Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 42:273–277, 2012
Copyright ꢀ Taylor & Francis Group, LLC
C
ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2011.609858
PPA-SiO2 Catalyzed One-Pot Synthesis of
1,4-Dihydropyridines Under Solvent-Free Conditions
Amir Khojastehnezhad,1 Farid Moeinpour,2 and Alireza Shams1
1Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, I. R. Iran
2Department of Chemistry, Bandar Abbas Branch, Islamic Azad University, Bandar Abbas, I. R. Iran
PPA-SiO2 has been used in some organic reactions, such
as conversion of carbonyl compounds into oxathioacetals
and dithioacetals,[18] synthesis of amidoalkyl naphthols,[19]
one-pot Knoevenagel condensation, Michael addition and
cyclo-dehydration of dimedone and aldehydes,[20] synthesis
of 2-substituted-1,2,3,4-tetrahydro-4-quinazolinones,[21] and
synthesis of 14-Aryl-14H-dibenzo[a,j]xanthenes.[22]
Silica gel–supported polyphosphoric acid (PPA-SiO2) was found
to be an efficient catalyst for the one-pot condensation reaction
of aryl aldehydes, ethyl acetoacetate, and ammonium acetate to
afford the corresponding 1,4-dihydropyridines in excellent yields.
The main advantages of the present approach are short reaction
times, clean reaction profiles, and simple experimental and work-
up procedures.
Keywords 1, 4-dihydropyridines, heterogeneous catalyst, one-pot re-
action, PPA-SiO2, silica-supported polyphosphoric acid,
solvent-free
EXPERIMENTAL
Materials and Techniques
All chemicals were commercially available and used with-
out further purification. All yields refer to isolated products
after purification. Products were characterized by comparison
of spectroscopic data (IR, 1H NMR spectra) and melting points
with authentic samples. The catalyst was synthesized according
to the literature.[18] Melting points were recorded on an elec-
trothermal type 9100 melting point apparatus. The IR spectra
were obtained on a 4300 Shimadzu spectrophotometer as KBr
disks. The 1H NMR (500 MHz) spectra were recorded on Bruker
DRX500 spectrometer in DMSO-d6 relative to TMS.
INTRODUCTION
1,4-dihydropyridines (1,4-DHPs) have received much atten-
tion because of their significant pharmaceutical and biological
activities such as antiviral, antibacterial, antihypertensive, and
antitumor effects.[1] Synthesis of 1,4-DHPs is usually completed
via one-pot Hantzsch condensation of aldehydes with ethyl ace-
toacetate, and ammonia in acetic acid, alcohol as solvent.[2]
However, this method involves long reaction time and gives
products in low yields. Recently, a number of modified methods
such as the use of microwaves,[3] ionic liquids,[4] high temper-
atures at reflux,[5] TMSCl–NaI,[6] I2,[7] SiO2-NaHSO4,[8] SiO2-
HClO4,[9] CAN,[10] Na- and Cs-Norit carbons,[11] tetrabuty-
lammonium hydrogen sulfate,[12] fermenting Baker’s yeast,[13]
organocatalysts,[14] metal triflates,[15] ultrasound irradiation,[16]
and triphenylphosphine.[17] In this context, we have found that
the Hantzsch reaction occurs very smoothly in the presence
of silica-supported polyphosphoric acid (PPA-SiO2) as a het-
erogeneous and reusable catalyst under solvent free conditions
(Scheme 1).
General Procedure for the Synthesis of
1,4-Dihydropyridines Using PPA-SiO2 as Catalyst
A mixture of ethyl acetoacetate 1 (2 mmol), aromatic alde-
hyde 2a-h (1 mmol), ammonium acetate (1.2 mmol) and PPA-
SiO2 (0.03 g) was heated on the oil bath at 100◦C for 50–75
min. The reaction was monitored by TLC. After the completion
of the reaction, the reaction mixture was cooled to room temper-
ature and hot ethanol was added. The solid residue was dissolved
in hot ethanol and filtered off. The crude product was collected
from the filtrate after cooling to room temperature and recrys-
tallized from ethanol to give compounds 3a-h in high yields. All
of the 1,4-DHPs are known and were identified by comparison
of their physical and spectroscopic data (IR, NMR) with those
of authentic samples.[16,17]
PPA-SiO2 is safe, easy to handle, and environmentally
benign with fewer disposal problems. PPA-SiO2 was prepared
from the reaction of silica gel with polyphosphoric acid.[18]
Physical and spectroscopic data of the representative product
are given below:
Received 23 April 2011; accepted 29 July 2011.
For Diethyl 2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydro-
Address correspondence to Amir Khojastehnezhad, Department of
Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, I. R.
Iran. E-mail: akhojastehnezhad@yahoo.com
1
pyridine-3,5-dicarboxylate (3h): m.p. 129–132◦C; H NMR
(DMSO-d6, 500 MHz): δ: 1.11 (t, 6H, J = 8.5Hz); 2.30
273