Indian Journal of Chemistry
Vol. 408. March 200 I , pp. 248-249
Note
~
Synthes is of dibenzo(b ,g)-5-methyl-1 ,8naphthyrid ines
UNrlOH
PCI;
POCI.\
Mazaa hir Ki dwa i* & See ma Koh li
Depart ment of Chem istry. University of Delhi. De lhi 110 007.
India
Receil'ed 26 Mav 1999: accepted (revised ) 2 February 2000
A se ri es of I ,8- naphthyridin es have been sy nthesised. 2Hydroxy-4- methy lquinoline 1 on reacti on w ith PCI 5 /POCI.1 gives
2-chloro-4-mc th ylqu inoline 2 whi ch on trea tmen t with substituted
:mi lines yields 2-q uinol inam ines 3a-e. Cyc !isati on in situ affords
the titl e compounds 4a-e using phosphoru s oxychloride and
dimethy l formam idc.
Earli er I ,8-naphthyri dines were sy nthes ised startin g
from 2-amino- ni cotinaldehyde via Friedlander
co ndensation 1•3 • In th e present work altern ate route fo r
the sy nthes is of I ,8-naphthyridin es fro m 2-hydroxy-4meth ylquinoline has been di scussed. Quinoline
de riva ti ves~- 7 , quinolinamines 8- 11 and I ,8-naphthyri dines 12 - 15 are pharmaco logically important. So, these
moieties att ract co nsi derable attention as potenti al
bioactive agents and prompted us to sy nthesize a
series of I ,8- naphthyridines.
2-H yd roxy-4- methylquinoline was obtained by th e
cyc lisati on of acetoacetani Iide 16 whi ch on treatment
with POCI:/ PCI5 gave 2-chl oro-4-methylquinoline 5 .
Thi s on treatment with substituted anilines afforded 2quinolinamines 3a-e. In IR spectra a peak appeared in
the region 3250-3350 cm-1 due to NH and at 8 9.5 in
1
H NMR spectra. Compounds 3a-e on reacti on with
phosphorous oxychl oride and dimeth yl formamide
gave substituted naphth yridines 4a-e whi ch were
ev idenced by disappearance of peak du e to NH in IR
and 1 H NMR spectra. The reaction route is shown in
Scheme I and the charac teri zati on data of 3a-e and
4a-e are given in Tables I and II respecti ve ly.
Experimental Section
Melting points were taken on Thomas Hoover
apparatus and are un corrected. IR spectra were
recorded on a Perkin- Elmer FTIR spectrophotometer
using KBr di scs and 1H NMR on aFT NMR Hitachi
R-600 using Me4 Si as intern al stand ard (c hemi cal
shi fts in 8, ppm). The purity of th e compoun ds were
chec ked on sili ca gel coated AI plates (Merck).
General procedure for the synthesis of 2aryl(alkyl)aminoquinolines 3a-e. A mi xture of 2-
4a·o
J a-e
a. R =H
b. R =p- 0 :
c. R =2-CI, 3- F
d. R =p-OCJ-t.
c. R =o-OCH,
Table I Compel
Scheme I
Characterizati on data of compounds 3a-e
1
mp
oc
Yi eld
(%)
1-1 NM R
3a
120-2 1
70
2.58 (s, 3H, 4-CH 3 ), 6.40 (s, I H,
H-3), 7.20-7.60 (m, 9H, Ar- H), 9.50
(brs, I H, N H)
31>
222
72
2.40 (s, 3H, 4-Cl-1 3 ) , 6.35 (s. I H.
H-3), 7.2-7.8 (m, 8H. Ar- H). 9.50
(brs, I H, N H)
3c
180
68
2.40 (s, 3H. 4-CH.J). 6.38 (s, I H.
H-3), 7.2-7.8 (m, 71-1. Ar-H). 9.52
(brs. I H, N H)
3d
142-43
75
2.40 (s, 3H. 4-CH.J ), 3.73 (s, 3H,
OC H 3 ), 6.40 (s, I H. H-3), 7.1 -7.7
(m . 81-1, A r-H), 9.50 (brs, I H. NH)
3e
148
72
2.4 1 (s, 31-1 , 4-C l-1 1). 3.70 (s, 31-1.
OC H 3) , 6.38 (s, I H. H-3), 7.1 -7.7
(m, 81-1, Ar-1-1). 9.6 (brs. I H. NH)
chloro-4- methylquinoline 2 (0.01 mole) and approp riate
aniline (0.0 I mole) in bu tanol ( 15 mL) was stitTed at
reflu x temperature. The reacti on was moni tored by
TLC and stopped when starting materi al had
disappeared. The prec tpttate was collected by
filtrati on, was hed with ethanol, dried i11 vacuo and
recrystalli sed fro m acetone.
General procedure for synthesis of dibenzo(b,g)5-methyl-1, 8-naphthyridines 4a-e. A mi xture of
quin olinamines 3a-e ( 1.38 mmole), phosphoryl
chloride (8.28 mmole) and dimeth yl fo rmamide ( 15
mL) was heated in an oil -bath with stirrin g. On
co mpleti on of reactio n, the reacti on mixtu re was
poured in water and neutralized with sod iu m
NOTES
Table I I - C ha ract e ri za ti o n data of co mp o und s 4a-e
Compel
mp
oc
Yield
1
HNMR
(%)
4a
2 15
65
2.40 (s, 3H, 4-CH 3), 7.2-7.60 (m,
8H, Ar- H), 8.5 (s. I H, 4-H)
4b
220
68
2.40 (s, 3H, 4-CH 3) , 7.2-7.8 (m, 7H ,
Ar-H), 8.4 (s, I H. 4- H)
4c
240
70
2.42 (s, 3H, 4-CH3). 7.1-7.7 (m, 6H.
Ar-H), 8.38 (s, I H, 4-H)
4d
158
65
2.45 (s, 3H, 4-CH , ), 3.70 (s, 3H.
OCH 3), 7.1-7.6 (m, 7H , Ar-H). 8.35
(s, I H, 4-H)
4e
182
67
2.40 (s, 3H, 4-C H3 ), 3.70 (s, 3H.
OC H3), 7.0-7.5 (m. 7H , ArH), 8.30
(s, I H, 4-H)
bicarbonate. Th e so lid obtain ed was filtered off,
washed with water and recrystallised from ethan ol.
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