Indian Journal of Chemistry
Vol. 408. July 200 1 . pp. 6 1 9-62 1
Note
Hypervalent iodine mediated solid state
synthesis of 1 ,8-naphthyridinyl- l ,3,4oxadiazoles
K Mogilaiah* & P Raghotham Reddy
Dcpartmcnt of Chemistry. Kakatiya University
Warangal 506 009. India
Received 25 Novell/ber 1 999; accepted(revised) 8 May 2000
2-Trifluoromcthyl- I .8-naphthyridine-3-carboxylic acid aryli­
dene-hydrazides (acylhydrazones) 2 can be conveniently
converted to the corresponding 5-aryl-2-(2-trifluoromethyl - I .8naphthyridin-3-yl)-1 .3.4-oxadiazoles 3 with iodobenzene diacetate
(lBD) under solid state conditions. The reaction proceeds
efficiently giving the products in excellent yields at ambient
temperature.
The subject of organic solid state reactivity is a
fascinating one. Besides being of great academic
interest the exciting classes of chemical reactions
belonging to this field are also expected to be of
synthetic value l •2 • Hypervalent iodine reagents have
received considerable attention in the recent years due
to their applications
in the synthesis of heterocyclic
compounds3.6. Oxidation of acylhydrazones to 1 ,3,4oxadiazoles is an important organic transformation
from both synthetic and biochemical point of view7 .
Several reagents are documented on the literature to
effect this conversion, however these reagents suffer
from certain drawbacks such as usage of toxic
reagents like LTA, long reaction periods at high
temperature and cumbersome work-up procedu �es 8 . In
view of this and in continuation of earlier work on
solid state organic reactions9 , we report herein a new
facile method for the transformation of
acylhydrazones to 1 ,3,4-oxadiazoles in the solid state
at room temperature.
The starting compounds, 2-trifluoromethyl- I ,8naphthyridine-3-carboxylic acid arylidenehydrazides
(acylhydrazones) 2 were prepared by the
condensation of 2-tri fluoromethy 1-1 ,8-naphthyridine3-carboxylic acid hydrazide 1 with aromatic
aldehydes l O. The oxidative cyclization of
acylhydrazones 2 with IBO in the solid state at room
temperature resulted in the formation of 5-aryl-2-(2trifluoromethyl- l , 8-naphthyridin-3-yl)- I , 3, 4-oxadia
zoles 3 in excellent yields. The reaction is fairly
general, very facile, quick and efficient and is devoid
of any side-products.
In a typical case, when an equimolar mixture of
acyl hydrazone 2a (Ar = C6HS) and IBO was ground
by pestile and mortar at room temperature for 30 min,
the mixture turned to a pale-yellow solid. The solid
was treated with ice-cold water and filtered off. After
usual work-up 5-phenyl-2-(2-trifluoromethyl- I ,8naphthyridin-3-yl)-1 ,3,4-oxadiazole 3a was obtained
in 84% yield without the formation of any side­
products. Its IR spectrum exhibited absorption peaks
at 1 600 and 1 220 cm· 1 due to C=N and C-O-C
functions, respectively. The I H NMR spectrum in
OMSO-d6 showed signals at 8 8.4 (m, I H, C4 -H), 9.0
(m, I H, Cs -H), 8. 1 (m, I H, C6-H), 9.3 (m, I H, CrH)
and 7.4-7.8 (m, 5H, Ar-H). In MS the M+ peak
appeared at mlz 342 (73.5%). Other intense ions
appeared at mlz 285 ( 1 6%), 265 (16.3), 223 (54.8),
1 97 (23), 105 ( 1 00), 1 02 (29.8) and 77 (44.8).
The generality of this facile transformation was
established by treating other acylhydrazones 2b-h
with lBO, under solid state conditions to get the
corresponding I ,8-naphthyridinyl- 1 ,3,4-oxadiazoles
3b-h in high yields (Scheme I, Table I).
GCC
/'
�
I
tf
-......:::
GCC
-......:::
/'
o
C-NHNH2
CF3
A_
O
_
r-C
_H
_
_
.
�
0
I
�
2
1
C-NHN=CH -Ar
CF3
PhJ(OAc)z solid state
3
(Ar)
a = C6HS
e = o-OHC6H.
b = p-CH3C6H.
f = P-(CH3hNC6H.
c =
d
=
p-CH30C6H.
g = p-N02C6H.
p-CIC6H.
h = 3,4-(0-CH2-0)C6H3
Scheme I
620
INDIAN J CHEM, SEC 8 JULY 2001
Table I
-
Characterization data of compounds 3
Found (%) (Calcd)
Compd
Reaction
period (min)
mp
°C
Yield
(%)
Mol. Formula
(Mol. WI.)
3a
30
244
84
C17H9N4OF3
C
59.86
H
2.75
N
1 6.48
(342)
(59.65
2.63
1 6.37)
3b
3c
3d
3c
3f
3g
3h
20
15
25
22
20
12
25
238
240
1 85
1 65
1 75
263
230
96
92
94
88
90
85
89
In conclusion, we have developed an efficient and
high yield method for the conversion of
acylhydrazones to 1 ,3,4-oxadiazoles. This method has
the additional advantages of mild conditions, easy to
set-up and easy work-up, inexpensive and minimum
environmental impact. Also, this new method of
1 ,3,4-oxadiazole formation without any solvent offers
significant improvements over the existing procedures
and will make a useful and important addition to the
present methodologies.
Antimicrobial activity
All the compounds reported in Table I were
screened for their antibacterial and antifungal
activities following the filter paper disc method I I at
400 and 600 Ilg/disc concentrations using gram­
negative bacteria Escherichia coli and Pseudomonas
aeruginosa and gram-positive bacteria Bacillus
subtilis and Bacillus mycoides. The antifungal testing
was carried out against Curvalaria lunata and
Fusarium oxysporum. The activity was compared
with known standards streptomycin and carbendazim
for antibacterial and antifungal activity, respectively.
From the screening results, it was evident that all
compounds 3 exhibited moderate activity against
different strains of bacteria (zone of inhibition 6-1 ]
mm), while none of the compounds was significantly
active towards the fungi tested.
CisHI IN40F3
60.52
3.01
1 5.85
(356)
(60.67
3.09
1 5.73)
C isH I I N402F3
58.22
2.90
15.13
(372)
(58.06
2.96
15.05)
C17HgN4OCIF3
54.38
2. 1 8
14.72
(376.5)
(54. 1 8
2. 1 2
14.87)
C17H9N402F3
56.74
2.60
1 5.76
(358)
(56.98
2.5 1
15.64)
C I9H I4NsOF3
59.41
3.70
1 8.27
(385)
(59.22
3.64
1 8. 1 8)
C 17HgNs03F3
52.53
2.0 1
18.16
(387)
(52.7 1
2.07
1 8.09)
CIgH9N403F3
55.78
2.38
14.62
(386)
(55.96
2.33
1 4.5 1 )
Experimental Section
Melting points are uncorrected and were taken on a
Cintex melting point apparatus. IR spectra were
recorded in KBr discs on a Perkin-Elmer 337
spectrophotometer; mass spectra on a Jeol JMS 0-300
spectrometer at 70 e V; I H NMR spectra on a Varian
Gemini 200 MHz spectrometer using TMS as internal
standard. TLC plates were prepared with silica gel G
and spots were visualised with h vapours.
Iodobenzene diacetate (IBD) was prepared according
to 1·Iterature proced ure P- .
General procedure for the oxidation of
acylhydrazones 2 to 1,3,4-oxadiazoles 3. A mixture
of appropriate acyl hydrazone 2 (0.01 mole) and IBD
(0.01 mole) was ground by pestile and mortar at room
temperature for the period indicated in Table I and
treated with water. The resultant pale-yellow solid
was filtered and recrystallized from methanol to
afford 3 (Table I).
Acknowledgement
The authors are thankful to the Director, CDRI,
Lucknow for providing I H NMR and mass spectra.
References
1 Toda F, Synlett (Account), 1993, 303.
2 Toda F, Acc Chern Res. 28, 1995, 480.
3 Rui-yang & Li-xin Dai, J Org Chern. 58, 1993, 338 1 .
NOTES
4 Prakash 0, Saini N & Sharma P K, Synlett (Account), 1994,
22 1 .
5 Moriarty R M & Prakash 0, Adv Heterocycl Chern, 69, 1998,
I.
6 Prakash 0, Sharma V , Batra H, Rani N, Sharma P K & Singh
S P, Indian J Chern, 37B, 1998, 797.
7 Sinnur K H, Siddappa S, Hiremath S P & Purohit M G,
Indian J Chem, 25B, 1986, 7 1 6.
62 1
8 Baltazzi E & Wysocki A, J Chern Ind (London), 1963, 1080.
9 Mogilaiah K & Rao R B, Indian J Chern, 38B, 1999, 869.
1 0 Mogilaiah K, Rao R B & Reddy K N, Indian J Chern, 38B,
1999, 8 1 8.
1 1 Vincent J C & Vincent H W, Proc Soc Exptl Bioi Med, 55,
1944, 1 62.
1 2 Vogel A I , Textbook of practical organic chemistry, (ELBS
and Longman, London), 1996, p. 869.