One pot synthesis of formyl phenyl terpyridine: A simplified synthesis

Article abstract of DOI:10.13005/ojc/320253

Formyl phenylterpyridinewas synthesized from methyl phenylterpyridine using SeO₂ as the oxidizing agent. SeO₂ conventionally has been used to oxidize allylic and aliphatic methyl groups. The simple conversion of methyl group attached

Full text of DOI:10.13005/ojc/320253

ISSN: 0970-020 X
CODEN: OJCHEG
016, Vol. 32, No. (2):
Pg. 1261-1264
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
2
www.orientjchem.org
One Pot Synthesis of Formyl Phenyl
Terpyridine: A Simplified Synthesis
ANUP GURUNG and SANJAY DAHAL*
Department of Chemistry, Sikkim Manipal Institute of Technology,
Sikkim Manipal University, East Sikkim- 737136, India.
*
Corresponding author E-mail: dahal.sanjay@smit.smu.edu.in
http://dx.doi.org/10.13005/ojc/320253
(Received: February 29, 2016; Accepted: April 02, 2016)
ABSTRACT
Formyl phenylterpyridinewas synthesized from methyl phenylterpyridine using SeO as the
2
oxidizing agent. SeO conventionally has been used to oxidize allylic and aliphatic methyl groups.
2
The simple conversion of methyl group attached to aromatic ring appended to heterocycle in a
clean one pot synthesis paves way for synthesis of similar aldehydes extendable to other classes
of compound as well.
Keywords: Methyl phenylterpyridine (4-methyl-phenyl-2,2’:6’,2’’-terpyridine),
Formylphenylterpyridine(4-formyl-phenyl-2,2’:6’,2’’-terpyridine)”, Oxidation, Selenium dioxide.
7
INTRODUCTION
of the reactions . Mild oxidizing agents has been
used to oxidize methyl group to alcohol. Variety of
reagents convert methyl group to aldehyde.Methods
like Etard reaction, chromyl chloride oxidation and
oxidation with PCC involve multistep reactions for
Aldehydes are the versatile reagents in the
organic synthesis and especially aromatic aldehydes
has been extensively used as a starting reagent for
various products through various types of reactions
8-11
conversion . CeriumandIridiumcatalyzedreaction
can oxidize methyl group attached to aromatic group
1
-4
.
Synthesis of Oximes which are known for their
1
2-15
biological activity from aldehydes has been reported
like benzene
but is not successful in oxidizing
5
in the literature . Recently the synthesis of aryl
methyl groups attached to heterocyclic rings.
Selenium dioxide is a versatile reagent for oxidizing
methyl groups directly attached to heterocyclic ring
like 3-methylbipyridine, 4-methylphenantrholine,
2,5-dimethylpyridine .Heterocyclic aldehydes are
best known for their versatility in the synthesis of
amines from aldehydes which has pharmaceutical
importance has been reported using Zn(BH ) /
MgBr .Varieties of oxidizing agents are available for
oxidation of aliphatic as well as aromatic alkyl groups
which gets converted to carboxylic group in majority
4
2
6
2
1
6

1
262
GURUNG & DAHAL. Orient. J. Chem., Vol. 32(2), 1261-1264 (2016)
Yield %- 60%, HNMR-(CDCl , 400 MHz,
biologically active molecules.But the problem arises
3
when there is a aromatic ring like phenyl ring present ppm) 2.4 (s, 3 H) d 7.49 (m,2 H), 8.01 (m, 2 H), 8.15
in between heterocycle and the methyl group.Almost (m, 4H), 8.72 (d,2 H), 8.80 (d, 2 H), 8.98 (s, 2 H),.5,
all the reported methods failed to oxidise such methyl UV-Vis- 281 nm
groups.Schubert et al.reported the oxidation of such
1
7,18
methyl group to aldehyde in a multistep process
.
Formyl phenylterpyridine[2] (FPT)
1 g (9.0 mmol) of SeO and 0.1 ml (5.55
SeO was found to be unsuccessful in oxidation of
2
2
methyl group of nitro toluene and even that of 2,4,6- mmol) of H O was added to 700 (2.16mmol) mg of
2
trinitrotoluene, however on conversion to phenyl MPT in 10 ml of 1,4-dioxane.The mixture was heated
o
bromides conversion to aldehyde was found to be at 200 C in autoclave for 2 hours.The steel bomb was
1
9
feasible . Here we report the simplified synthesis of taken out and cooled to room temperature.Additional
aldehyde (FPT) in one pot using SeO in 1,4-dioxane 1 g of SeO and 0.5 ml of H O was added and the
2
2
2
paving the way for simplified oxidation of such class steel bomb was heated in autoclave for 6 hrs. The
of compounds to aldehydes.
steel bomb was cooled to room temperature and
the pale yellow colored product formed was dried
on water bath. The product was purified by column
chromatography using CHCl and 9:1 CHCl :MeOH
EXPERIMENTAL
3
3
Methyl phenyl terpyridine [1] (MPT)
mixture as the eluent.
waspreparedusingKrohnkemethodologyby
condensation of 2-acetyl pyridine and p-tolualdehyde
1
Yield - 20%, HNMR (CDC , 400 MHz, ppm)
l3
in 60% yield. 1.65 g (41 mmol) of crushed NaOH d 7.39 (m,2 H), 7.91 (m, 2 H), 8.05 (m, 4H), 8.69 (d,
was added to the 30ml of Polyethylene Glycol (PEG- 2 H), 8.75 (d, 2 H), 8.78 (s, 2 H), 10.12 (s, 1 H).5,
3
(
1
00) with constant stirring at room temperature. 5 g UV-Vis, 283 nm.
41.6mmol) of 2-acetyl pyridine was added and after
0 minutes 2.472 g (20.6 mmol) of p- tolualdehyde
RESULT AND DISCUSSION
was added with continuous stirring. The colorless
solution turned to light yellow. After two hours the
Several reactions were carried out using
color changed to orange and then to pink. 25 ml of different amount of SeO2 to obtain maximum
liquid NH (18N) was added. The white precipitate conversion.As per the Table 1. large scale synthesis
3
formed was washed with water and recrystallized of aldehyde using higher concentration failed to yield
from ethanol.
any product even after keeping the reaction mixture
Fig.1: Synthesis of Methyl Phenyl Terpyridine following Krohnke Methodology

GURUNG & DAHAL. Orient. J. Chem., Vol. 32(2), 1261-1264 (2016)
1263
Fig. 2: Autoclave synthesis of FormylPhenylTerpyridine from Methyl
PhenylTerpyridine using SeO as oxidant
2
Table 1: Standardization of the synthesis of FormylPhenyl Terpyridine
MPT
mmols
SeO2
mmols
1,4-Dioxane
ml
H O
mmols
Temp.
Time
h
Yield
%
2
o
C
6
0
0
0
2
.31
.30
.30
.30
.16
9.00
1.15
1.15 +* 1.15
1.80 +*1.80
4.50+*4.50
35
10
10
16
10
11.1
5.55
5.55+*5.55
2.77+*2.77
5.55+*5.55
120
125
125
150
200
12
12
2 +* 8
2 +*10
2+*6
0
0
10
9
20
*
Time after addition of additional amount of SeO and H 0.
2 2
O
at 120 C for 12 hours. Even in low concentration
the reaction failed and no product was detected.
Upon slight modification of the reaction condition
i.e. changing from one time addition to two time
addition of oxidizing agents after an interval resulted
in formation of desired product.It can be inferred with
ample support from literature that in the first step of
reaction the methyl group gets converted to alcohol
group which in next step gets converted to the
desired formyl group.Molar ratio of SeO :MPT:H O
tolyl group attached to heterocycle to aldehyde in
one pot synthesis which otherwise is not possible
in normal conditions. Though the conversion was
standardized with only one heterocycle it can be
easily extended to other heterocycles. 1,4-dioxane
was chosen on the basis of solublity of the initial/
reactants.
The aldehyde prepared has been
successfully used for the synthesis of porphyrin
as revealed by UV-vis spectroscopy and detailed
characterization of which is under progress.
2
2
in proportion of 3/2:1 :5 gave the best yield. Though
small amount of unreacted MPT was detected it was
reused for further reaction.The study also suggests
O
that at the optimal temperature of 200 C, the yield
ACKNOꢀLEDGEMENT
is best and the reaction time required for second
step of reaction could be reduced to 6 hours. The
method opens up the new route for the oxidation of
The authors would like to thanks the DST,
Gov. of India for financing the research with Grant
No. DST:SR/S1/IC-08/2006.

GURUNG & DAHAL. Orient. J. Chem., Vol. 32(2), 1261-1264 (2016)
1264
REFERENCES
11.
Ratcliffe,R. W. Org. Synth.;,1988,6 , 373-
375
1
2
3
4
5
6
7
.
.
.
.
.
.
.
Aspinall, H. C; Greeves, N; Valla,C., Org.
Lett.,2005, 7, 1919-1922;
Duan,X.-F.;Feng, J.-X.;Zi,G.-F;Zhang,Z.-B,
Synthesis, 2009,2, 277-282;
Takenaka,N.; Xia,G; Yamamoto,H, J. Am.
Chem. Soc., 2004, 126, 13198-13199
Corey,E. J.; Gilman,N.W.; Ganem,B., E. J.
Am. Chem. Soc.1968; 90, 5616 – 5617
Ghozlojeh, N. ;Setamidideh, D., Orient. J.
Chem.,2015, 31, 1823-1825
12.
Ho,T.L.; Mijs,W.J; de Jonge C.R.H
,Organic Synthesis by Oxidation With Metal
Compounds, Plenum, New York, 1986,
569–631.
Nair,V.; Balagopal,L.; Rajan,R. Mathew,J.;
Accounts Chem. Res.,2004,37,21–30.
Demappa, M.T., J. Appl. Polym. Sci.,2006,
103,3498–3505.
Jiang,B. ; Feng, Y. ; Ison,E.A. , J. Am. Chem.
Soc. ,2008, 130, 14462–14464
Trump,E. L.; ZhouM.X, Transactions of the
Kansas Academy of Science,1903, 96, 167-
180
13.
14.
15.
16.
Mahmoudi, M; D, Orient. J. Chem., 2015, 31,
1
215-1218
Dash S.; Patel S.; Mishra,B. K., Tetrahedron,
008, 65, 724
2
8
9
.
.
Ho,T. L.,Synthesis, 1972,7, 347-354
Hwu,J.R.;King,K.Y,Current Science,2001, 81,
17.
18.
19.
Winter,A.; Egbe,D. A. M.; SchubertU. S.,
Organic Letters, 2007, 9,2345-2348 ·
Collin, J.-P.; Heitz,V.; Sauvage, J.-P.
Tetrahedron Lett.1991, 32, 5977–5980.
Fischer,C. H. Auration of Aromatic Nitriles,
,
1043-1053
Wheeler,O.H.,Can. J. Chem. ,1958,36 , 949-
51
1
0.
9
1934,56, 2056-2057.