Novel and efficient method for the synthesis of 4-chloro-5, 6-dihydro pyran derivatives using Lewis acidic chloroaluminate ionic liquids

Article abstract of DOI:10.13005/ojc/320459

The reaction of aldehydes/ketones with homopropargylic alcohols in the presence of 1-n-Butyl-3-methylimidazolium chloroaluminate [bmim]Cl·AlCl₃ (N = 0.56-0.67) ionic liquid generates the 4-chloro-5,6-dihydro-2H-pyran derivatives in excellent yi

Full text of DOI:10.13005/ojc/320459

ISSN: 0970-020 X
CODEN: OJCHEG
2016, Vol. 32, No. (4):
Pg. 2259-2262
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
Novel and Efficient Method for the Synthesis of
4-Chloro-5, 6-dihydro Pyran Derivatives using
Lewis Acidic Chloroaluminate Ionic Liquids
N. MARUTHI RAJU2,3, K. RAJASEKHAR1*,
J. MOSES BABU2 and B. VENKATESwARA RAO3
1Ragas Pharmaceuticals Private Limited (OPC), IDA Cherlapally, Hyderabad, 500051, India.
2Custom Pharmaceutical Services, Dr Reddy’s Laboratories Limited,
Bollaram Road, Miyapur, Hyderabad, 500049, India.
3Department of Organic Chemistry, Foods, Drugs and Water,
Andhra University, Visakhapatnam, 530003, India.
*Corresponding author E-mail: koorella.rajasekhar@gmail.com
http://dx.doi.org/10.13005/ojc/320459
(Received: May 30, 2016; Accepted: August 07, 2016)
ABSTRACT
The reaction of aldehydes/ketones with homopropargylic alcohols in the presence of 1-n-
Butyl-3-methylimidazolium chloroaluminate [bmim]Cl·AlCl3 (N = 0.56-0.67) ionic liquid generates the
4-chloro-5,6-dihydro-2H-pyran derivatives in excellent yield and in short reaction times.
Keywords: 1-n-Butyl-3-methylimidazolium chloroaluminate, Aldehydes, Ketones,
Homopropargylic alcohols, 4-chloro-5,6-dihydro-2H-pyran derivatives.
INTRODUCTION
synthetic method for the synthesis of dihydropyrans.
Although other methods were reported5, Consequent
methods that successfully minimize the use of
toxic and volatile organic solvents are the focus
of much attention. In this respect, ionic liquids are
attracting growing interest as alternative reaction
media for various chemical and biotransformations6.
In particular, choloroaluminate ionic liquids are
having Lewis acidity, which can be varied over a
wide range, and their intrinsic ability to solvate a
variety of substances.These ionic liquids are easily
prepared from AlCl3 and 1-butyl-3-methylimidazolium
chloride. These chloroaluminate ionic liquids have
Substituted dihydropyrans are the key
intermediates for the synthesis of many natural
products1.Many natural products like Swinholides2a,
Laulimalides2b, Ambruticins2c and Jerangolids2d
contains dihydropyran skeleton. Moreover, the
olefin function is having synthetic value for further
functionalization in obtaining polysubstituted
tetrahydropyrans3. The coupling of alkynes to
aldehydes is an important transformation in organic
synthesis4.The direct synthesis of dihydropyrans by
thecouplingofalkynestoaldehydesprovidesauseful

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RAJU et al., Orient. J. Chem., Vol. 32(4), 2259-2262 (2016)
the advantage of being liquid at room temperature
over a considerable composition range of apparent
mol fraction of AlCl3 (N = 0.30-0.67) and also
RESULTS AND DISCUSSION
Inviewoftheemergingimportanceoftheuse
have negligible vapour pressures, making them of Ionic liquids as cost-effective and environmentally
useful alternatives to conventional molecular benign catalysts, we herein describe a simple and
organic solvents for various synthetically useful efficient protocol for the cyclization reactions of
transformations7.Furthermore, chloroaluminate ionic aldehydes and homopropargylic alcohols to produce
liquids play dual roles both as Lewis acid catalyst and dihydropyrans using 1-n-Butyl-3-methylimidazolium
as solvent.
chloroaluminate [bmim]Cl·AlCl3 (N = 0.56-0.67) ionic
liquid under mild reaction conditions (Scheme I).
Cl
O
R''
[bmim]Cl.xAlCl3
R"
+
R
R' = R" = H or Alkyl
R
1
R'
OH
r.t.
O
3
R'
2
Scheme I
Forinstancetreatmentofbenzaldehydewith with high efficiency. The reaction worked well both
3-butyn-1-ol in [bmim]Cl·AlCl3 ionic liquid afforded with aromatic, aliphatic aldehydes and ketones.
dihydropyran in 70% yield.The reaction is very clean When symmetrical ketones like cyclohexanone and
and complete within 30 sec. at room temperature. 3-pentanone reacted with 2c and 2d the formation
In a similar manner, various aldehydes and of single product was observed. But when applied to
ketones underwent smooth cyclization reaction with aldehydes the formation of a mixture of the isomers
homopropargylic alcohols to give the corresponding were observed by TLC and 1HNMR spectrum. This
dihydropyran derivatives in high yields. In all cases, is due to the formation of the diastereomers in the
the reactions proceeded readily at room temperature later case (Scheme II).
O
Mixture of isomers
[bmim]Cl.xAlCl3
r.t.
+
OH
R
H
R'
R = R' = Alkyl or Aryl
1
2
Scheme II
dihydropyran carbenium ion which is further attacked
by the chloride nucleophile to form the 4-Chloro
dihydropran derivative (Scheme III).
The mechanism for the formation of
dihydropyrans can be explained by the attack
of homopropargylic alcohol and cyclised to the
Cl
AlCl3
O
AlOCl2
Cl-
-HCl
R
R
R
+
R
R'
O
O-AlOCl2
O
R'
O
R'
O
H
R'
Scheme III

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RAJU et al., Orient. J. Chem., Vol. 32(4), 2259-2262 (2016)
Table I -
Lewis Acidic Chloroaluminate Ionic Liquid promoted synthesis of 4-chloro-5,6-dihydro pyran derivatives
Yield (%)[b]
Alcohol
Products [a]
Entry
Aldehyde/Ketone
Cl
CHO
70
73
1
Ph
O
3a
OH
OH
2a
2a
1a
Cl
2
3
4
5
CHO
O
1b
O
3b
Cl
O
CHO
68
75
O
3c
OH
OH
2b
1c
Cl
CHO
O
3d
1d
2a
Cl
66
70
CHO
OH
O
1d
2a
2a
3e
Cl
CHO
6
7
O
3f
1e
OH
OH
Cl
O
68
72
Ph
O
Ph
2c
1f
3g
Cl
O
8
9
OH
OH
O
3h
Cl
2d
1g
O
68
O
1h
3i
2d
aAll the products were characterized by 1H NMR and mass spectroscopy and compared with previously reported data.
bYields are isolated after column chromatography.
Butyl-3-methylimidazolium chloroaluminate ionic
liquidsystem.The attractive features of this process
are the mild reaction conditions, eco-friendly reagent,
short reaction times and cleaner reactions with
good yields, which makes it a useful process for the
synthesis of dihydropyran core structure.
CONCLUSION
In summary, we have described a green
protocol for the preparation of dihydropyran
derivatives through cyclization reaction of aldehydes/
ketones with homopropargylic alcohols using 1-n-

RAJU et al., Orient. J. Chem., Vol. 32(4), 2259-2262 (2016)
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Experimental Section
Chloro Aluminate Ionic liquids were
prepared as described previously8.
organic layers were dried over anhydrous Na2SO4,
concentrated in vacuo and purified by column
chromatography on silica gel (Merck, 60-120 mesh,
ethyl acetate/hexane, 2.0-8.0) to afford dihydropyran
3a. The products were characterized by IR, NMR
and mass spectroscopy. All the products 3b-i were
prepared by the same procedure.
General Procedure
To a mixture of benzaldehyde (500
mg, 4.71 mmol) and 3-butyn-1-ol (330 mg, 4.71
mmol) was added 1-n-Butyl-3-methylimidazolium
chloroaluminate (2 mL) at room temperature. The
mixture was stirred for 30 sec.and the reaction mass
was quenched with icecold water and extracted
with diethyl ether (10-15 mL). The combined
ACKNOwLEDGEMENTS
NMR thanks Dr Reddy’s Laboratories for
permitting the research work.
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