Ethyl 6 nitro 2 phenyl­amino­imidazo­[1,2 a]­pyridine 3 carboxyl­ate

organic papers

o980

Acta Crystallographica Section E Structure Reports Online

ISSN 1600-5368

Ethyl 6-nitro-2-phenylaminoimidazo[1,2-

a

]pyridine-3-carboxylate

David W. Jeffery, Rolf H. Prager and Max R. Taylor*

School of Chemistry, Physics and Earth Sciences, The Flinders University of South Australia, GPO Box 2100, Adelaide, SA 5048, Australia

Correspondence e-mail: max.taylor@flinders.edu.au

Key indicators

Single-crystal X-ray study

T= 168 K

Mean(C±C) = 0.003 AÊ

Rfactor = 0.052

wRfactor = 0.088

Data-to-parameter ratio = 10.0

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

#2001 International Union of Crystallography Printed in Great Britain ± all rights reserved

In crystals of the title compound, C16H14N4O4, the molecule is found in an extended near-planar conformation, stabilized by intramolecular attractive interactions and electron delocaliza-tion. This analysis establishes an otherwise ambiguous spectroscopic assignment of the structure.

Comment

We have reported that brief photolysis or ¯ash vacuum pyrolysis of the nitropyridylisoxazolone (1) gives a good yield of the indole (2) (Khalafyet al., 1999) arising from the intra-molecular cyclization of the carbene intermediate. Subse-quently, we found that reaction of the isoxazolone (1) with a weak base in ethanol gave the same compound (2), by a sequence that is mechanistically different, and clearly incom-patible with a carbenoid intermediate (Khalafy & Prager, 2000). During an extension of the latter reaction to a number of arylamino analogues, we encountered substrates that led to the formation of two products, one of which was analogous to the indole (2), and the other to the isomeric ethyl 6-nitro-2-phenylaminoimidazo[1,2-a]pyridine-3-carboxylate, (3). After comparison of the spectroscopic properties of the indole and imidazopyridine compounds, we suspected that the structure of the product (2) had been misassigned and that the product of all three reactions of (1) was the imidazopyridine (3). This suspicion has been clearly con®rmed by the crystal structure determination of (3).

In the crystal structure of the title compound, (3), the molecule is ¯at with all the non-H atoms within0.19 AÊ of a

common plane (Fig. 1). This conformation is clearly stabilized by three attractive intramolecular contacts detailed in Table 2. This conformation is further stabilized by the electron delo-calization that occurs. Seven CÐN bonds in the molecule (omitting N2ÐC6) are of similar length, ranging from 1.328 (3) to 1.405 (3) AÊ, with C2ÐN3 notably 1.353 (3) AÊ (Table 1). Therefore, the C2ÐN3 bond has signi®cant double-bond character which in turn would lead to higher acidity for H3 and a stronger N3ÐH O3 hydrogen bond (Table 2). The molecules are arranged in sheets throughout the structure parallel to (212) and about 3.3 AÊ apart. There is an angle of 3.07 (7) _{between the planes of the nitro group (C6, N2, O1}

and O2) and the imidazopyridine moiety. There are 26 distinct examples of this imidazopyridine moiety, substituted in a variety of ways, in the April 2001 version of the Cambridge Structural Database (Allen & Kennard, 1993).

Experimental

Ethyl 2-(5-nitropyridin-2-yl)-5-oxo-3-phenylamino-2,5-dihydro-isoxazole-4-carboxylate (Khalafyet al., 1999) (0.020 g, 0.054 mmol) and potassium carbonate (0.037 g, 0.270 mmol) were re¯uxed in ethanol (2 ml) for 1 h. After 20 min the solution turned from orange to red. The solution was cooled, quenched with 1MHCl (5 ml) and extracted with CH2Cl2(3 25 ml). The combined extracts were

washed with brine (120 ml), dried (MgSO4) and the solvent was

removedin vacuo, yielding a red solid which was recrystallized from ethanol to give the title compound (3) as yellow needles (0.012 g, 67%): m.p. 473±475 K;max(®lm): 3330, 1667, 1619, 1604, 1576, 1344,

1310, 1212 cmÿ1_;1_{H NMR (CDCl}

3, 200 MHz):9.87,bs, 1H; 8.93,bs,

1H; 8.15,dd,J= 9.6, 2.1 Hz, 1H; 7.72,d,J= 7.8 Hz, 2H; 7.52,d,J= 9.6 Hz, 1H; 7.38,t,J= 7.8 Hz, 2H; 7.07,t,J= 7.8 Hz, 1H; 4.56,q, J= 7.1 Hz, 2H; 1.55,t,J= 7.1 Hz, 3H,);13_{C NMR (CDCl}

3, 50 MHz):

160.8, 147.0, 139.4, 137.0, 129.2, 126.9, 122.9, 122.4, 118.8, 114.0, 98.9, 61.1, 14.6 (one carbonyl unsighted);m/z: 326 (M, 100%), 280 (54), 234 (27), 206 (10), 130 (11), 104 (17), 103 (15), 77 (36), 51 (13), 44 (15).

Crystal data

C16H14N4O4

Mr= 326.31

Triclinic,P1

a= 7.868 (4) AÊ

b= 8.489 (4) AÊ

c= 12.281 (6) AÊ = 104.38 (1)

= 92.30 (1)

= 110.07 (1)

V= 739.2 (6) AÊ3

Z= 2

Dx= 1.466 Mg mÿ3

Mo Kradiation Cell parameters from 2508

re¯ections = 2.7±26.0

= 0.11 mmÿ1

T= 168 (2) K Plate, yellow

0.570.050.04 mm

Data collection

BrukerP4 diffractometer !scans

9625 measured re¯ections 2989 independent re¯ections 2173 re¯ections withF2_>(F2₎

Rint= 0.03

max= 26.3

h=ÿ9!9

k=ÿ10!9

l=ÿ15!15

Re®nement

Re®nement onF2

R[F2_>(F2_{)] = 0.052}

wR(F2_{) = 0.088}

S= 1.11 2173 re¯ections 217 parameters

H-atom parameters not re®ned

w= 1/[2_(F

o2) + (0.04Fo2)2]1/2

(/)max< 0.001

max= 0.35 e AÊÿ3

min=ÿ0.43 e AÊÿ3

Table 1

Selected bond lengths (AÊ).

O1ÐN2 1.233 (3)

O2ÐN2 1.224 (3)

N1ÐC9 1.329 (3)

N1ÐC2 1.362 (3)

N2ÐC6 1.448 (3)

N3ÐC2 1.353 (3)

N3ÐC13 1.402 (3)

N4ÐC5 1.355 (3)

N4ÐC3 1.398 (3)

N4ÐC9 1.405 (3)

C2ÐC3 1.395 (3)

C3ÐC10 1.431 (3)

C5ÐC6 1.358 (3)

C6ÐC7 1.397 (3)

C7ÐC8 1.355 (3)

C8ÐC9 1.403 (3)

Table 2

Hydrogen-bonding geometry (AÊ,_).

DÐH A DÐH H A D A DÐH A

N3ÐH3 O3 0.92 2.12 2.835 (2) 133

C5ÐH5 O4 0.95 2.28 2.832 (3) 116

C18ÐH18 N1 0.95 2.33 2.967 (3) 124

All H atoms were observed in a difference map but were placed at calculated positions.

Data collection: XSCANS (Bruker, 1997); cell re®nement: XSCANS; data reduction:Xtal3.7ADDREF SORTRF(Hallet al., 2000); program(s) used to solve structure: SIR97 (Altomare et al., 1994); program(s) used to re®ne structure:Xtal3.7CRYLSQ; mole-cular graphics:Xtal3.7; software used to prepare material for publi-cation:Xtal3.7BONDLA CIFIO.

We thank Dr Jan Wikaira of the University of Canterbury, Christchurch, New Zealand, for collecting the data.

References

Allen, F. H. & Kennard, O. (1993).Chem. Des. Autom. News,8, 1, 31±37. Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C.,

Polidori, G. & Camalli, M. (1994).J. Appl. Cryst.27, 435.

Acta Cryst.(2001). E57, o980±o982 David W Jefferyet al. C₁₆H₁₄N₄O₄

o981

organic papers

Figure 1

organic papers

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Bruker (1997). XSCANS. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.

Hall, S. R., du Boulay, D. J. & Olthof-Hazekamp, R. (2000). Editors.Xtal3.7

System. University of Western Australia, Perth: Lamb.

Khalafy, J. & Prager, R. H. (2000).J. Sci. I.R.Iran,11, 32±38.

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Acta Cryst. (2001). E57, o980–o982 [doi:10.1107/S1600536801015574]

Ethyl 6-nitro-2-phenylaminoimidazo[1,2-

a

]pyridine-3-carboxylate

David W. Jeffery, Rolf H. Prager and Max R. Taylor

S1. Comment

We have reported that brief photolysis or flash vacuum pyrolysis of the nitropyridylisoxazolone (1) gives a good yield of

the indole (2) (Khalafy et al., 1999) arising from the intramolecular cyclization of the carbene intermediate. Subsequently, we found that reaction of the isoxazolone (1) with a weak base in ethanol gave the same compound (2), by a sequence

that is mechanistically different, and clearly incompatible with a carbenoid intermediate (Khalafy & Prager, 2000).

During an extension of the latter reaction to a number of arylamino analogues, we encountered substrates that led to the

formation of two products, one of which was analogous to the indole (2), and the other to the isomeric ethyl

6-nitro-2-phenylaminoimidazo[1,2-a]pyridine-3-carboxylate, (3). After comparison of the spectroscopic properties of the indole and imidazopyridine compounds, we suspected that the structure of the product (2) had been misassigned and that the

product of all three reactions of (1) was the imidazopyridine (3). This suspicion has been clearly confirmed by the crystal

structure determination of (3).

In the crystal structure of the title compound, (3), the molecule is flat with all the non-H atoms within ±0.19 Å of a

common plane (Fig. 1). This conformation is clearly stabilized by three attractive intramolecular contacts detailed in

Table 2. This conformation is further stabilized by the electron delocalization that occurs. Seven C—N bonds in the

molecule (omitting N2—C6) are of similar length, ranging from1.328 (3) to 1.405 (3) Å, with C2—N3 notably 1.353 (3)

Å (Table 1). Therefore, the C2—N3 bond has significant double-bond character which in turn would lead to higher

acidity for H3 and a stronger N3—H···O3 hydrogen bond (Table 2). The molecules are arranged in sheets throughout the

structure parallel to (212) and about 3.3 Å apart. There is an angle of 3.07 (7)° between the planes of the nitro group (C6,

N2, O1 and O2) and the imidazopyridine moiety. There are 26 distinct examples of this imidazopyridine moiety,

substituted in a variety of ways, in the April, 2001 version of the Cambridge Structural Database (Allen & Kennard,

1993).

S2. Experimental

Ethyl 2-(5-nitropyridin-2-yl)-5-oxo-3-phenylamino-2,5-dihydroisoxazole-4-carboxylate (Khalafy et al., 1999) (0.020 g, 0.054 mmol) and potassium carbonate (0.037 g, 0.270 mmol) were refluxed in ethanol (2 ml) for 1 h. After 20 min the

solution turned from orange to red. The solution was cooled, quenched with 1 M HCl (5 ml) and extracted with CH2Cl2 (3

× 25 ml). The combined extracts were washed with brine (1 × 20 ml), dried (MgSO4) and the solvent was removed in

vacuo, yielding a red solid which was recrystallized from ethanol to give the title compound (3) as yellow needles (0.012 g, 67%): m.p. 473–475 K; νmax (film): 3330, 1667, 1619, 1604, 1576, 1344, 1310, 1212 cm-1; 1H NMR (CDCl3, 200

MHz): δ 9.87, bs, 1H; 8.93, bs, 1H; 8.15, dd, J = 9.6, 2.1 Hz, 1H; 7.72, d, J = 7.8 Hz, 2H; 7.52, d, J = 9.6 Hz, 1H; 7.38, t, J = 7.8 Hz, 2H; 7.07, t, J = 7.8 Hz, 1H; 4.56, q, J = 7.1 Hz, 2H; 1.55, t, J = 7.1 Hz, 3H,); 13_{C NMR (CDCl}

3, 50 MHz): δ

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S3. Refinement

All H atoms were observed in a difference map but were placed at calculated positions.

Figure 1

View of the title molecule, (3), showing the atom labels. Displacement ellipsoids are at the 50% probability level.

Ethyl 6-nitro-2-phenylaminoimidazo[1,2-a]pyridine-3-carboxylate

Crystal data

C16H14N4O4

Mr = 326.31

Triclinic, P1 Hall symbol: -P 1

a = 7.868 (4) Å

b = 8.489 (4) Å

c = 12.281 (6) Å

α = 104.38 (1)°

β = 92.30 (1)°

γ = 110.07 (1)°

V = 739.2 (6) Å3

Z = 2

F(000) = 340

Dx = 1.466 Mg m−3

Melting point = 200–202 K Mo Kα radiation, λ = 0.71073 Å Cell parameters from 2508 reflections

θ = 2.7–26.0°

µ = 0.11 mm−1

T = 168 K Plate, yellow

0.57 × 0.05 × 0.04 mm

Data collection

Bruker P4 diffractometer

ω scans

9625 measured reflections 2989 independent reflections 2173 reflections with F2 _{> σ(F}2₎

Rint = 0.03

θmax = 26.3°, θmin = 2.7°

h = −9→9

k = −10→9

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Refinement

Refinement on F2

Least-squares matrix: full

R[F2 _{> 2σ(F}2_{)] = 0.052}

wR(F2_{) = 0.088}

S = 1.01 2173 reflections 217 parameters

0 restraints 0 constraints

H-atom parameters not refined

w = 1/[σ2_(F

o2) + (0.04Fo2)2]1/2

(Δ/σ)max < 0.001

Δρmax = 0.35 e Å−3

Δρmin = −0.43 e Å−3

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2₎

x y z Uiso*/Ueq

O1 −0.2799 (2) 0.2258 (2) 0.41191 (14) 0.0495 (8) O2 −0.1648 (2) 0.5073 (2) 0.44612 (13) 0.0386 (8) O3 0.3638 (2) 0.87524 (19) 0.11382 (12) 0.0347 (7) O4 0.1937 (2) 0.83149 (18) 0.25432 (12) 0.0325 (7) N1 0.1324 (2) 0.3158 (2) −0.00132 (14) 0.0276 (8) N2 −0.1906 (2) 0.3598 (3) 0.38705 (16) 0.0328 (9) N3 0.3374 (2) 0.5649 (2) −0.05142 (15) 0.0287 (8)

N4 0.0750 (2) 0.4668 (2) 0.16308 (14) 0.0247 (8)

C2 0.2267 (3) 0.4901 (3) 0.01771 (18) 0.0261 (9)

C3 0.1960 (3) 0.5902 (3) 0.11813 (17) 0.0250 (9)

C5 0.0016 (3) 0.4851 (3) 0.26123 (18) 0.0261 (9)

C6 −0.1143 (3) 0.3379 (3) 0.28145 (18) 0.0269 (10) C7 −0.1617 (3) 0.1717 (3) 0.20586 (19) 0.0321 (10)

C8 −0.0836 (3) 0.1543 (3) 0.1095 (2) 0.0314 (10)

C9 0.0402 (3) 0.3024 (3) 0.08636 (18) 0.0261 (9)

C10 0.2604 (3) 0.7766 (3) 0.15997 (19) 0.0285 (10)

C11 0.2431 (3) 1.0191 (3) 0.2992 (2) 0.0374 (11)

C12 0.1466 (3) 1.0451 (3) 0.4000 (2) 0.0456 (12)

C13 0.3876 (3) 0.4878 (3) −0.15353 (17) 0.0257 (9) C14 0.5070 (3) 0.6015 (3) −0.20474 (19) 0.0295 (10) C15 0.5639 (3) 0.5360 (3) −0.3044 (2) 0.0330 (10) C16 0.5046 (3) 0.3576 (3) −0.35488 (19) 0.0337 (11) C17 0.3852 (3) 0.2461 (3) −0.30422 (19) 0.0338 (10) C18 0.3249 (3) 0.3085 (3) −0.20435 (18) 0.0303 (10)

H3 0.38760 0.68500 −0.02772 0.03600*

H5 0.03002 0.59664 0.31390 0.03300*

H7 −0.24704 0.07252 0.22192 0.04000*

H8 −0.11255 0.04201 0.05760 0.03900*

H14 0.54904 0.72409 −0.17082 0.03700*

H15 0.64531 0.61410 −0.33914 0.04100*

H16 0.54558 0.31297 −0.42348 0.04200*

H17 0.34349 0.12360 −0.33866 0.04200*

H18 0.24138 0.23001 −0.17079 0.03800*

H11a 0.37155 1.07461 0.32075 0.04700*

H11b 0.20506 1.06541 0.24390 0.04700*

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H12b 0.18506 0.99741 0.45431 0.06800*

H12c 0.01857 0.98822 0.37748 0.06800*

Atomic displacement parameters (Å2₎

U11 _U22 _U33 _U12 _U13 _U23

O1 0.0620 (12) 0.0368 (10) 0.0485 (11) 0.0099 (9) 0.0334 (9) 0.0174 (9) O2 0.0455 (10) 0.0331 (10) 0.0364 (10) 0.0150 (8) 0.0169 (8) 0.0055 (8) O3 0.0396 (10) 0.0262 (9) 0.0362 (9) 0.0078 (7) 0.0163 (8) 0.0097 (7) O4 0.0392 (9) 0.0210 (8) 0.0334 (9) 0.0080 (7) 0.0174 (7) 0.0033 (7) N1 0.0281 (10) 0.0262 (11) 0.0285 (11) 0.0087 (8) 0.0094 (9) 0.0083 (8) N2 0.0319 (11) 0.0343 (12) 0.0331 (12) 0.0113 (10) 0.0136 (9) 0.0107 (10) N3 0.0328 (11) 0.0212 (10) 0.0290 (11) 0.0064 (8) 0.0124 (9) 0.0055 (8) N4 0.0242 (10) 0.0233 (10) 0.0262 (10) 0.0077 (8) 0.0087 (8) 0.0066 (8) C2 0.0244 (12) 0.0260 (13) 0.0285 (13) 0.0093 (10) 0.0048 (10) 0.0081 (10) C3 0.0253 (12) 0.0251 (12) 0.0255 (13) 0.0087 (10) 0.0089 (10) 0.0086 (10) C5 0.0289 (12) 0.0268 (12) 0.0230 (12) 0.0117 (10) 0.0083 (10) 0.0047 (9) C6 0.0282 (12) 0.0310 (13) 0.0246 (12) 0.0133 (10) 0.0098 (10) 0.0086 (10) C7 0.0326 (13) 0.0261 (13) 0.0372 (15) 0.0076 (11) 0.0151 (12) 0.0111 (11) C8 0.0349 (13) 0.0204 (12) 0.0350 (14) 0.0072 (10) 0.0105 (11) 0.0043 (10) C9 0.0256 (12) 0.0261 (12) 0.0268 (12) 0.0107 (10) 0.0058 (10) 0.0059 (10) C10 0.0268 (12) 0.0297 (13) 0.0287 (13) 0.0101 (10) 0.0053 (11) 0.0077 (11) C11 0.0424 (14) 0.0220 (13) 0.0424 (15) 0.0070 (11) 0.0164 (12) 0.0046 (11) C12 0.0554 (16) 0.0311 (14) 0.0392 (15) 0.0077 (12) 0.0198 (13) −0.0001 (11) C13 0.0255 (12) 0.0294 (13) 0.0253 (12) 0.0130 (10) 0.0058 (10) 0.0088 (10) C14 0.0304 (13) 0.0259 (13) 0.0324 (14) 0.0095 (10) 0.0099 (11) 0.0089 (11) C15 0.0329 (13) 0.0332 (14) 0.0339 (14) 0.0097 (11) 0.0141 (11) 0.0131 (11) C16 0.0366 (14) 0.0381 (15) 0.0280 (13) 0.0155 (12) 0.0125 (11) 0.0078 (11) C17 0.0390 (14) 0.0295 (13) 0.0287 (13) 0.0098 (11) 0.0071 (11) 0.0041 (11) C18 0.0314 (13) 0.0283 (13) 0.0292 (13) 0.0074 (11) 0.0104 (11) 0.0088 (10)

Geometric parameters (Å, º)

O1—N2 1.233 (3) C7—C8 1.355 (3)

O2—N2 1.224 (3) C8—H8 0.951

O3—C10 1.220 (3) C8—C9 1.403 (3)

O4—C10 1.336 (3) C11—H11b 0.950

O4—C11 1.454 (3) C11—H11a 0.950

N1—C9 1.329 (3) C11—C12 1.488 (4)

N1—C2 1.362 (3) C12—H12b 0.950

N2—C6 1.448 (3) C12—H12c 0.950

N3—H3 0.920 C12—H12a 0.950

N3—C2 1.353 (3) C13—C18 1.392 (3)

N3—C13 1.402 (3) C13—C14 1.392 (3)

N4—C5 1.355 (3) C14—H14 0.951

N4—C3 1.398 (3) C14—C15 1.373 (3)

N4—C9 1.405 (3) C15—H15 0.950

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C3—C10 1.431 (3) C16—H16 0.951

C5—H5 0.951 C16—C17 1.376 (3)

C5—C6 1.358 (3) C17—H17 0.951

C6—C7 1.397 (3) C17—C18 1.381 (3)

C7—H7 0.951 C18—H18 0.950

C10—O4—C11 116.71 (18) O3—C10—C3 123.7 (2)

C9—N1—C2 105.10 (17) O4—C10—C3 112.9 (2)

O2—N2—O1 123.6 (2) H11b—C11—H11a 109.5

O2—N2—C6 119.27 (19) H11b—C11—O4 110.27

O1—N2—C6 117.08 (18) H11b—C11—C12 110.3

H3—N3—C2 114.99 H11a—C11—O4 110.3

H3—N3—C13 115.01 H11a—C11—C12 110.3

C2—N3—C13 130.00 (17) O4—C11—C12 106.15 (18)

C5—N4—C3 131.19 (17) H12b—C12—H12c 109.5

C5—N4—C9 122.07 (18) H12b—C12—H12a 109.5

C3—N4—C9 106.71 (17) H12b—C12—C11 109.5

N3—C2—N1 125.7 (2) H12c—C12—H12a 109.5

N3—C2—C3 121.48 (19) H12c—C12—C11 109.5

N1—C2—C3 112.8 (2) H12a—C12—C11 109.4

C2—C3—N4 103.88 (17) C18—C13—C14 119.8 (2)

C2—C3—C10 127.9 (2) C18—C13—N3 123.9 (2)

N4—C3—C10 128.0 (2) C14—C13—N3 116.26 (18)

H5—C5—N4 121.3 H14—C14—C15 120.1

H5—C5—C6 121.3 H14—C14—C13 120.1

N4—C5—C6 117.41 (18) C15—C14—C13 119.8 (2)

C5—C6—C7 123.2 (2) H15—C15—C14 119.5

C5—C6—N2 116.66 (18) H15—C15—C16 119.6

C7—C6—N2 120.1 (2) C14—C15—C16 120.9 (2)

H7—C7—C8 120.6 H16—C16—C17 120.5

H7—C7—C6 120.6 H16—C16—C15 120.5

C8—C7—C6 118.9 (2) C17—C16—C15 118.9 (2)

H8—C8—C7 120.1 H17—C17—C16 119.3

H8—C8—C9 120.1 H17—C17—C18 119.3

C7—C8—C9 119.83 (19) C16—C17—C18 121.3 (2)

N1—C9—C8 130.00 (19) H18—C18—C17 120.4

N1—C9—N4 111.50 (18) H18—C18—C13 120.4

C8—C9—N4 118.5 (2) C17—C18—C13 119.2 (2)

O3—C10—O4 123.4 (2)

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A

N3—H3···O3 0.92 2.12 2.835 (2) 133

C5—H5···O4 0.95 2.28 2.832 (3) 116