Synthesis of biologically important phthalazinones, 2,3-benzoxazin-1-ones and isoindolinones from ninhydrin and their antimicrobial activity

Article abstract of DOI:10.1016/j.tetlet.2013.04.015

Biologically important phthalazinones, 2,3-benzoxazin-1-ones and isoindolinones have been synthesized from easily available ninhydrin in good yields. The appropriate ninhydrin adducts 2,2,-diaryl-1,3-indanediones and 3-(diarylmethylene)isobenzofuranones w

Full text of DOI:10.1016/j.tetlet.2013.04.015

Tetrahedron Letters 54 (2013) 3137–3143
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of biologically important phthalazinones, 2,3-benzoxazin-1-ones
and isoindolinones from ninhydrin and their antimicrobial activity
Sudipta Pathak a, Kamalesh Debnath a, Sk Tofajjen Hossain b, Samir Kumar Mukherjee b,
Animesh Pramanik a,
⇑
a Department of Chemistry, University of Calcutta, 92, A.P.C. Road, Kolkata 700 009, India
b Department of Microbiology, University of Kalyani, Kalyani 741 235, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Biologically important phthalazinones, 2,3-benzoxazin-1-ones and isoindolinones have been synthesized
from easily available ninhydrin in good yields. The appropriate ninhydrin adducts 2,2,-diaryl-1,3-indan-
ediones and 3-(diarylmethylene)isobenzofuranones were treated with various nucleophiles like hydra-
zine hydrate, hydroxylamine, and phenylhydrazin to accomplish the heterocycles. The synthesized
compounds were assayed for their antibacterial activity and showed significant activity against both
the selected Gram positive and Gram negative bacteria, suggesting possible scope of using as
antimicrobials.
Received 23 January 2013
Revised 1 April 2013
Accepted 3 April 2013
Available online 11 April 2013
Keywords:
Phthalazinones
2,3-Benzoxazin-1-ones
Isoindolinones
Ninhydrin
Ó 2013 Elsevier Ltd. All rights reserved.
Microwave irradiation
Antimicrobials
Phthalazinones are an important class of heterocycles with di-
verse biological activities like Vasorelaxant activity,1 phosphodies-
terase inhibitors,2 inhibitor of Poly(ADP-ribose),3 antiplatelet,4
Aurora-A kinase inhibitors (structure A, Fig. 1),5 or anti-allergic rhi-
nitis activity (structure B, Fig. 1).6 Benzoxazinones are found in
nature as phytoalexins avenalumin I7 and dianthalexin.8 Some
derivatives of 3,1-benzoxazinones act as human immunodeficiency
virus type 1 (HIV-1) specific non-nucleoside reverse transcriptase
inhibitor (NNRTI),9 competitive inhibitors,10 neutrophil elastase
inhibitors,11, and others.12 The tetrahydronaphthalene-benzox-
azine glucocorticoid receptor (GR) partial agonist C (Fig. 1) is opti-
mized to produce potent full agonists of GR.13 Another class of
heterocycles with isoindolinone core are also found in natural
products such as vitedoamine A, chilenine, lennoxamine, magal-
lanesine, and nuevamine and all of them have gained considerable
synthetic attention.14 N-analogous corollosporines with isoindoli-
nones moiety D (Fig. 1) revealed antibiotic activity, which is com-
parable to the natural product corollosporine.15 Therefore, and
within the realm of medicinal chemistry, phthalazinone, benzoxaz-
inone, and isoindole derivatives are expected to be important syn-
thetic targets in organic chemistry for their immense biological
activities.16
Spread of infectious diseases caused by bacteria has increased
in recent years. In spite of many significant advances in antibacte-
rial therapy, the extensive use and misuse of antibiotics have
caused the emergence of bacterial resistance to antibiotics, which
causes a serious threat to public health. In particular, the emer-
gence of multi drug resistant gram-positive bacteria, including
methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-
resistant S. aureus (VRSA), and vancomycin-resistant Enterococci
(VRE), has become a serious problem in the treatment of bacterial
diseases.17 Therefore, the synthesis of new compounds to deal with
resistant bacteria has become one of the most important areas of
antibacterial research today.15,18 In continuation of our research
interest in the synthesis of various heterocyclic compounds from
ninhydrin,19 we wish to report herein some general and efficient
methods for the synthesis of a series of 4-[(20-hydroxyaryl)-(50-hy-
droxy-30-methyl-1H-pyrazol-40-yl)-methyl]-2H-phthalazin-1-ones
(1), 4-[bis-(aryl)-methyl]-benzo[d]-[1,2]oxazin-1-ones, (2) and
3-[bis-(aryl)-methyl]-3-hydroxy-2-phenylamino-2,3-dihydro-isoin-
dol-1-ones (3) from easily available ninhydrin and evaluation of
their antimicrobial activity.
We attempted to synthesize phthalazinones (1) which are
structurally similar to phthalazinones of general structure A
(Fig. 1)7 from easily available ninhydrin. Since the C-2 position of
ninhydrin is active to nucleophilic attack,19–21 initially a mixture
of ninhydrin and the nucleophilic heterocycle 5-methyl-2H-pyra-
zole-3-ol was stirred in acetic acid for 10 min at room temperature.
⇑
Corresponding author. Tel.: +91 33 2484 1647; fax: +91 33 2351 9755.
E-mail address: animesh_in2001@yahoo.co.in (A. Pramanik).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.04.015

3138
S. Pathak et al. / Tetrahedron Letters 54 (2013) 3137–3143
Cl
R2
H
N
N
F3C
OH
NH2
O
H
N
N
O
N
O
N
N
N
N
N
O
n
O H
5
R1
O
O
N
D
A
C
B
Figure 1. Biologically important phthalazinones (A, B), benzoxazinone (C), and isoindolinone (D).
4
R
3
R
OH
O
O
2
R
1
R
4
R
3
R
OH
N
N
OH
N
H
2
NH
R
O
5
O
1
HO
R
OH
OH
OH
N
NH
i
ii
iii
O
4
R
N
O
OH
N
O
H
3
OH
R
O
1
4
2
R
1
3
4
2
a: R = R = R = H, R = CH3
1
R
1
3
4
2
O
b: R = R = R = H, R = Cl
1
4
2
3
c: R = R = H, R = Cl, R = CH3
N
3
4
1
2
OH
d: R = R = H, R ,R = -C4H4-
N
H
1
1
3
3
4
4
2
2
e: R = R = R = H, R = F
6
f: R = R = R = H, R = OCH3
1
3
2
4
g: R = R = H, R = R = Cl
Scheme 1. Reagents and conditions: (i) 5-methyl-2H-pyrazole-3-ol, acetic acid, 10 min, rt; (ii) substituted phenols, acetic acid, cat. H2SO4, reflux; (iii) hydrazine hydrate, rt.
1-ones 1 were formed in high yields (Scheme 1, Table 1, and
Table 1
Fig. 2).22,23 The ninhydrin adducts 4 and 6 which were isolated dur-
Synthesis of phthalazinones 1a–g from adducts 6a–g
ing the course of the synthesis are also potentially bioactive com-
Adduct
Product
Time (h)
Yielda (%)
Melting point (°C)
pounds since structurally similar compounds have been reported
to possess biological activity.20
6a
6b
6c
6d
6e
6f
1a
1b
1c
1d
1e
1f
26
24
23
30
22
29
24
92
89
90
80
88
80
78
301–303
260–262
254–256
196–198
236–238
230–232
222–224
The formation of phthalazinones 1 from adducts 6 can be ex-
plained on the basis of the proposed mechanism depicted in
Scheme 2 which is in accordance with the previously proposed
mechanism.19c–e In basic condition, the breaking of the central C–
C bond of the bicycle[3.3.0]octano systems 6 affords eight-mem-
bered lactam intermediate 7 which subsequently tautomerizes to
keto form 8. Then the ketonic carbonyl preferentially condenses
with hydrazine to furnish intermediate 9. Finally the intramolecu-
lar nuclephilic attack of amino group to lactone carbonyl produces
the products 1.
To synthesize heterocycles 2,3-benzoxazin-1-ones (2) and iso-
indolinones (3) the appropriate ninhydrin adducts 2,2-diaryl-1,3-
indanediones 10 were initially derived from ninhydrin by acid
catalyzed condensation with arenes (Scheme 3).21 Subsequently
the adducts 10 were converted to 3-(diarylmethylene)isobenzof-
uranones 11 through base catalyzed rearrangement.19j Although
10 and 11 are isomeric compounds, due to the presence of five-
membered lactone ring and exocyclic methylene group, the inter-
mediates 11 were expected to be more reactive than intermediates
6g
1g
a
Isolated yields.
The acid catalyzed condensation produced the adduct 2-hydroxy-
2-(50-hydroxy-30-methyl-1H-pyrazol-40-yl)-indane-1,3-dione 4 in
very good yield (Scheme 1). Subsequently the adduct 4 was re-
fluxed with para substituted phenols in acetic acid with a catalytic
amount of H2SO4 for 1 h. This second condensation produced the
adducts 2,2-diaryl-1,3-indanediones 5 in very good yields; adducts
so formed preferentially remained in the cyclic hemiketal form 6
which was confirmed by X-ray diffraction study (Supplementary
data). Finally when the adducts 6 were stirred in hydrazine hydrate
at room temperature for 22–30 h the products 4-[(20-hydroxyaryl)-
(50-hydroxy-30-methyl-1H-pyrazol-40-yl)-methyl]-2H-phthalazin-

S. Pathak et al. / Tetrahedron Letters 54 (2013) 3137–3143
3139
Figure 2. ORTEP diagram of X-ray crystal structure of compound 1g with atom numbering scheme. Thermal ellipsoids are shown at the 50% probability (CCDC number
917563).
O
O
HO
R
Het
R
Het
O
R
Het
O
O
O
H
O
6
O
NH2
7
8
H2N
H2N NH2
H
N
NH2
OH
N
N
Het
=
R
R
Het
OH
Het
N
NH
O
O
O
9
1
Scheme 2. Reaction mechanism for the formation of phthalazinones 1.
10 toward various nucleophiles. As predicted, the intermediates 11
were found to condense with hydroxylamine hydrochloride under
refluxing condition to produce 2,3-benzoxazin-1-ones 2 in moder-
ate yields (Scheme 3 and Table 2),22 whereas the intermediates 10
were found to remain unreactive under similar reaction condition.
The formation of products 2 was confirmed by NMR and X-ray
crystal structure analysis (Fig. 3).23 Under conventional heating
the above reactions took longer times (about 13–18 h) and the
yields were moderate (Table 2). But under microwave heating
the reaction times were reduced drastically to 40–60 min and also
the yields of the reactions were enhanced considerably compared
to conventional heating (Table 2). Intermediates 10 failed to react
with hydroxylamine hydrochloride both under conventional and
microwave heating.
A proposed mechanism for the reaction of 11 with hydroxyl-
amine hydrochloride is depicted in Scheme 4. In basic medium
the nuclephilic attack of hydroxylamine to the lactone carbonyl
of 11 produces an open chain intermediate 13, which tautomerizes
to intermediate 14. The intermediates 14 remain in equilibrium
with five-membered isoindolinone derivatives 12. In fact several
intermediates 12 (12c, 12d, and 12i) were isolated as major prod-
ucts when the reactions were carried out in a short time that is, 1 h
under conventional heating (Scheme 3 and Table 3). The nuclephil-
ic attack of another hydroxylamine to the carbonyl carbon of 14
furnishes the intermediate 15, which subsequently undergoes
intramolecular cyclization to generate the products 2.
When the five-membered lactones 11a–d were refluxed with
phenylhydrazine hydrochloride in the presence of sodium acetate,

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S. Pathak et al. / Tetrahedron Letters 54 (2013) 3137–3143
iii
Ar
Ar
Ar
Ar
Ar
O
HO
Ar
Ar
Ar
ii
i
N
O
O
N
OH
O
O
O
12
O
2
10
11
iv
Ar
f: Ar = p-OCH3-C6H4
g: Ar = 3,4-di-Cl-C6H3
h: Ar = p-Cl-m-CH3-C6H3
i: Ar = p-I-C6H4
a: Ar = Ph
b: Ar = p-F-C6H4
c: Ar = p-Cl-C6H4
d: Ar = p-Br-C6H4
e: Ar = p-CH3-C6H4
HO
Ar
H
N
N
Ph
O
3
Scheme 3. Reagents and conditions: (i) hydroxylamine hydrochloride, NaOAc, EtOH, H2O, conventional reflux, 1 h; (ii) hydroxylamine hydrochloride, NaOAc, EtOH, H2O,
conventional reflux, 13–18 h; (iii) hydroxylamine hydrochloride, NaOAc, EtOH, H2O, conventional reflux, or microwave irradiation; (iv) phenylhydrazine hydrochloride,
NaOAc, EtOH, H2O, conventional reflux, 6–10 h.
isoindolinones 3a–d were formed in very good yields (Scheme 3,
Table 3).22 The product formation was confirmed by NMR and X-
ray diffraction studies (Fig. 4).23 The mechanism of formation of
the products 3 follows the same as that of hydroxylamine in the
formation of 12 (Scheme 4).In this case the second nucleophilic at-
tack did not take place because of the greater steric bulkiness of
phenylhydrazine. Both 12 and 3 are isoindolinone derivatives
and expected to show biological activity.
Primary bioassay screening gave the preliminary indication of
bioactivity of the compounds and helped to identify lead com-
pounds for a more detailed pharmacological evaluation. The syn-
thesized compounds 1a, 2a, and 3a were screened against two
Gram negative (Escherichia coli and Klebsiella pneumoniae) and
Table 2
Synthesis of 2a–h from 11a–h by conventional and microwave heating
Product
Conventional heating
Microwave heating
Melting
point (°C)
Time (h)
Yielda (%)
Time (min)
Yielda (%)
2a
2b
2c
2d
2e
2f
18
13
16
17
18
20
15
16
54
57
61
56
52
41
52
55
60
35
45
45
50
60
40
50
60
67
72
64
60
50
62
66
150–152
158–160
195–197
222–224
176–178
148–150
218–220
198–200
2g
2h
a
Isolated yields.
Figure 3. ORTEP diagram of X-ray crystal structure of compound 2c with atom numbering scheme. Thermal ellipsoids are shown at the 50% probability (CCDC number
885624).

S. Pathak et al. / Tetrahedron Letters 54 (2013) 3137–3143
3141
Ar
Ar
N
OH
NHOH
Ar
Ar
Ar
Ar
O
Ar
Ar
Ar
Ar
:NH2OH
:NH2OH
-
NH2OH
OH
N
O
O
H
H
- H2O
N
N
OH
OH
O
O
O
2
O
O
14
15
11
13
Ar
HO
Ar
N
OH
O
12
Scheme 4. Reaction mechanism for the formation of 2,3-benzoxazin-1-ones 2.
two Gram positive (Staphylococcus aureus and Bacillus subtilis) bac-
teria.24 The minimum inhibitory concentration (MIC) values are gi-
ven in Table 4. The percent survival values of the test bacterial
strains against the compounds at different concentration are pre-
sented in Figure 5. From these observations, it could be revealed
that all the three compounds 1a, 2a, and 3a have significant anti-
bacterial activity against both Gram positive and Gram negative
bacteria (Table 4). MIC values are slightly higher than the conven-
tional antibacterial agents depending on the susceptibility.25 There
is a huge variation in the time for emergence of drug resistance
which varies among organisms and drugs.26 Resistance rises to
Table 3
Synthesis of isoindolinones 3a–d and 12c,d,i from intermediates 11
Product
Time (h)
Yielda (%)
Melting point (°C)
3a
3b
3c
3d
12c
12d
12i
10
6
8
9
1
85
86
87
83
66
58
62
210–212
215–217
133–135
145–147
205–207
135–137
148–150
1
1
a
Isolated yields.
C20
C19
C21
C16
C3
C2
C15
C27
C18
01
C1
N1
C17
C4
C22
C14
C5
C6
C26
N2
C7
C23
C13
C12
C25
C24
C8
C11
O2
C9
C10
Figure 4. ORTEP diagram of X-ray crystal structure of compound 3a with atom numbering scheme. Thermal ellipsoids are shown at the 50% probability (CCDC number
885625).

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S. Pathak et al. / Tetrahedron Letters 54 (2013) 3137–3143
Table 4
MIC values of the compounds 1a, 2a, and 3a against two representatives of both Gram positive and Gram negative bacteria
Compound used
B. subtilis (lg/mL)
S. aureus (lg/mL)
E. coli (
lg/mL)
K. pneumoniae (lg/mL)
1a
2a
3a
93
185
109
115
170
97
108
133
78
127
115
95
Figure 5. The percent survival values of the test bacterial strains against the synthesized compounds 1a, 2a, and 3a at different concentration (0–200 lg/mL): (a) Escherichia
coli; (b) Klebsiella pneumonia; (c) Bacillus subtilis; (d) Staphylococcus aureus. Percent survival of the test bacterial strains at different concentration regimes was determined by
viable cell count method after 24 h of exposure.
such a high level that it reduces the efficacy of the drugs against
bacteria. At this point, new antimicrobial formulations are re-
quired, which would be effective against resistant bacteria.27 The
results are thus meaningful in suggesting the scope of using these
compounds as possible antimicrobials. However, this requires fur-
ther research to elucidate the probable mechanism of action for
determining its selective toxicity and to find its efficacy against
multi-drug resistant pathogenic strains.
In conclusion, we have developed some simple and efficient
methodologies for the synthesis of diverse range of potentially bio-
active phthalazinones, 2,3-benzoxazin-1-ones and isoindolinones
from ninhydrin without using any metals or expensive reagents.
The significant advantages of these methodologies are cost effec-
tiveness, operational simplicity, good to excellent yields of the
products, and easy availability of starting materials. Therefore all
these may be very attractive methods of synthesis in chemical
and pharmaceutical industries. Some of the representative com-
pounds show significant antibacterial activity against both the se-
lected Gram positive and Gram negative bacteria, suggesting
possible scope of using as antimicrobials. Moreover the synthe-
sized compounds may also show other types of biological activities
as mentioned in the introduction of the Letter. The X-ray crystal
structures of various compounds and intermediates reported in
this Letter may help to explore the structure–function relationship
in biological evaluation.
(JRF) respectively. The financial assistance of CSIR, New Delhi is
gratefully acknowledged [Major Research Project, No. 02(0007)/
11/EMR-II]. Crystallography was performed at the DST-FIST, In-
dia-funded Single Crystal Diffractometer Facility at the Depart-
ment of Chemistry, University of Calcutta.
Supplementary data
Supplementary data (IR, 1H, 13C data of compounds 1b–g, 2b–h,
12c, 12d, 12i and 3b–d and crystallographic data for 4, 6b, 12i)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2013.04.015.
References and notes
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22. (a) General procedure for the synthesis of compounds 1a–g: The appropriate
substrate 6a–g (1.4 mmol) was added to hydrazine hydrate (10 ml, 90%) in a
100 ml round bottomed flask and the reaction mixture was stirred at room
temperature for 23–30 h (as mentioned in Table 1). The solid product
precipitated out from the reaction mixture was filtered and washed
thoroughly with water; (b) General procedure for the synthesis of compounds
2a–h: The appropriate substrate 11a–h (1.4 mmol) was added to a mixed
solution of ethanol (15 ml) and water (7 ml) followed by the addition of
hydroxylamine hydrochloride (650 mg, 9.4 mmol) and sodium acetate
(770 mg, 9.4 mmol). The reaction mixture was refluxed either by
conventional heating or microwave irradiation (as mentioned in Table 2).
Then from the cold reaction mixture white crystalline solid products 2 were
precipitated out on slow evaporation of ethanol; (c) General procedure for the
synthesis of compounds 3a–d and 12c,d,i: The appropriate substrate 11
(1.4 mmol) was added to a mixed solution of ethanol (15 ml) and water
(7 ml) followed by the addition of appropriate nucleophile, phenylhydrazine
hydrochloride/hydroxylamine hydrochloride (9.4 mmol), and sodium acetate
(770 mg, 9.4 mmol). The reaction mixture was refluxed for the time mentioned
in Table 3. Then from the cold reaction mixture white crystalline products 3
and 12 were precipitated out on slow evaporation of ethanol.
14. (a) Taniguchi, T.; Iwasaki, K.; Uchiyama, M.; Tamura, O.; Ishibashi, H. Org. Lett.
2005, 7, 4389; (b) Kim, G.; Jung, P.; Tuan, L. A. Tetrahedron Lett. 2008, 49, 2391.
15. Neumann, H.; Strübing, D.; Lalk, M.; Klaus, S.; Hübner, S.; Spannenberg, A.;
Lindequist, U.; Beller, M. Org. Biomol. Chem. 2006, 4, 1365.
23. 4-[(20-Hydroxy-50-methyl-phenyl)-(50-hydroxy-30-methyl-1H-pyrazol-40-yl)-
methyl]-2H-phthalazin-1-one (1a): White solid (466 mg, 92%), mp 301–303 °C;
IR (KBr): (cmꢀ1) 3192, 1649; 1H NMR (300 MHz, DMSO-d6) d: 12.3 (br s, 1H),
9.07 (br s, 1H), 8.21 (d, J = 7.8 Hz, 1H), 7.74–7.83 (m, 3H), 6.78 (d, J = 7.5 Hz,
1H), 6.61–6.66 (m, 2H), 5.87 (s, 1H), 2.04 (s, 3H), 1.77 (s, 3H); 13C NMR
(75 MHz, DMSO-d6) d: 159.3, 152.1, 147.3, 138.1, 133.3, 131.0, 130.0, 129.6,
127.9, 127.8, 127.5, 127.4, 126.6, 126.0, 124.8, 114.6, 99.8, 35.4, 20.5, 10.9;
Anal. Calcd for C20H18N4O3: C, 66.29; H, 5.01; N, 15.46. Found C, 66.20; H, 4.94;
N, 15.38. 4-Benzhydryl-benzo[d][1,2]oxazin-1-one (2a): White solid (263 mg,
60%), mp 150–152 °C; IR (KBr): (cmꢀ1) 1737; 1H NMR (300 MHz, DMSO-d6) d:
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(h) Bhunia, A.; Yetra, S. R.; Biju, A. T. Chem. Soc. Rev. 2012, 41, 3140.
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Hu, Y.; Niu, Y.; Bai, G.; Wu, H.; Costanza, F.; West, L.; Harrington, L.; Shaw, L. N.;
Cao, C.; Cai, J. Chem. Commun. 2011, 47, 9729.
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Vakulenko, S.; Franzblau, S.; Möllmann, U. Org. Biomol. Chem. 2006, 4, 4178.
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Pramanik, A. Indian J. Chem. 2004, 43B, 595; (c) Das, S.; Koley, P.; Pramanik, A.
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2006, 207; (f) Das, S.; Fröhlich, R.; Pramanik, A. Org. Lett. 2006, 8, 4263; (g) Das,
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8.22 (d, J = 7.8 Hz, 1H), 7.94–7.84 (m, 3H), 7.29–7.19 (m, 10H), 6.29 (s, 1H); 13
C
NMR (75 MHz, DMSO-d6) d: 163.1, 157.0, 139.8, 129.7, 129.5, 129.1, 128.4,
127.9, 127.2, 126.9, 126.2, 122.2, 50.9; Anal. Calcd for C21H15NO2: C, 80.49; H,
4.82; N, 4.47. Found C, 80.38; H, 4.75; N, 4.41. 3-Benzhydryl-3-hydroxy-2-
phenylamino-2,3-dihydro-isoindol-1-one (3a): White solid (483 mg, 85%), mp
210–212 °C; IR (KBr): (cmꢀ1) 3302; 1686; NMR (300 MHz, CDCl3) d: 7.77 (d,
J = 7.1 Hz, 1H), 7.50 (d, J = 7.2 Hz, 1H), 7.46–7.37 (m, 3H), 7.29–7.22 (m, 3H),
7.18–7.12 (m, 5H), 6.87–6.74 (m, 5H), 6.67 (d, J = 7.5 Hz, 1H), 5.47 (s, 1H), 4.95
(s, 1H), 3.47 (s, 1H); 13C NMR (75 MHz, CDCl3) d: 166.4, 147.1, 143.6, 138.3,
138.0, 132.3, 130.6, 130.4, 130.1, 129.0, 129.0, 128.7, 128.0, 127.5, 127.2, 124.6,
123.7, 121.2, 114.0, 92.2, 58.3; Anal. Calcd for C27H22N2O2: C, 79.78; H, 5.46; N,
6.89. Found C, 79.66; H, 5.40; N, 6.82.
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