introduction to 1,8-naphthyridines -...
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CHAPTER-I PART-C
Introduction
to
1,8-Naphthyridines
Introduction to 1,8-Naphthyridines
50
1. 1, 8-NAPHTHYRIDINES
Naphthyridine is the name commonly given to the fused-ring system
resulting from the fusion of two pyridine rings through two adjacent carbon
atoms, each ring thus containing only one nitrogen atom. The first
naphthyridine derivative was obtained and named by Arnold Reissert 18931 as
the pyridine like analogue to naphthalene. There are six different types of
naphthyridines which are defined through the position of the nitrogen atoms in
the bicyclic system (1-6).
N
N
N
N
N
N
N N
N
N
N N
1 2 3
4 5 6
1,5-Napthyridine 1,6-Napthyridine 1,7-Napthyridine
1,8-Napthyridine 2,6-Napthyridine 2,7-Napthyridine
The first unsubstituted naphthyridines synthesized, 1,5-naphthyridine2
and 1,8-naphthyridine3
were published in 1927 by Bobranski, Suchard and
Koller. 1,6-Naphthyridine, 1,7-naphthyridine and 2,7-naphthyridine were
reported by Ikekawa in 1958.4
2,6-Naphthyridine was independently reported
by Gicacomello et al and Tan et al in 1965.5
Among different types of naphthyridines, 1,8-naphthyridine derivatives
have received significant attention due to their exceptionally broad spectrum
of biological activity. The 1,8-naphthyridine skeleton is present in many
Introduction to 1,8-Naphthyridines
51
compounds that have been isolated from natural substances, with wide
spectrum of biological activities such as antibacterial,6-8
antimycobacterial,9
antitumor,10
anti-inflammatory,11
antiplatelet,12,13
gastric antisecretary,14
antiallergic,15
local anaesthetic,16
anti-HIV,17
anticancer,18
and benzodiazepine
receptor activity.19
Nalidixic acid (7), for example, possesses strong
antibacterial activity and used mainly for the treatment of urinary tract
infections with gram negative pathogens.20
In addition, Gemifloxacin (8) is an
oral broad-spectrum quinolone antibacterial agent used in the treatment of
acute bacterial exacerbation of chronic bronchitis and mild-to-
moderate pneumonia.21
One recent study showed that Gemifloxacin possess
anti-metastatic activities against breast cancer in vitro and in vivo (in mice).22
It is known that (E)- and (Z)-O-(diethylamino)ethyl oximes of 1,8-
naphthyridine series (9) are potential drugs for local anaesthesia23
and 1-(2-
fluorobenzyl)-3-(2-tolyl)-1,8-naphthyridin-2(1H)-one (10) is used for the
treatment of memory disorders, in particular, Alzheimer’s disease.24
2-Amino-
N-hydroxy-1,8-naphthyridine-3-carboxamidine (11) possesses herbicidal
properties and used for the selective control of weeds in barley, wheat, maize,
sorghum and rice crops.25
N N
C2H5
H3C
COOH
O
7
N N
COOH
O
F
H2N
H3CON
8
N NH
R2
R1
NOCH2CHEt2
9
10 11
N N
NH
NH
HO
H2N
N N
F
O
Introduction to 1,8-Naphthyridines
52
1,8-Naphthyridine derivatives also react with adenosine receptors of
subtypes A1 and A2A.26
The important biological properties just described
stimulated studies on the synthesis of various functionalized (particularly, at
positions 2, 4 and 7) 1,8-naphthyridine derivatives, with the goal of designing
new drugs for oral administration. In addition, 4-(N-
methylenecycloalkylamino)-1,8-naphthyridine derivatives substitution in
positions 2 and 7 are effective as antihypertensive agents.27
7-Amino-2-(4-carbethoxypiperazin-1-yl)-4-phenyl-1,8-naphthyridine
has recently been synthesized and reported to have marked activity against
mycobacterium tuberculosis.28
A survey of the literature shows that the major synthetic approach that
are used to prepare various types of 1,8-naphthyridine system involves
condensation of 2-aminopyridine derivatives with carbonyl compounds
containing active methylene group, aldehydes, acyclic and cyclic ketones or
diketones group in the presence of an acid or base catalyst.29-35
2. Synthesis of 1,8-naphthyridine nucleus:
Synthesis of 1,8-naphthyridines may be done by cyclisation of appropriate
aliphatic substrates, with or without auxiliary synthons, by cyclisation of
appropriate substituted pyridines with or without synthons or from other
heterocyclic substrates by several process.
a) 5-Methyl-3-(m-tolylethynyl)-2-pyridinamine (12) on treatment with sodium
ethoxide in the presence of ethanol on cyclisation produced 4-ethoxy-6-
methyl-2-m-tolyl-1,8-naphthyridine(13).36
Introduction to 1,8-Naphthyridines
53
a) 3-(2-Ethoxycarbonylvinyl)-2-pyridinamine (14) on treatment with sodium
ethoxide underwent cyclisation to form 1,8-naphthyridin-2(1H)-one (7) in
ethanol (15)37
.
N NH2
O
C2H5ONa
12 13
N N
OC2H5
N NH2
OC2H5
O
C2H5ONa
14 15
N NH
O
b) 2,5-Bis-(3-aminopropyl)pyridine (16) on treatment with NaNH2 in toluene
after cyclisation gave 2-(3-aminopropyl)-1,2,3,4-tetrahydro-1,8-
naphthyridine (17)38
. 6-(2-acetyl-1-methylethylidene) amino-2-
pyridinamine (18) gives 5,7-dimethyl-1,8-naphthyridin-2-amine (19) after
cyclisation on treatment with NaNH2 in presence of phosphoric acid at
100oC.
39
16 17
NH
NNH2
N N
18 19
N N
NNH2
H2N NaNH2
NaNH2
COCH3
H2NH2N
Introduction to 1,8-Naphthyridines
54
c. 3-(2-Nitrovinyl)-2-pyridinamine (20) underwent condensation with
benzaldehyde in xylene and gave 3-nitro-2-phenyl-1,8-naphthyridine (21)40
.
2-Pyridinamine (22) on treatment with benzaldehyde and subsequently with
acetic acid produced 2-phenyl-1,8-naphthyridine-4-carboxylic acid (23) in
ethanol41
.
20 21
N N C6H5
N NH2
22 23
N N Ph
N NH2
C6H5CHO
COOH
NO2 NO2
C6H5CHO
CH3COOH
2-Amino-3-pyridinecarbonitrile (24) on treatment with m-chlorobenzyl
cyanide, KOH/H2O on microwave irradiation produced 3-m-chlorophenyl-1,8-
naphthyridin-2-amine (25).42
The same substrate (24) with ethyl cyanoacetate
in ethanol and trace amounts of piperidine gave 2-oxo-1,2-dihydro-1,8-
naphthyridine-3-carbonitrile (26)43
.
25
N N NH2
N NH2
24
N NH
O
CNCH2COOC2H5CHO CN
26
m-chlorobenzyl cyanide
Cl
Introduction to 1,8-Naphthyridines
55
e) Niementowski synthesis:
In the first route Hitherto44
described was an extension of the
Niementowski synthesis to the preparation of 1,8-napthyridine-2,4-diols.
7-phenyl-1,8-napthyridine-2,4-diols (28) by the condensation of ethyl-2-
amino-6-phenyl nicotinate (27) with simple esters in the presence of sodium.
N NH2
27
N N OH
COOC2H5R
28
R-CH2-COOC2H5
OH
C6H5C6H5
Na
f) Friedlander synthesis:
In the second route Friedlander was described the synthesis of 1,8-
naphthyridine derivatives containing phosphorus.45
The first 2, 3 substituted
1,8-naphthyridine (31) bearing a phosphorus moiety have been synthesized by
the Friedlander annulations of 2-aminonicotinaldehyde (29) with diphenyl
phosphoryl cyclopentanones (30).
N NH2
29
N N
CHO
30O
P
R Ph
Ph
X
P
Ph
PhX31
The Friedlander condensation of 2-amino nicotinaldehyde with active
methylene compounds in the presence of catalyst lithium chloride under the
two non-conventional methods like microwave irradiation and by grinding in a
mortar afforded the corresponding 1,8–naphthyridines (32).46
Both these
Introduction to 1,8-Naphthyridines
56
methodologies are attractive as they are relatively nontoxic, economical and
highly effective. The results shows that microwave procedure as slightly
superior to the solid-state methods in terms of reduced time period and better
yields.
N NH2
N N
CHO
32
CH3COCH2COC6H5
LiCl
MW
C6H5
O
g) Reductive cyclisation:
The third route was investigated for synthesis of 1,2-dihydro-2-oxo-1,8-
naphthyridine-3-carboxylic acid (34) by reductive cyclization of diethyl 2-((2-
nitropyridin-3-yl)methylene)malonate (33).47
N NO2N N
H
O
34
OH
OCOOC2H5
COOC2H5
33
h) Recent Literature:
TABO (1,3,3-trimethyl-6-azabicyclo[3.2.1]octane) is a highly reactive
and regioselective catalyst for the preparation of 2-substituted-1,8-
naphthyridines (35) from unmodified methyl ketones and o-aminoaromatic
aldehydes. Regioselectivity increased with slow addition of the methyl ketone
substrate to the reaction mixture.48
Introduction to 1,8-Naphthyridines
57
Y NH2 Y N
CHOR
1.1 eq. (TABO)
5 mol % H2SO4
Y = N, CH, CBr
RO
1.1 eqEtOH, 65oC, 150 min
HN
Y N
R
9 : 1 35
A novel copper-catalyzed [5+1] annulation of 2-ethynylanilines with
an N,O-acetal gives quinoline derivatives with an ester substituent on the 2-
position (36). A combination of CuBr2 and trifluoroacetic acid (TFA) promotes
a [5+1] annulation of 2-ethynylaniline with ethyl glyoxylate in the presence of
piperidine.49
Y NH2
1 eq. piperidine, 0.1 eq. CuBr2
Y = N, CH
H
4 eq. Na2SO4, 0.1 eq. TFA, EDC,Reflux, 1 h.Y N
OEtRR
O
O
OEt
O
36
Mogilaiah et al.50
have been reported an efficient and convenient method for
synthesis of 1-(5-aryl-[1,3,4]oxadiazol-2-ylmethyl)-3-(3-trifluromethyl-phenyl-
1H-[1,8]naphthyridin-2-ones (37), by the oxidation of [2-oxo-3-(3-
trifluoromethyl-phenyl)-2H-[1,8]naphthyridin-1-yl] acetic acid
arylildenehydrazides with iodobenzene diacetate under microwave irradiation in
solvent free condition.
N N O
O
NN
Ar
CF3
37
Ar = C6H5, 4-CH3C6H4
Introduction to 1,8-Naphthyridines
58
Mogilaiah et al.51
have been synthesized of 1,3,4-oxadiazolyl-1,8-
naphthyridines using iodobenzene diacetate in solid state. A simple and highly
efficient procedure has been described for the synthesis of 1-((5-phenyl-1,3,4-
oxadiazol-2-yl)methyl)-3-m-tolyl-1,8-naphthyridin-2(1H)-one (38) by the
oxidation of the corresponding [2-oxo-3-(3-methylphenyl)-2H-
[1,8]naphthyridin-1-yl]acetic acid arylidene hydrazides with iodobenzene
diacetate [ph(OAc)2] in solid state.
N N O
O
NN
C6H5
38
3. PHYSICOCHEMICAL PROPERTIES:
The physical properties and X-ray crystallographic analysis recorded
that all naphthyridines are planar with the exception of 1,8-naphthyridine is
non-planar due to repulsion of the nitrogen lone pairs of electrons, but becomes
planar when chelation with metal atom.52
The weaker bases of parent
naphthyridines than quinoline (pka 4.94) and isoquinoline (pka 5.40) are
attributed to the electron-withdrawing inductive effect of one doubly bonded
nitrogen atom to the other.53
In the fact that 1,6-naphthyridine (pka 3.78) and
1,7-naphthyridine (pka 3.63) are stronger bases as compared to the 1,5-
naphthyridine (pka 2.91) and 1,8-naphthyridine (pka 3.39) and also both of the
new derivatives are stronger bases as compared with the pka value of quinoline
and isoquinoline which they are consistent protonation occurring on N-6 and
Introduction to 1,8-Naphthyridines
59
N-7 of the 1,6- and 1,7-isomer respectively.54
A new series of fluorophore
derivatives from 1,8-naphthyridine were developed and shown the first
naphthyridine PET sensor that can signal Cd selectively with fluorescent
enhancement and red-shift. Other 1,8–naphthyridines were found to be
fluorescent in solution and they were studied in the presence of Cu+ and Cu
2+
ions and it was verified that the metal causes the quenching of their
fluorescence emission, due to the formation of complexes between the
naphthyridine and the metal.55, 56
Many 1,8-naphthyridine derivatives were characterized by single crystal
X-ray diffraction analysis, and a comprehensive study of their spectroscopic
properties involving experimental and theoretical studies. They found an
intramolecular 1,3-hydrogen transfer and photo-induced isomerization for some
derivatives while flexible structures was observed under 365 nm light
irradiation. Quantum chemical calculations revealed that the dinuclear
complexes with structural asymmetry exhibit different metal-to-ligand charge-
transfer transitions.57
4. REACTIVITY:
The naphthyridines possess ten delocalized π– electrons which are
located in five molecular orbitals and they are distorted by the presence of the
nitrogen atoms that causing an electron drift in that direction. This perturbation
causes the position ortho and para to the nitrogen atoms to have π–electron
densities than the meta-positions and this led to electrophilies react
preferentially at a position meta to a ring nitrogen and nucleophiles at ortho and
Introduction to 1,8-Naphthyridines
60
para-positions. However, because naphthyridines are π–electrons deficient,
they are highly susceptible to nucleophilic attack and strongly deactivated for
electrophilic attack.58
4.1. ELECTROPHILIC SUBSTITUTION:
In the bromination of 1,8-naphthyridine hydrobromide with 1:1
equivalent ratio of bromine in nitrobenzene, the 3-bromo-1,8-naphthyridine
(39) and 3,6- dibromo-1,8-naphthyridine (40) were obtained in equivalent ratio
(1:1), but compound (40) is obtained in 73% yield when equivalent ratio of
bromine is ((2:5). 59
N N
H Br
Br2
Nitrobenzene N N N N
Br Br Br
39 40
However, presence of electron-donating substituents facilitates
electrophilic substitution and hence bromination was proceed under much
milder conditions as shown in conversion of naphthyridin-2-one derivatives
(41) into 3-bromo-naphthyridin-2-one derivatives (42).60
N NH
Br2 in AcOH
N NH
Br
41 42
O KBrO3 in HBr O
Oxidation reaction61
with KClO3 in HCl and the nitration occurs only
when electron-donating groups are present in the 2-or 4-position. Thus,
Introduction to 1,8-Naphthyridines
61
1,7-naphthyridone (11) can be mononitrated to 3-nitro-1,7-naphthyridone
(12).63
NNH
NNH
43 44
Fumming HNO3
O O
NO2
4.2: NUCLEOPHILIC SUBSTITUTION
Naphthyridines are very easily undergoing nucleophilic substitution
reactions because of the presence of nitrogen atoms in their ring system thus
they easily undergo nucleophilic attack. There are numerous investigations
using nitrogen nucleophilies.64, 65
The replacement of halogen by an amino
group provides potential application in synthetic chemistry and is therefore a
topic of great interest. It is apparent that nucleophilic substitution of halo
pyridine can proceed in three pathways namely ipso, cine and tele substitutions
Figure-1.66
N
N
N
N
N
N
Nu
NuNu
Nu
Nu
X
tele cine
ipso
Figure1: Ipso, cine and tele nucleohilic substitution of naphthyridines
The mechanism for the formation of both cine and ipso products can be
Introduction to 1,8-Naphthyridines
62
explained via a didehydronaphthyridine intermediate (45), so, the reactions of
4- bromonaphthyridine (46) and 3-bromonaphthyridine (47) with potassium
amide in liquid ammonia afford 4- aminonaphthyridine (48) and 3-
aminonaphthyridine (49) figure-2.67
N
N
N
N
N
NH2
Figure-2: Mechanism of formation of ipso and cine products
N
N
Br
Br
N
NH2
45
47
4648
49
Aminodehalogenations involving tele and ipso substitution have been
reviewed. The replacement of a halogen by a hydrogen atom is conveniently
achieved by initial reaction with hydrazine followed by oxidation with copper
(II) sulphate.68
4.3. REDUCTION:
The hydrogenation over PtO2 or Pd gives preferentially tetrahydro
products.69
But sodium and alcohol afford the fully reduced trans isomers only.
However, both cis and trans isomers were obtained when reduction is done
over PtO2 in acetic acid. The hydrogenation of naphthyridines has been
reviewed.70
Lithium aluminum hydride changes the 8-oxo-1,7-naphthyridine
(50) and the 4,6-dioxo-1,5-naphthyridine (51) into tetrahydro-1,7-
naphthyridine (52) and tetrahydro-1,5- naphthyridine (53) respectively
Scheme-4. 71, 72
Introduction to 1,8-Naphthyridines
63
NN
NN
HN
N
HN
N
R
OR
LiAlH4
LiAlH4
O
O
50
51
52
53
4.4. ADDITION REACTION:
The Reissert reaction of naphthyridine with acyl halides and potassium
cyanide has been studied including conversion of 1,7-naphthyridine into 7-
acyl-8-cyano- 1,7-naphthyridine (54).73
NN
NN
RCOCl
54
KCNH
CNR
O
In the addition reaction of 1,6-naphthyridine with acetic anhydride, 6-
acetyl-1,6-naphthyridine-5-acetic acid (55) was obtained, while the reaction of
1,6-naphthyridine with diethylmalonate and acetic anhydride gave 6-acetyl-5-
diethyl malonate-1,6-naphthyridine (56).74, 75
N
N
56 55
Ac2O
N
N
2
CH2(CO2Et)2 Ac2O
CH(CO2Et)2
O N
N
CH2CO2H
O
N-alkylation preferentially takes place on the isoquinoline nitrogen as
shown in the reaction of 1, 6-naphthyridine to give 6-methyl-1, 6-
naphthyridone (57).76
Introduction to 1,8-Naphthyridines
64
57
N
N
i) CH3IN
N
O
ii) [O]
In view of the hitherto importance of 1,8-naphthyridines with various
structural features exhibiting a range of biologically useful properties, the
present investigation involves the synthesis of 1,8-naphthyridine derivatives
and are presented in the forth coming chapters.
Introduction to 1,8-Naphthyridines
65
REFERENCES
1. Reissert, A., Berichte, 1893, (26), 2137.
2. Bobranski, B., Sucharda, E. Berichte, 1927, (60), 1081
3. Koller, G., Berichte, 1927, (60), 1918.
4. Ikekawa, N., Chem. Pharm. Bull. 1958, (6), 263, 269, 401.
5. a) Giacomello, G., Gualteri, F., Ricceri, F. M., Stein, M. L. Tetrahedron
Lett., 1965, 1117. b) Tan, R., Taurins, A., Tetrahedron Lett. 1965, 2737.
6. Bouzard, D., DiCesare, P., Essiz ,M., Jacquet, J. P., Ledoussal, B.,
Remuzon, P., Kessler, R. E., Fung Tomc, J., J. Med. Chem., 1992, 35,
518.
7. Rao, G. R., Mogilaiah, K., Sreenivasulu, B., Indian J. Chem., 1996, 35B,
339.
8. Laxminarayana, E., Karunakar, T., Shankar, S. S., Chary, M. T.,
Advanced Drug Delivery Reviews, 2012, 2, 6.
9. a) Ferrarini, P. L., Manera, C., Mori C., Badawneh, M., Saccomanni, G.,
Farmaco., 1998, 53, 741. b) Aboul-Fadl, T., Bin-Jubair, F. A. S., Aboul-
Wafa, O., Eur. J. f Med. Chem., 2010, 45, 4578.
10. Zhang, S. X., Bastow, K. F., Tachibana, Y., Kuo, S. C., Hamel, E.,
Mauger, A., Narayanan, V. L., Lee K. H., J. Med. Chem., 1999, 42,
4081.
11. a) Kuroda, T., Suzuki, F., Tamura, T., Ohmori, K., Hosoe, H., J. Med.
Chem., 1992, 35, 1130. b) Roma, G., Grossi, G., Eur. J. Med. Chem.
2008, 43 (8), 16658.
Introduction to 1,8-Naphthyridines
66
12. Ferrarini, P. L., Mori, C., Badawneh, M., Farmaco, 2000, 55, 603.
13. Ferrarini, P. L., Badawneh, M., Franconi, F., Manera, C., Miceli, M.,
Mori, C., Saccomanni, G., Farmaco., 2001, 56, 311.
14. Santilli, A., Scotese, A. C., Bauer, R. F.; Bell, S. C. J. Med. Chem., 1987,
30, 2270.
15. Kuo, S.-C., Tsai, S.-Y., Li, H.-T., Wu, C.-H., Ishii, K., Nakamura, H.,
Chem. Pharm. Bull., 1988, 36, 4403.
16. Ferrarini, P. L., Mori, C., Tellini, N., Farmaco., 1990, 45, 385.
17. Massari, V., Daelemans, D., Barreca M. L. , J. Med. Chem. 2010, 53,
641.
18. Fadda, A. A., El-Defrawy, A. M., El-Habiby, S. A., The American
Journal of Organic Chemistry, 2012, 2 (4), 87.
19. DaSettimo, A., Primofiore, G., DaSettimo, F., Simorini, F., Barili, P. L.,
Senatore, G., Martini, C., Lucacchini, A., Drug Des. Discov., 1994, 11,
307.
20. Gilis, P. M., Haemers, A., Bollaert, W., J. Heterocycl. Chem., 1980, 17,
717.
21. Marchese, A., Debbia, E. A., Schito, G. C., J. Antimicrobial
Chemotherapy, 2000, 46, 11.
22. Tun-Chieh Chen, Ya-Ling Hsu, Yu-Chieh Tsai, Yu-Wei Chang, Po-Lin
Kuo, Yen-Hsu Chen., J. Mol.Med., 2014, 92(1), 53.
23. Ferrarini, P. L., Mori, C., Tellini. N., Farm. Ed. Sci., 1990, 45, 385.
24. Lirvinov, V. P., Adv. Heterocycl. Chem., 2006, 91, 222.
Introduction to 1,8-Naphthyridines
67
25. Helmut, H., Juergen, P., Hans, Z., Bruno, W., Otto, K. W., Ger. Offen,
3907938, 1990, Chem. Abstr., 114, 122342f , 1991.
26. Muller, C. J., Grahner, B., Heber, D., Pharmazie., 1994, 49, 878.
27. Badawneh, M., Ferrarini, P. L., Calderone, V., Manera, C., Martinotti,
E., Mori, C., Saccomanni, G., Testai, L., Eur. J. Med. Chem., 2001, 36,
925.
28. Ferrarini, P. L., Manera, C., Mori, C., Badawneh, M., Saccomanni, G.,
Farmaco., 1998, 53, 741.
29. Chen, K., Kuo, S. C., Hsieh, M. C., Mauger, A., Lin, C. M., Hamel, E.,
Lee, K. H., J. Med. Chem., 1997, 40, 2266.
30. Chen, K., Kuo, S. C., Hsieh, M. C., Mauger, A., Lin, C. M., Hamel, E.,
Lee, K. H., J. Med. Chem., 1997, 40, 3049.
31. Mohamed, E. A., Abdel-Rahman, R. M., El-Gendy, Z., Ismail, M. M., J.
Serb. Chem. Soc., 1993, 58, 1003.
32. Mohamed, E. A., Abdel-Rahman, R. M., El-Gendy, Z., Ismail, M. M,. J.
Indian Chem. Soc., 1994, 71, 765.
33. Seada, M., El-Behairy, M. A., Jahine, H., Hanafy, F., Orient. J. Chem.,
1989, 5, 273.
34. Nyce, P. L., Steinman, M., Synthesis, 1991, 571.
35. Ferrarini, P. L., Mori, C., Primofiore, G., Gazlolari, L., J. Heterocycl.
Chem., 1990, 27, 881.
36. Abbiati, G., Arcadi, A., Martinelli, F., Rossi, E., Synthesis, 2002, 1912.
Introduction to 1,8-Naphthyridines
68
37. Sakamoto, T., Kondo, Y., Yamanaka, H., Chem. Pharm. Bull., 1985, 33,
4764.
38. Hartner, F. W., Hsiao, Y., Eng, K. K., Rivera, N. I., Paluki, M., Tan, L.,
Yasuda, N., Hughes, D. L., Weissman, S., Zewge, D., King, T., Tschaen,
D., Volante, R. P., J. Org. Chem., 2004, 69, 8723.
39. Bernstein, J., Stearns, B., Shaw, E., Lott, W. A., J. Am. Chem. Soc.,
1947, 69, 1151.
40. Mogilaiah, K., Rao, R. B., Synth. Commun., 2003, 32, 747.
41. Mazza F. P. and C. Migliardi, Atti Accad. Sci. Torino, Classe Sci. fis.,
Mat. Nat., 1940, 75, 438; Chem. Abstr., 1942, 36, 5477.
42. Mogilaiah, K., Reddy, G. R., J. Chem. Res., 2004, 145
43. Baldwin, J. J., Engelhardt, E. L., Hirschmann, R., Ponticello, G. S.,
Atkinson, J. G., Wasson, B. K., Sweet, C. S., Scriabine, A., J. Med.
Chem., 1980, 23, 65. B) Mogilaiah, K., Reddy, G. R., J. Chem. Res.,
2004, 145.
44. Dormer, P. G., Eng, K. K., Farr, R. N., Humphrey, G. H., McWilliams,
J.C., Reider, P.J., Sager, J. W., Volante, R. P., J. Org. Chem., 2003, 68,
467.
45. Sakai, N., Tamura, K., Shimamura, K., Ikeda, R., Konakahara, T., Org.
Lett., 2012, 14, 836.
46. Newcome, G. H., Garbis, S. J., Majestic, V. K., Fronczek, F. R. & Chiari,
G., J. Org. Chem. 1981, 46, 833.
Introduction to 1,8-Naphthyridines
69
47. Eichler, E., Rooney, C. S., Williams, H. W. R., J. Heterocycl. Chem.,
1976, 13, 841.
48. Muchowski, J. M., Maddox, M. L., Can. J. Chem. 2004, 82, 461.
49. Nyce, P. L., Steinman, M. Synthesis, 1991, 571.
50. Mogilaiah, K., Shiva Kumar, K., Kumar Swamy, J. Ind. J. Chem., 2010,
49B, 840.
51. Mogilaiah, K., Sharath Babu, H, Shiva Prasad, R. Ind. J. Chem., 2009, 48B,
868.
52. Hawes, E. M., Wibberley, D. G., J. Chem. Soc. (C). 1966, 315.
53. Albert, A., J. Chem. Soc. 1960, 1790.
54. Paudler, W. W., and Kress, T. J., J. Heterocycl. Chem. 1968, 5, 561.
55. Ying Zhou, Yi Xiao, and Xuhong Qian. Tetrahedron Letters. 2008, 49,
3380.
56. Nicoleti, C. R., Garcia, D. N., da Silva, L. E., Begninim, I. M., Rebelo,
R. A., Joussef, A. C., Machado, V. G., J. Fluoresc. 2012, 22, 1033.
57. Fu W. F., Jia, L. F., Mu, W. H., Gan, X., Zhang, J. B., Liu, P. H., Cao, Q.
Y., Zhang, G. J., Quan, L., Lv, X. J., Xu, Q, Inorg. Chem. 2010, 49(10),
4524.
58. Katritzky, A. R., Rees, C. W., Pergamon Press, Oxord, 1984, 2, 581.
59. Kress, T. J., Costantino, S. M., J. Heterocycl. Chem. 1973, 10 (3), 409.
60. Wozniak, M., Van der Plass, H. C., J. Heterocycl. Chem. 1978, 15, 731.
61. Brown, E. V., Mitchell, S. R., J. Org. Chem. 1975, 40, 660.
62. Alder, T. K., Albert, A., J. Chem. Soc. 1960, 1794.
Introduction to 1,8-Naphthyridines
70
63. Pomorski, J., Den Hertog, H. J., Rocz. Chem., 1973, 47, 549.
64. Van der Plas, H. C., Wozniak, M., Van den Haak, H. J. W., Adv.
Heterocycl. Chem. 1983, 33, 95.
65. Wozniak, M., Van der Plass, H. C., J. Heterocycl. Chem. 1986, 23, 473.
66. Den Hertog, H. J., Van der Plas, H. C., Adv. Heterocycl. Chem. 1965, 4,
121.
67. Ferrarini, P. L, Mori, C. and Van der Plass, H. C., J. Heterocycl. Chem.
1986, 23, 501.
68. Ferrarini, P. L. Mori, C. Primofiore, G. Da Settimo, A.. Breschi, M. C.,
Martinotti, E., Nieri, P., Ciucci, M. A., Bur., J. Med. Chem. 1990, 25
(26), 489.
69. Armarego, W. L. F., J. Chem. Soc, (C). 1967, 5, 377.
70. Paudler, W. W., Kress, T. J., Adv. Heterocycl. Chem. 1970, 11, 123.
71. Sato, Y., Iwashige, T., Miyadera, T., Chem. Pharm. Bull. 1960, 8, 427.
72. Alhaique, F., Riccieri, F. M., Campanella, L., Ann. Chim. (Rome). 1972,
62, 239.
73. Takeuchi, I., Hamada, Y., Chem. Pharm. Bull. 1976, 24, 1813.
74. Yamanaka, H., Shiraishi, T., Sakamoto, T., Chem. Pharm. Bull. 1981, 29,
1056.
75. Yamazaki, T., Takahata, H., Matsuura, T., Castle, R. N., J. Heterocycl.
Chem. 1979, 16, 527.
76. Bunting, J. W., J. Chem. Soc., Perkin Trans., 1974, 1, 1833.