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

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

Key indicators

• Single-crystal X-ray study
• T = 168 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.052
• wR factor = 0.088
• Data-to-parameter ratio = 10.0

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

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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; ν_max (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,); ¹³C NMR (CDCl₃, 50 MHz): δ 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).

S3. Refinement

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

Computing details

Data collection: XSCANS (Bruker, 1997); cell refinement: XSCANS; data reduction: Xtal3.7 ADDREF SORTRF (Hall et al., 2000); program(s) used to solve structure: SIR97 (Altomare et al., 1994); program(s) used to refine structure: Xtal3.7 CRYLSQ; molecular graphics: Xtal3.7; software used to prepare material for publication: Xtal3.7 BONDLA CIFIO.

Figures

Fig. 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	Z = 2
Mr = 326.31	F(000) = 340
Triclinic, P1	Dx = 1.466 Mg m^−3
Hall symbol: -P 1	Melting point = 200–202 K
a = 7.868 (4) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.489 (4) Å	Cell parameters from 2508 reflections
c = 12.281 (6) Å	θ = 2.7–26.0°
α = 104.38 (1)°	µ = 0.11 mm^−1
β = 92.30 (1)°	T = 168 K
γ = 110.07 (1)°	Plate, yellow
V = 739.2 (6) Å^3	0.57 × 0.05 × 0.04 mm

Data collection

Bruker P4 diffractometer	Rint = 0.03
ω scans	θmax = 26.3°, θmin = 2.7°
9625 measured reflections	h = −9→9
2989 independent reflections	k = −10→9
2173 reflections with F^2 > σ(F^2)	l = −15→15

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	0 constraints
R[F^2 > 2σ(F^2)] = 0.052	H-atom parameters not refined
wR(F^2) = 0.088	w = 1/[σ^2(Fo^2) + (0.04Fo^2)^2]^1/2
S = 1.01	(Δ/σ)max < 0.001
2173 reflections	Δρmax = 0.35 e Å^−3
217 parameters	Δρmin = −0.43 e Å^−3

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

	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*
H12a	0.17466	1.16653	0.43268	0.06800*
H12b	0.18506	0.99741	0.45431	0.06800*
H12c	0.01857	0.98822	0.37748	0.06800*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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
C2—C3	1.395 (3)	C15—C16	1.386 (3)
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
C18—H18···N1	0.95	2.33	2.967 (3)	124