N-(4-Meth­oxy-2-methyl-5-nitro­phen­yl)acetamide

Uppu, R.M.; Fronczek, F.R.

doi:10.1107/S2414314625004705

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 10| Part 6| June 2025| x250470

https://doi.org/10.1107/S2414314625004705

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N-(4-Methoxy-2-methyl-5-nitrophenyl)acetamide

Rao M. Uppu ^a ^* and Frank R. Fronczek ^b

^aDepartment of Environmental Toxicology, Southern University and A&M College, Baton Rouge, LA 70813, USA, and ^bDepartment of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
^*Correspondence e-mail: [email protected]

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 23 May 2025; accepted 24 May 2025; online 3 June 2025)

In the title compound, C₁₀H₁₂N₂O₄, the four substituents lie out of the phenyl plane by varying degrees. The methyl C atom lies 0.019 (3) Å out of plane, while the methoxy O and C atoms lie 0.067 (2) and 0.042 (3) Å out of plane, respectively, with the C—C—O—C torsion angle being 3.3 (2)°. The plane of the nitro group is twisted out of the phenyl plane, forming a dihedral angle of 12.03 (9)° with it. The acetamide substituent is twisted considerably more out of the phenyl plane, forming a dihedral angle of 47.24 (6)° with it. In the extended structure, the acetamide NH group donates a hydrogen bond to an acetamide carbonyl O atom, thereby forming chains propagating in the [010] direction.

Keywords: crystal structure; alkoxyacetanilides; nonenzymatic biotransformation; peroxynitrite; xenobiotics.

CCDC reference: 2453807

Structure description

The title compound, C₁₀H₁₂N₂O₄, is a nitro-derivative of 2-methylmethacetin [N-(4-methoxy-2-methylphenyl)acetamide]. It is likely formed during peroxynitrite-mediated oxidation of 2-methylmethacetin under physiologically relevant pH and bicarbonate conditions (Hines et al., 2025 ). The reaction is consistent with electrophilic nitration initiated by the in situ generation of the free-radical oxidants nitrogen dioxide (^.NO₂) and carbonate radical (CO₃^.−) from the interaction of the peroxynitrite anion (ONOO⁻) with CO₂ (Agu et al., 2020 ; Deere et al., 2020 ; Lymar & Hurst, 1995 ; Uppu et al., 2000 ; Uppu & Pryor, 1996 ; Uppu & Pryor, 1999 ).

Phenacetin [N-(4-ethoxyphenyl)acetamide, C₁₀H₁₃NO₂], methacetin [N-(4-methoxyphenyl)acetamide, C₉H₁₁NO₂] and propacetin [N-(4-propoxyphenyl)acetamide, C₁₁H₁₅NO₂] were among the earliest synthetic antipyretic–analgesic agents examined in depth (Merck, 1899 ). Interest in these congeners grew after their precursor acetanilide (Antifebrin, introduced in 1880) was linked to methemoglobinaemia and cyanosis owing to excessive formation of its aniline metabolite. Comparative studies in the late 19th and early 20th centuries showed that methacetin possessed the strongest antipyretic and analgesic activity, followed by phenacetin and then propacetin, each acting through metabolic release of 4-aminophenol (Starmer et al., 1971 ). While all three function largely as pro-drugs, undergoing rapid oxidative O-dealkylation to produce the active metabolite 4-hydroxyacetanilide (Brodie & Axelrod, 1948 ; Kapetanović et al., 1979 ; Kapetanović & Mieyal, 1979 ), a minor N-deacetylation pathway yields 4-alkoxyanilines that can be further oxidized to reactive 4-N-hydroxy and 4-nitroso derivatives, leading to methemoglobinaemia, nephrotoxicity and, in the case of phenacetin, urothelial cancer (Prescott, 1980 ; Hinson, 1983 ). Toxicological studies in experimental animals revealed that methacetin, with the shortest alkyl chain, exhibited higher toxicity, while phenacetin, with a moderate chain length, offered a better balance between efficacy and reduced toxicity (Starmer et al., 1971). Consequently, phenacetin remained widely used until it was ultimately replaced by acetaminophen [N-(4-hydroxyphenyl)acetamide] in the 1980s as a safer alternative [FDA (Food and Drug Administration), 1983 ; IARC (International Agency for Research on Cancer), 1987 ]. There is no evidence that 2-methylmethacetin itself was ever marketed or tested in humans during that era (Merck, 1952 ). Recent studies show that oxidative O-demethylation of methacetin-(methyl-¹³C) and subsequent conversion of H¹³CHO to ¹³CO₂ in LiMAx/MBT breath testing provide broad diagnostic utility across diverse clinical applications (Buechter & Gerken, 2022 ; Gairing et al., 2022 ; Santol et al., 2024 ).

Non-enzymatic oxidation of 4-alkoxyacetanilides was largely unexplored until reactive oxygen and nitrogen species (RONS) were shown to nitrate 4-hydroxyacetanilide in vitro (Uppu & Martin, 2005 ; Deere et al., 2020). We reasoned that analogous reactions might affect other 4-alkoxy congeners. Indeed, treating 2-methylmethacetin with peroxynitrite in bicarbonate-enriched buffers at and around neutral pH yielded the title compound as the major product (Hines et al., 2025). The electron-donating 4-methoxy group directs nitration ortho to itself, whereas the acetamido group weakly deactivates the ring ortho to the amide; consequently, nitration occurs preferentially at C5 to give N-(4-methoxy-2-methyl-5-nitrophenyl)acetamide rather than the C6 position with little or no detectable formation of N-(4-methoxy-2-methyl-6-nitrophenyl)acetamide (Hines et al., 2025; Uppu & Martin, 2005). Towards better understanding of the mechanisms of electrophilic nitration of 4-alkoxyacetanilides by free radical oxidants formed in peroxynitrite/CO₂ reactions (Uppu & Pryor, 1999; Uppu et al., 2000) and to shed light on molecular targets, we grew crystals of N-(4-methoxy-2-methyl-5-nitrophenyl)acetamide in water and analyzed them by X-ray diffraction.

Single-crystal X-ray diffraction confirms this regiochemistry. The molecular structure (Fig. 1) shows the C1–C6 aromatic ring, methoxy group (C1–O1–C10H₃) and C9 methyl carbon atom to be nearly coplanar (r.m.s. deviation = 0.012 Å), whereas the N2/O3/O4 nitro group at C2 is twisted about the C2—N2 bond such that the plane of the nitro group forms a dihedral angle of 12.03 (9)° with the phenyl plane. The N1/C7/C8/O2 acetamide substituent is twisted considerably more out of the phenyl plane, forming a dihedral angle of 47.24 (6)° with it. In the crystal, N1—H1N⋯O2(carbonyl) hydrogen bonds [N⋯O = 2.8636 (16) Å] assemble the molecules into [010] chains (Table 1, Fig. 2); weaker C—H⋯O contacts link these chains into layers, giving the overall packing illustrated in Fig. 3. The 2-methyl substituent takes no part in specific intermolecular interactions but influences packing through van der Waals contacts.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯O2ⁱ	0.84 (2)	2.03 (2)	2.8636 (16)	174 (2)
C9—H9A⋯O2ⁱⁱ	0.98	2.54	3.5009 (19)	166
C9—H9B⋯O2ⁱ	0.98	2.47	3.2971 (19)	142
Symmetry codes: (i) $[-x+{\script{1\over 2}}, y-{\script{1\over 2}}, z]$ ; (ii) $[x+{\script{1\over 2}}, y, -z+{\script{3\over 2}}]$ .

Figure 1
The asymmetric unit of the title compound with 50% probability ellipsoids.

Figure 2
Fragment of a [010] hydrogen-bonded chain.

Figure 3
The unit cell. Only N-bound hydrogen atoms are shown.

The structure of the title compound represents the first crystallographic characterization of a nitrated 4-alkoxyacetanilide formed under biomimetic RONS conditions. Its isolation in peroxynitrite/CO₂-mediated oxidation of N-(4-methoxy-2-methyl)acetamide strongly suggests the possibility that analogous nitrated metabolites may arise in vivo during oxidative stress, potentially modulating the pharmacology or toxicity of 4-alkoxyacetanilide analgesics.

In terms of molecular planarity and substituent orientations, N-(4-methoxy-2-nitrophenyl)acetamide (Hines et al., 2022 ), N-(4-methoxy-3-nitrophenyl)acetamide (Hines et al., 2023 ) and the title compound share a benzene ring with the para-methoxy group nearly coplanar to it (C—C—O—C torsion angles on the order of 0–6°). Significant differences emerge in the disposition of the nitro and acetamide substituents. For instance, in N-(4-methoxy-3-nitrophenyl)acetamide, the acetamide moiety lies essentially in the aromatic plane (the C—N—C=O dihedral angle is close to 0°), making the entire methoxyphenyl-acetamide fragment nearly planar (r.m.s. deviation ∼0.04 Å). The nitro group at the meta position is rotated out of the ring plane (∼30°) and is disordered over two orientations. In N-(4-methoxy-3-nitrophenyl)acetamide and N-(4-methoxy-2-methyl-5-nitrophenyl)acetamide, with the nitro substituent ortho to the anilide nitrogen atom, the phenyl and acetamide groups are not coplanar. The acetamide group is tilted by about 25° in N-(4-methoxy-2-nitrophenyl)acetamide and as much as ∼47° in N-(4-methoxy-2-methyl-5-nitrophenyl)acetamide, due to steric interference from the ortho substituents. Meanwhile, their nitro groups (designated as either 2- or 5-position on the ring) are only moderately twisted out of the plane (on the order of 12°), a considerably smaller deviation than in N-(4-methoxy-3-nitrophenyl)acetamide.

Regarding intermolecular interactions, the presence or absence of an ortho nitro group governs the hydrogen-bonding patterns. In the 2-nitro compound [N-(4-methoxy-2-nitrophenyl)acetamide] (Hines et al., 2022), an intramolecular N—H⋯O hydrogen bond links the amide N—H group to the ortho nitro oxygen atom. This internal hydrogen bond satisfies the donor, so no strong intermolecular N—H bonds occur; instead, packing is consolidated by weaker contacts (e.g., a C—H⋯O contact between molecules) and exhibits a herringbone motif (adjacent phenyl rings are inclined by ∼65° rather than stacked parallel). In the 3-nitro isomer [N-4-methoxy-3-nitrophenyl)acetamide] (Hines et al., 2023), in contrast, there is no provision for an intramolecular hydrogen bond. Accordingly, each N—H group donates to a nitro oxygen atom on a neighboring molecule, forming N—H⋯O(nitro) chains in the crystal (the amide carbonyl O is not an acceptor in this structure). The 2-methyl-5-nitro derivative lacks an ortho nitro acceptor, and it instead exhibits the conventional amide catemer: the N—H hydrogen bonds to the carbonyl O atom of an adjacent molecule, linking molecules into N—H⋯O=C chains propagating through the structure. Importantly, none of nitro derivatives shows significant π–π stacking between aromatic rings; for example, the 2-nitro and 2-methyl-5-nitro crystals adopt a crossed herringbone-like packing rather than face-to-face stacks.

Synthesis and crystallization

N-(4-Methoxy-2-methyl-5-nitrophenyl)acetamide (CAS 196194–97-5), was obtained from AmBeed (Arlington Heights, Illinois, USA) and was used without further purification. Crystals in the form of colorless laths were prepared by slow cooling of a nearly saturated solution of the title compound in boiling deionized water (resistance ca. 18 MΩ.cm⁻¹).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₀H₁₂N₂O₄
M_r	224.22
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	100
a, b, c (Å)	14.2323 (6), 7.6198 (3), 19.8463 (8)
V (Å³)	2152.28 (15)
Z	8
Radiation type	Cu Kα
μ (mm⁻¹)	0.92
Crystal size (mm)	0.23 × 0.04 × 0.02

Data collection
Diffractometer	Bruker D8 Venture DUO with Photon III C14
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.722, 0.982
No. of measured, independent and observed [I > 2σ(I)] reflections	25336, 2301, 1853
R_int	0.160
(sin θ/λ)_max (Å⁻¹)	0.638

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.053, 0.136, 1.04
No. of reflections	2301
No. of parameters	151
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.37, −0.41
Computer programs: APEX5 and SAINT (Bruker, 2016 ), SHELXT2018/2 (Sheldrick, 2015a ), SHELXL2019/1 (Sheldrick, 2015b ), Mercury (Macrae et al., 2020 ), publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 2453807

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314625004705/hb4520sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314625004705/hb4520Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314625004705/hb4520Isup3.cml

checkCIF report

Computing details top

N-(4-Methoxy-2-methyl-5-nitrophenyl)acetamide top

Crystal data top

C₁₀H₁₂N₂O₄	D_x = 1.384 Mg m⁻³
M_r = 224.22	Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, Pbca	Cell parameters from 8628 reflections
a = 14.2323 (6) Å	θ = 4.5–79.4°
b = 7.6198 (3) Å	µ = 0.92 mm⁻¹
c = 19.8463 (8) Å	T = 100 K
V = 2152.28 (15) Å³	Lath, colourless
Z = 8	0.23 × 0.04 × 0.02 mm
F(000) = 944

Data collection top

Bruker D8 Venture DUO with Photon III C14 diffractometer	1853 reflections with I > 2σ(I)
Radiation source: IµS 3.0 microfocus	R_int = 0.160
φ and ω scans	θ_max = 79.5°, θ_min = 4.5°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −18→16
T_min = 0.722, T_max = 0.982	k = −9→9
25336 measured reflections	l = −24→25
2301 independent reflections

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.053	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.136	w = 1/[σ²(F_o²) + (0.0839P)² + 0.5117P] where P = (F_o² + 2F_c²)/3
S = 1.04	(Δ/σ)_max = 0.001
2301 reflections	Δρ_max = 0.37 e Å⁻³
151 parameters	Δρ_min = −0.41 e Å⁻³
0 restraints

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. All H atoms were located in difference maps and those on C were thereafter treated as riding in geometrically idealized positions with C—H distances 0.95 Å for phenyl and 0.98 Å for methyl. Coordinates of the N—H atom were refined. U_iso(H) values were assigned as 1.2U_eq for the attached atom (1.5 for methyl). Torsional parameters were refined for the methyl groups.

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

	x	y	z	U_iso*/U_eq
O1	0.34418 (8)	0.78233 (14)	0.55179 (6)	0.0238 (3)
O2	0.14170 (7)	0.65326 (13)	0.83184 (5)	0.0199 (3)
O3	0.16525 (11)	0.7593 (3)	0.52701 (8)	0.0556 (5)
O4	0.07202 (8)	0.71866 (19)	0.61014 (6)	0.0326 (3)
N1	0.25448 (9)	0.46222 (15)	0.79712 (6)	0.0173 (3)
H1N	0.2850 (15)	0.370 (3)	0.8043 (11)	0.021*
N2	0.15115 (9)	0.72149 (17)	0.58592 (7)	0.0222 (3)
C1	0.32443 (10)	0.70066 (17)	0.61038 (7)	0.0177 (3)
C2	0.23007 (10)	0.67361 (18)	0.62915 (7)	0.0169 (3)
C3	0.20741 (9)	0.59707 (17)	0.69062 (7)	0.0159 (3)
H3	0.143309	0.580561	0.702360	0.019*
C4	0.27693 (10)	0.54469 (17)	0.73487 (7)	0.0154 (3)
C5	0.37149 (10)	0.56655 (18)	0.71717 (7)	0.0181 (3)
C6	0.39333 (10)	0.64377 (18)	0.65543 (8)	0.0192 (3)
H6	0.457538	0.658219	0.643570	0.023*
C7	0.18799 (10)	0.51835 (18)	0.84076 (7)	0.0174 (3)
C8	0.17255 (12)	0.4061 (2)	0.90199 (8)	0.0263 (3)
H8A	0.221118	0.315107	0.904041	0.039*
H8B	0.110504	0.350799	0.899344	0.039*
H8C	0.175971	0.479260	0.942536	0.039*
C9	0.44939 (11)	0.5085 (2)	0.76307 (9)	0.0274 (4)
H9A	0.510092	0.538858	0.742883	0.041*
H9B	0.445817	0.381196	0.769593	0.041*
H9C	0.443105	0.567589	0.806702	0.041*
C10	0.44162 (13)	0.8017 (3)	0.53463 (8)	0.0313 (4)
H10A	0.447058	0.860973	0.490986	0.047*
H10B	0.471040	0.685593	0.531880	0.047*
H10C	0.473279	0.871596	0.569293	0.047*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0276 (6)	0.0242 (6)	0.0196 (5)	−0.0065 (4)	0.0059 (4)	0.0035 (4)
O2	0.0197 (5)	0.0166 (5)	0.0235 (5)	0.0003 (4)	0.0032 (4)	0.0017 (4)
O3	0.0339 (7)	0.1045 (14)	0.0285 (7)	0.0073 (8)	0.0004 (5)	0.0335 (8)
O4	0.0196 (6)	0.0494 (8)	0.0288 (6)	0.0028 (5)	−0.0025 (4)	0.0087 (5)
N1	0.0186 (6)	0.0131 (6)	0.0201 (6)	0.0017 (4)	0.0001 (4)	0.0031 (4)
N2	0.0238 (6)	0.0227 (6)	0.0203 (6)	0.0004 (5)	−0.0014 (5)	0.0045 (5)
C1	0.0230 (7)	0.0121 (6)	0.0182 (6)	−0.0033 (5)	0.0036 (5)	−0.0009 (5)
C2	0.0192 (7)	0.0138 (6)	0.0177 (6)	0.0008 (5)	−0.0007 (5)	0.0009 (5)
C3	0.0162 (6)	0.0130 (6)	0.0185 (6)	−0.0010 (5)	0.0015 (5)	0.0002 (5)
C4	0.0171 (7)	0.0105 (6)	0.0185 (7)	−0.0014 (5)	0.0011 (5)	0.0002 (4)
C5	0.0172 (7)	0.0136 (6)	0.0235 (7)	−0.0025 (5)	−0.0011 (5)	−0.0006 (5)
C6	0.0161 (6)	0.0165 (6)	0.0251 (7)	−0.0035 (5)	0.0033 (5)	−0.0015 (5)
C7	0.0180 (6)	0.0144 (6)	0.0198 (6)	−0.0036 (5)	−0.0002 (5)	−0.0001 (5)
C8	0.0339 (8)	0.0213 (7)	0.0236 (7)	0.0013 (6)	0.0056 (6)	0.0052 (6)
C9	0.0170 (7)	0.0314 (8)	0.0340 (8)	−0.0035 (6)	−0.0047 (6)	0.0080 (6)
C10	0.0318 (9)	0.0375 (9)	0.0245 (7)	−0.0168 (7)	0.0098 (6)	−0.0017 (6)

Geometric parameters (Å, º) top

O1—C1	1.3485 (17)	C4—C5	1.4009 (19)
O1—C10	1.436 (2)	C5—C6	1.394 (2)
O2—C7	1.2338 (18)	C5—C9	1.502 (2)
O3—N2	1.221 (2)	C6—H6	0.9500
O4—N2	1.225 (2)	C7—C8	1.502 (2)
N1—C7	1.3522 (19)	C8—H8A	0.9800
N1—C4	1.4224 (17)	C8—H8B	0.9800
N1—H1N	0.84 (2)	C8—H8C	0.9800
N2—C2	1.4597 (19)	C9—H9A	0.9800
C1—C6	1.396 (2)	C9—H9B	0.9800
C1—C2	1.409 (2)	C9—H9C	0.9800
C2—C3	1.3902 (19)	C10—H10A	0.9800
C3—C4	1.3818 (19)	C10—H10B	0.9800
C3—H3	0.9500	C10—H10C	0.9800

C1—O1—C10	116.96 (13)	C5—C6—H6	118.8
C7—N1—C4	125.01 (12)	C1—C6—H6	118.8
C7—N1—H1N	121.3 (15)	O2—C7—N1	123.05 (13)
C4—N1—H1N	113.7 (15)	O2—C7—C8	120.82 (13)
O3—N2—O4	122.09 (14)	N1—C7—C8	116.13 (13)
O3—N2—C2	119.70 (14)	C7—C8—H8A	109.5
O4—N2—C2	118.20 (13)	C7—C8—H8B	109.5
O1—C1—C6	123.30 (13)	H8A—C8—H8B	109.5
O1—C1—C2	119.62 (14)	C7—C8—H8C	109.5
C6—C1—C2	117.06 (13)	H8A—C8—H8C	109.5
C3—C2—C1	120.96 (13)	H8B—C8—H8C	109.5
C3—C2—N2	116.25 (12)	C5—C9—H9A	109.5
C1—C2—N2	122.79 (13)	C5—C9—H9B	109.5
C4—C3—C2	120.86 (13)	H9A—C9—H9B	109.5
C4—C3—H3	119.6	C5—C9—H9C	109.5
C2—C3—H3	119.6	H9A—C9—H9C	109.5
C3—C4—C5	119.62 (13)	H9B—C9—H9C	109.5
C3—C4—N1	121.25 (12)	O1—C10—H10A	109.5
C5—C4—N1	119.08 (13)	O1—C10—H10B	109.5
C6—C5—C4	118.99 (13)	H10A—C10—H10B	109.5
C6—C5—C9	119.53 (13)	O1—C10—H10C	109.5
C4—C5—C9	121.48 (13)	H10A—C10—H10C	109.5
C5—C6—C1	122.49 (13)	H10B—C10—H10C	109.5

C10—O1—C1—C6	3.3 (2)	C2—C3—C4—N1	−178.38 (12)
C10—O1—C1—C2	−178.34 (13)	C7—N1—C4—C3	−46.4 (2)
O1—C1—C2—C3	−177.04 (12)	C7—N1—C4—C5	136.18 (15)
C6—C1—C2—C3	1.4 (2)	C3—C4—C5—C6	1.1 (2)
O1—C1—C2—N2	3.6 (2)	N1—C4—C5—C6	178.54 (12)
C6—C1—C2—N2	−177.98 (13)	C3—C4—C5—C9	−178.84 (14)
O3—N2—C2—C3	−166.83 (17)	N1—C4—C5—C9	−1.4 (2)
O4—N2—C2—C3	11.7 (2)	C4—C5—C6—C1	0.1 (2)
O3—N2—C2—C1	12.6 (2)	C9—C5—C6—C1	179.99 (14)
O4—N2—C2—C1	−168.90 (14)	O1—C1—C6—C5	177.07 (13)
C1—C2—C3—C4	−0.3 (2)	C2—C1—C6—C5	−1.3 (2)
N2—C2—C3—C4	179.11 (12)	C4—N1—C7—O2	−2.9 (2)
C2—C3—C4—C5	−1.0 (2)	C4—N1—C7—C8	177.03 (13)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O2ⁱ	0.84 (2)	2.03 (2)	2.8636 (16)	174 (2)
C9—H9A···O2ⁱⁱ	0.98	2.54	3.5009 (19)	166
C9—H9B···O2ⁱ	0.98	2.47	3.2971 (19)	142

Symmetry codes: (i) −x+1/2, y−1/2, z; (ii) x+1/2, y, −z+3/2.

Funding information

The authors acknowledge support from the National Institute of General Medical Sciences of the National Institutes of Health (P20 GM103424–21), the U.S. Department of Education (P031B040030), and the National Science Foundation (2418415 RII FEC and CHE-2215262). The contents of this manuscript are solely the responsibility of the authors and do not represent the official views of these funding agencies.

References

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