K Mogilaiah*, N Vasudeva Reddy & R Babu Rao Department...
2
Indian Joual of Chemistry Vol. 40B, September 21 , pp 837-838 Note Microwave assisted synthesis of 1,8- naphthyridines K Mogilaiah*, N Vasudeva Reddy & R Babu Rao Department of Chemistry, Kakatiya University, Warangal 5& 009, India Received 30 March 2000; accepted (ravised) JO August 2000 A highly efficient and practical methodology for the synthesis of 2-aryl -1 ,8-naphthyridines 3 is descrid starting from 2-aminonicotinaldehyde 1 and various acetophenones under microwave conditions. Novel approaches to ecofriendly chemistry demands usage of domestic microwave oven for the synthesis of heterocycles, a practically convenient, safe and rapid methodology 1. 1 ,8-Naphthyridine derivatives are reported to possess interesting pharmacological properties 5 . 7 • In view of this, we herein report a very clean, rapid and high yielding method for the preparation of 1,8-naphthyridines using microwave irradiation under solvent free conditions. Condensation of 2-aminonicotinaldehyde 1 with various acetophenones 2 in the presence of KOH without any solvent under microwave irradiation fuished 2-aryl -l,8-naphthyridines 3 in excel lent yields (Scheme I). It is noteworthy that the reaction is completed within 5 min and in the absence of a solvent. This is much superior method compared to the literature one, 8 wherein the above reactants had to be refluxed for 3 hr in ethanol and 20% KOH to give moderate yields of the products. All reactions were performed in a commercial microwave oven operating at 2450 MHz frequency. In a typical case, equimolar quantities of 2- aminonicotinaldehyde 1, acetophenone and KOH were mixed together without solvent in a 100 mL conical flask capped with a glass funnel and placed in microwave oven and irradiated for 3 min. The reaction mixture was allowed to attain room temperature, treated with cold water and filtered off. After usual work-up 2-phenyl- l ,8-naphthyridines 3a was obtained in 90% yield. The reaction is of general applicability and the different 1 ,8-naphthyridines �CHO �. + N NH2 KOH • b d 2 , p-CH 3C.H. p-CH3OC.H . p-CIC.H. p-B.H. o-HOC.H. p-HO C.H. h k m n Scheme I .� �R � 3 m-N02C.H. p-N02C.H. p-CoHsC.H. 2-CIOH, . 2-C,H.N 3,CsH.N 4-C,H.N synthesized are given in Table I. The compounds were characterized and compared with authentic samples (TLC, m.p ., JR, I H NMR and MS). The effect is not purely thermal, which is supported by the fact that when same reaction was carried out using the conventional heating mode (oi l-bath) at same final temperature and reaction time as measured in the microwave experiment, traces of products were isolated aſter the complete work-up. Reactions were faster under microwave i r radiation than under conventional heating mode at the same temperature. In conclusion, the present methodology provides a highly efficient and practical synthesis of tit le compounds with following advantages : Significant shortening of the reaction time, high yields and solvent free conditions. This is the first report on a rapid synthesis of the 1 ,8-naphthyridines where microwave technique has been utilized. Experimentral Section Melting points were taken on Cintex melting point apparatus and are uncorrected. IR spectra were recorded on a Perkin-Elmer 337 spectrophotometer using KBr discs and I H NMR spectra on a Varian Gemini 200 MHz spectrometer using Me4Si as inteal standard. Mass spectra were SC .nned on a Jeol JMS D-3 spectrometer. The purity of the compounds was checked by TLC.
Transcript of K Mogilaiah*, N Vasudeva Reddy & R Babu Rao Department...
Indian Journal of Chemistry Vol. 40B, September 2001 , pp 837-838
Note
Microwave assisted synthesis of 1 ,8-naphthyridines
K Mogilaiah*, N Vasudeva Reddy & R Babu Rao
Department of Chemistry, Kakatiya University, Warangal 506 009, India
Received 30 March 2000; accepted (ravised) JO August 2000
A highly efficient and practical methodology for the synthesis of 2-aryl- 1 ,8-naphthyridines 3 is described starting from 2-aminonicotinaldehyde 1 and various acetophenones under microwave conditions.
Novel approaches to ecofriendly chemistry demands usage of domestic microwave oven for the synthesis of heterocycles, a practically convenient, safe and rapid methodology 1-4. 1 ,8-Naphthyridine derivatives are reported to possess interesting pharmacological properties5.7• In view of this, we herein report a very clean, rapid and high yielding method for the preparation of 1 ,8-naphthyridines using microwave irradiation under solvent free conditions.
Condensation of 2-aminonicotinaldehyde 1 with various acetophenones 2 in the presence of KOH without any solvent under microwave irradiation furnished 2-aryl- l ,8-naphthyridines 3 in excellent yields (Scheme I). It is noteworthy that the reaction is completed within 5 min and in the absence of a solvent. This is much superior method compared to the literature one,8 wherein the above reactants had to be refluxed for 3 hr in ethanol and 20% KOH to give moderate yields of the products. All reactions were performed in a commercial microwave oven operating at 2450 MHz frequency.
In a typical case, equimolar quantities of 2-aminonicotinaldehyde 1, acetophenone and KOH were mixed together without solvent in a 1 00 mL conical flask capped with a glass funnel and placed in microwave oven and irradiated for 3 min. The reaction mixture was allowed to attain room temperature, treated with cold water and filtered off. After usual work-up 2-phenyl- l ,8-naphthyridines 3a was obtained in 90% yield. The reaction is of general applicability and the different 1 ,8-naphthyridines
�CHO
�.J,l + N NH2
KOH MWI
Ar • b
d
II
2
c;.H, p-CH3C.H. p-CH3OC.H. p-CIC.H. p-BrC.H. o-HOC.H. p-HOC.H.
h
k
m n
Scheme I
. � �RN'�Ar 3
m-N02C.H. p-N02C.H.
p-CoHsC.H. 2-CIOH, . 2-C,H.N 3,CsH.N 4-C,H.N
synthesized are given in Table I. The compounds were characterized and compared with authentic samples (TLC, m.p., JR, IH NMR and MS).
The effect is not purely thermal, which is supported by the fact that when same reaction was carried out using the conventional heating mode (oil-bath) at same final temperature and reaction time as measured in the microwave experiment, traces of products were isolated after the complete work-up.
Reactions were faster under microwave irradiation than under conventional heating mode at the same temperature.
In conclusion, the present methodology provides a highly efficient and practical synthesis of title compounds with following advantages : Significant shortening of the reaction time, high yields and solvent free conditions. This is the first report on a rapid synthesis of the 1 ,8-naphthyridines where microwave technique has been utilized.
Experimentral Section
Melting points were taken on Cintex melting point apparatus and are uncorrected. IR spectra were recorded on a Perkin-Elmer 337 spectrophotometer using KBr discs and IH NMR spectra on a Varian Gemini 200 MHz spectrometer using Me4Si as internal standard. Mass spectra were SCl).nned on a Jeol JMS D-300 spectrometer. The purity of the compounds was checked by TLC.
838 INDIAN J CHEM, SEC B, SEPTEMBER 2001
Table 1 - 1 ,8-Naphthyridines 3
Compd
3a 3b 3c 3d 3e 3f 3g 3h 3i 3j 3k 31
3m 3D
Reaction
period
(min) 3 4 3 4 4 3 4
2.5 2 5 5
2:5 3 3
Yield
(%)
90 96 94 97 92 90 9 1 90 88 88 89 95 93 94
General procedure for preparation of 2-aryl-1,8-naphthyridines 3. A mixture of 2-aminonicotinaldehyde (0.01 mole), appropriate acetophenone (0.01 mole) and KOH (0.0 1 mole) were mixed together without any solvent in a 100 mL conical flask capped with a glass funnel and placed in a commercial microwave oven operating at 2450 MHz frequency and irradiated for the period indicated in Table I. The reaction mixture was allowed to reach room temperature and treated with cold water. The solid separated was filtered and recrytallized from a suitable solvent to give 3 (Table I).
Acknowledgement
The authors are thankful to the Directors, nCT, Hyderabad and CDRI, Lucknow for recording IH
m.p. Lits. m.p. Mol. formula
°C °C
1 16 1 16 CI4HION2 148 147 C 1sH 12N2
147-48 1 48 CIsH I2N20 202-03 202 C I4H9N2CI
2 1 6 2 1 7 CI4H9N2Br 1 88 1 88 CI4HION2O
254-55 254 C I4HION2O 2 19 2 19 C I4H9N)02
262-64 263 CI4H9N)02 1 86 1 86 C2oH I4N2 165 1 65 CIsHI2N2
147-48 148 CI3H9N) 142 142 CI3H9N)
167-68 168 C13H9N3
NMR and mass specra, respectively. One of them (NVR) is thankful to the CSIR, New Delhi for the award of a senior research fellowship.
References
1 Caddick S, Tetrahedron, 5 1 , 1995, 10403. 2 Kidwai M & Kumar P, J Chern Res(S), 1996, 254.
3 Kalita A H, Boruah A, Prajapati D & Sandhu J S, Indian J Chern, 37B, 1998, 10 1 .
4 Kad G L , Singh V , Kaur K P & Singh J , Indian J Chern, 37B, 1998, 1 72.
5 Gorecki D K J & Hawes E M, J Med Chern, 20, 1977, 1 24.
6 Balin G B & Tan W L, Aust J Chern, 37, 1984, 1065.
7 Ferrarini M, Cleondio M, Calderone U & Lovella G, Eur J Med Chern, 33, 1998, 383.
8 Sreenivasulu B & Reddy K V, Curr Sci, 46, 1977, 597.
