An efficient Friedlander condensation using sodium fluoride as catalyst in the solid state

Article abstract of DOI:10.1081/SCC-120023427

Sodium fluoride catalyzed Friedlander condensation of 2-amino-nicotinaldehye with various carbonyl compounds containing α-methylene group in the solid state furnished corresponding 1,8-naphthyridines. The reaction proceeds efficiently at room temperature

Full text of DOI:10.1081/SCC-120023427

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An Efficient Friedlander Condensation Using Sodium
Fluoride as Catalyst in the Solid State
K. Mogilaiah a & Ch. Srinivas Reddy a
a Department of Chemistry, Kakatiya University, Warangal, India
Version of record first published: 17 Aug 2006
To cite this article: K. Mogilaiah & Ch. Srinivas Reddy (2003): An Efficient Friedlander Condensation Using Sodium Fluoride as
Catalyst in the Solid State, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 33:18, 3131-3134
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 18, pp. 3131–3134, 2003
An Efficient Friedlander Condensation Using
Sodium Fluoride as Catalyst in the Solid State
*
K. Mogilaiah and Ch. Srinivas Reddy
Department of Chemistry,
Kakatiya University, Warangal, India
ABSTRACT
Sodiumfluoride catalyzed Friedlander condensation of 2-amino-
nicotinaldehye with various carbonyl compounds containing
a-methylene group in the solid state furnished corresponding
1,8-naphthyridines. The reaction proceeds efficiently at room
temperature in high yields and in a state of excellent purity.
Key Words:
*Correspondence: K. Mogilaiah, Department of Chemistry, Kakatiya
University, Warangal 506 009, India; E-mail: mogilaiah_k@yahoo.com.
3131
DOI: 10.1081/SCC-120023427
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3132
Mogilaiah and Reddy
Friedlander synthesis[1–3] is an acid or base catalyzed condensation
followed by a cyclodehydration between an aromatic 2-aminoaldehyde or
ketone with the carbonyl compound containing a reactive a-methylene
group. 2-Aminonicotin-aldehyde condense readily with active methylene
compounds in the presence of base[4] or acid[5] catalysts. However, these
methods suffer harsh reaction conditions and longer reaction time.
Therefore, it is important to develop a simple and environmentally
safe, solvent free method to synthesis 1,8-naphthyridine derivatives.
In recent years organic reactions in the solid state have been attracting
the synthetic organic chemists because of their simplicity and synthetic
value.[6–9] Furthermore, the solid state reaction has many advantages:
reduced pollution, low costs, and simplicity in process and handling.
In view of this and in continuation of our interest on solid state organic
reactions,[10–13] herein, we wish to report NaF catalyzed Friedlander
condensation in the solid state at roomtemperature.
The Friedlander condensation of 2-aminonicotinaldehyde 1 with active
methylene compounds 2 in the presence of NaF in the solid state at room
temperature results in the formation of the corresponding 1,8-naphthyri-
dines 3 in high yields (Sch. 1). The reaction is fairly general, clean, rapid, and
efficient and product isolation is easy. The high yield transformations
did not formany undesirable side products. Further, it is to be noted that
highly pure products were obtained using this simple procedure and in most
cases no further purification was needed. The process is environmentally
benign. The experimental procedure is very simple. The reaction is also
expedited by microwave irradiation. Our attempt to use NaF as catalyst
for the reactions between 2-aminonicotinaldehyde 1 and active methylene
compounds which are in liquid state under the same conditions met with
failure and further work in this direction is under progress.
To the best of our knowledge, this is the first report on rapid synth-
esis of 1,8-naphthyridine derivatives using NaF as catalyst in the solid
state at roomtemperature.
In conclusion, we have demonstrated a simple and efficient procedure
involving simple workup for the preparation of 1,8-naphthyridine deri-
vatives under solid state conditions at roomtemperature. Moreover, high
O
CHO
NH2
O
C
O
C
Ar
NaF
Solid state
+
R
CH2
Ar
N
N
N
R
2
1
3
Scheme 1.

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Efficient Friedlander Condensation
3133
Table 1. Condensation of 2-aminonicotinaldehyde 1 with active methylene
compounds 2.
M.P. (ꢀC)
Time Yield
(min) (%)
Product
R
Ar
Found Reported[14–16]
3a
3b
3c
3d
3e
3f
CH3 C6H5
C6H5 C6H5
5
8
92
88
90
92
88
90
91
94
90
93
88
89
92
91
143
161
143
160
215
170
150
150
240
205
280
278
218
277
201
210
CH3
CH3
CH3
CH3
CH3
CH3
C6H5NH
6
215
172
p-CH3C6H4NH
p-CH3OC6H4NH
o-ClC6H4NH
10
12
9
149–150
150–151
241
3g
3h
3i
m-ClC6H4NH
p-ClC6H4NH
8
8
206–207
279
278
C6H5 C6H5NH
14
11
12
12
9
3j
C6H5 p-CH3C6H4NH
C6H5 p-CH3OC6H4NH
C6H5 o-ClC6H4NH
C6H5 p-ClC6H4NH
C6H5 p-BrC6H4NH
3k
3l
217–219
278
3m
3n
201–202
211
12
yields of the products, short reaction times, availability, inexpensive and
environmentally friendly catalyst are noteworthy advantages of this.
EXPERIMENTAL
General Procedure
A mixture of 2-aminonicotinaldehyde 1 (0.01 mol), active methylene
compound 2 (0.01 mol) and NaF (0.01 mol) was ground by pestle and
mortar at room temperature for the specified time indicated in Table 1
and treated with water. The resultant solid was filtered, washed with
water and recrystallized fromappropriate solvent to give 1,8-naphthyr-
idine derivatives 3. Products were characterized by comparison with
1
authentic samples (IR, H NMR, Physical constants and TLC).
ACKNOWLEDGMENTS
The authors are thankful to the Director, IICT, Hyderabad for
1
providing H NMR spectral data.

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3134
Mogilaiah and Reddy
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Received in the USA January 15, 2003