldquoCatalytic aromatization of Hantzsch 14-dihydropyridines byferric perchlorate in acetic acidrdquoTetrahedron Letters vol 46 no16 pp 2775ndash2777 2005
[32] H R Memarian and A Mirjafari ldquoSolid state photochemistryof 14-dihydropyridinesrdquo Bioorganic and Medicinal ChemistryLetters vol 15 no 14 pp 3423ndash3425 2005
[33] A Zarghi H Sadeghi A Fassihi M Faizi and A Shafiee ldquoSyn-thesis and calcium antagonist activity of 14-dihydropyridinescontaining phenylaminoimidazolyl substituentsrdquo Farmaco vol58 no 11 pp 1077ndash1081 2003
[34] A Dondoni A Massi and E Minghini ldquoTwo- andthree-component Hantzsch reaction using C-glycosylatedreagents Approach to the asymmetric synthesis of 14-diyhydropyridinesrdquo Synlett no 1 pp 89ndash92 2002
[35] MNasrollahzadeh Y Bayat DHabibi and SMoshaee ldquoFeCl3-
SiO2as a reusable heterogeneous catalyst for the synthesis of
5-substituted 1H-tetrazoles via [2+3] cycloaddition of nitrilesand sodium aziderdquoTetrahedron Letters vol 50 no 31 pp 4435ndash4438 2009
[36] D Habibi M Nasrollahzadeh A R Faraji and Y Bayat ldquoEffi-cient synthesis of arylaminotetrazoles in waterrdquo Tetrahedronvol 66 no 21 pp 3866ndash3870 2010
[37] M Nasrollahzadeh D Habibi Z Shahkarami and Y BayatldquoA general synthetic method for the formation of arylaminote-trazoles using natural natrolite zeolite as a new and reusableheterogeneous catalystrdquo Tetrahedron vol 65 no 51 pp 10715ndash10719 2009
catalyst for the preparation of arylaminotetrazolesrdquo SyntheticCommunications vol 40 no 21 pp 3159ndash3167 2010
[39] D Habibi and M Nasrollahzadeh ldquoSynthesis of arylaminote-trazoles by ZnCl
2AlCl
3silica as an efficient heterogeneous
catalystrdquo Monatshefte fur Chemie vol 143 no 6 pp 925ndash9302012
[40] DHabibiMNasrollahzadeh and T A Kamali ldquoGreen synthe-sis of the 1-substituted 1H-1234-tetrazoles by application of theNatrolite zeolite as a new and reusable heterogeneous catalystrdquoGreen Chemistry vol 13 no 12 pp 3499ndash3504 2011
[41] D Habibi and M Nasrollahzadeh ldquoZnO as an effectiveand reusable heterogeneous catalyst for the synthesis ofary-laminotetrazolesrdquo Synthetic Communications vol 42 pp 2023ndash2032 2012
![One-step synthesis of pyridines and dihydropyridines in a … · 2013-09-30 · tion of benzyl alcohol oxidation [27], the esterification of benzoic acid in a microwave tubular flow](https://static.documents.pub/doc/80x56/5e904433c4617d5874147025/one-step-synthesis-of-pyridines-and-dihydropyridines-in-a-2013-09-30-tion-of-benzyl.jpg)
