Different classical hydrogen-bonding patterns in three salicylaldoxime derivatives, 2-HO-4-XC6H3C=NOH (X = Me, OH and MeO).

The crystal structures of three salicyaldoxime compounds, namely 2-hy-droxy-4-methyl-benzaldehyde oxime, C8H9NO2, 1, 2,4-di-hydroxy-benzaldehyde oxime, C7H7NO3, 2, and 2-hy-droxy-4-meth-oxy-benzaldehyde oxime, C8H9NO3, 3, are discussed. In each compound, the hydroxyl groups are essentially coplanar with their attached phenyl group. The inter-planar angles between the C=N-O moieties of the oxime unit and their attached phenyl rings are 0.08 (9), 1.08 (15) and 6.65 (15)° in 1, 2 and 3, respectively. In all three mol-ecules, the 2-hy-droxy group forms an intra-molecular O-H⋯N(oxime) hydrogen bond. In compound (1), inter-molecular O-H(oxime)⋯O(hydrox-yl) hydrogen bonds generate R 2 2(14) dimers, related by inversion centres. In compound 2, inter-molecular O-H(oxime)⋯O(4-hy-droxy) hydrogen bonds generate C9 chains along the b-axis direction, while O-H(4-hydrox-yl)⋯O(2-hydrox-yl) inter-actions form zigzag C6 spiral chains along the c-axis direction, generated by a screw axis at 1, y, 1/4: the combination of the two chains provides a bimolecular sheet running parallel to the b axis, which lies between 0-1/2 c and 1/2-1 c. In compound 3, similar C9 chains, along the b-axis direction are generated by O-H(oxime)⋯O(4-meth-oxy) hydrogen bonds. Further weaker, C-H⋯π (in 1), π-π (in 2) and both C-H⋯π and π-π inter-actions (in 3) further cement the three-dimensional structures. Hirshfeld surface and fingerprint analyses are discussed.

Chemical context

Aldoximes, RCH=NOH, are found in many biologically active compounds (Abele et al., 2008 ▸; Nikitjuka & Jirgensons 2014 ▸), having a diverse range of uses including as anti-tumor agents (Martínez-Pascual et al., 2017 ▸; Qin et al., 2017 ▸; Canario et al., 2018 ▸; Huang et al., 2018 ▸), acaricidal and insecticidal agents (Dai et al., 2017 ▸), thymidine phospho­rylase inhibitors (Zhao et al., 2018 ▸), anti-microbial agents (Yadav et al., 2017 ▸), bacteriocides (Kozlowska et al., 2017 ▸), anti-inflammatory agents (Mohassab et al., 2017 ▸) and in the treatment of nerve-gas poisoning (Lorke et al., 2008 ▸; Voicu et al., 2010 ▸; Katalinić et al., 2017 ▸; Radić et al., 2013 ▸). In the plant kingdom, oximes play a vital role in metabolism (Sørensen et al., 2018 ▸). A specific inter­est in 2-hydroxbenzaldehyde derivatives has arisen regarding their use as ligands for metal complexation (Wood et al., 2006 ▸, 2008b ▸).

The compounds described herein are all salicylaldoxime derivatives (2-HO-4-X-C6H3-CH=NOH) with different substituents in the 4-position, namely a methyl group, a hy­droxy group and a meth­oxy group, respectively, in compounds, 1, 2 and 3. A frequent finding for salicylaldoxime derivatives is the formation of inversion-related (14) dimers, as concluded from a Cambridge Structural Database survey (CSD Version 5.39, May 2018 update; Groom et al., 2016 ▸). While the structures of many salicylaldoxime derivatives have been reported, the structures of very few compounds with an additional substituent in the 4 position are known.

Compounds 1 and 3 have been shown to have significant activity against Mycobacterium tuberculosis ATTC 27294. The full report will be published elsewhere (da Costa et al., 2018 ▸).

Structural commentary

There are no unusual features in the mol­ecular structures. Compound 1 (Fig. 1 ▸) crystallizes in the monoclinic space group P21/n with one mol­ecule in the asymmetric unit. Compounds 2 and 3 crystallize in the monoclinic space group P21/c with one mol­ecule in the asymmetric unit (Figs. 2 ▸ and 3 ▸), all having an oxime unit with an (E) geometry. Bond angles and bond lengths in the phenyl and oxime fragments are all in the expected ranges.

Figure 1

The mol­ecular structure of compound 1, showing 80% displacement ellipsoids.

Figure 2

The mol­ecular structure of compound 2, showing 80% displacement ellipsoids.

Figure 3

The mol­ecular structure of compound 3, showing 80% displacement ellipsoids.

In compound 1, the hydroxyl group is essentially coplanar with its attached phenyl group [displaced by 0.020 (1) Å], while the inter­planar angle between the C=NO moiety of the oxime unit and the attached phenyl rings is 0.08 (9)°. In compound 2, the hydroxyl groups lie essentially within the phenyl ring plane [O atoms deviate by −0.003 (1) and 0.006 (1) Å], while the inter­planar angle between the C=NO moiety of the oxime unit and the attached phenyl rings is 1.08 (15)°. In compound 3, the inter­planar angle between the C=NO moiety of the oxime unit and the attached phenyl rings is 6.65 (15)°.

In all three mol­ecules, an intra­molecular O2—H2⋯N12 hydrogen bond (Tables 1 ▸–3 ▸ ▸) forms a pseudo six-membered ring.

Table 1

Hydrogen-bond geometry (Å, °) for 1

Cg is the centroid of the C1–C6 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯N12	0.879 (18)	1.814 (18)	2.6066 (10)	149.0 (15)
O13—H13⋯O2i	0.857 (17)	2.019 (17)	2.8132 (9)	153.7 (15)
O13—H13⋯O13ii	0.857 (17)	2.611 (16)	2.8961 (14)	100.8 (12)
C3—H3⋯Cg iii	0.95	2.71	3.4577 (9)	136
C11—H11⋯Cg iv	0.95	2.73	3.4910 (9)	138

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

Table 2

Hydrogen-bond geometry (Å, °) for 2

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯N12	0.91 (3)	1.77 (3)	2.5899 (17)	150 (2)
O4—H4⋯O2i	0.86 (2)	1.85 (2)	2.7062 (16)	174 (2)
O13—H13⋯O4ii	0.86 (3)	1.90 (3)	2.7583 (16)	171 (2)

Symmetry codes: (i) ; (ii) .

Table 3

Hydrogen-bond geometry (Å, °) for 3

Cg is the centroid of the C1–C6 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯N12	0.92 (3)	1.81 (3)	2.6518 (19)	152 (2)
O13—H13⋯O41i	0.91 (3)	1.89 (3)	2.7829 (18)	169 (3)
C141—H14B⋯O2ii	0.98	2.62	3.412 (2)	138
C3—H3⋯O2ii	0.95	2.70	3.570 (2)	154
C11—H11⋯Cg iii	0.95	2.89	3.4524 (6)	128

Symmetry codes: (i) ; (ii) ; (iii) .

Supra­molecular features

Hydrogen Bonding

In the crystal of 1, mol­ecules are linked by O13—H13 ⋯O2 hydrogen bonds into inversion-related (14) dimers (Table 1 ▸). As stated above, such dimers are the most frequently found arrangement for salicyldoxime derivatives. These (14), or (10) (via the intra­molecular hydrogen bond) dimers are linked into two-mol­ecule-wide chains, propagating in the a-axis direction by pairs of O13—H13⋯O13 hydrogen bonds, thereby creating (4) rings, as shown in Fig. 4 ▸. The H13⋯O13 lengths in the O13—H13⋯O13ii hydrogen bond are rather long [2.611 (16) Å] with a small angle of 100.8 (12)°. However, such data fits well with published findings for H2O2 rings: a recent CSD (Groom et al., 2016 ▸) search revealed more than 500 entries for non-solvated structures having centrosymmetric H2O2 rings with H—O—H angles of 120° or less and H⋯O distances up to the sum of the van der Waals contact radii, 2.72 Å, of oxygen and hydrogen atoms. The two-mol­ecule-wide chains are further linked into a three-dimensional arrangement by C3—H3⋯Cg iii and C11—H11⋯ Cg iv inter­actions (Table 1 ▸). No π–π inter­actions can be identified.

Figure 4

Part of a two-mol­ecule-wide chain in 1 (symmetry codes as in Table 1 ▸).

Compound 2 with two hydroxyl groups, as well as the oxime moiety, produces a much more complex classical hydrogen-bonding arrangement than the one found for compound 1. The bonding arrangement in 2 can be readily considered to be composed of two elements: a C9 chain, generated from O13—H13(oxime)⋯O4(4-hy­droxy)ii hydrogen bonds, propagating in the direction of the b axis, see Fig. 5 ▸, and secondly a zigzag C6 spiral chain formed from O4—H4⋯O2i hydrogen bonds, see Fig. 6 ▸. The C6 and C9 chains combine to form a bimol­ecular sheet running parallel to the b axis which lies between 0–½ c and ½–1 c. These sheets are further linked by moderately strong π–π stacking inter­actions, involving all the phenyl rings in the sheet: the Cg⋯Cg separation is 3.7242 (13) Å with a phenyl ring slippage of 1.586 Å. The lack of an (14) dimer in 2 is apparent and results from the preferential inter­action of the oxime group with the 4-hydroxyl group rather than with the 2-hy­droxy group.

Figure 5

Compound 2. Part of a C9 chain, propagating in the b-axis direction, formed by O13—H13⋯O4 hydrogen bonds.

Figure 6

Compound 2, part of a spiral C6 chain formed from O4—H4⋯O2 hydrogen bonds

In compound 3, C9 chains are generated from O13—H13⋯O41(meth­oxy)i hydrogen bonds, which propagate in the direction of the b axis, see Fig. 7 ▸. This chain is similar to that found in compound 2, but involving the meth­oxy oxygen atom O41 involved instead of the hy­droxy oxygen O4. Inter­estingly, the parameters of the two hydrogen bonds in the chains of compound 2 and 3 are very similar. The chains in compound 3 are linked into a two-dimensional array by C11—H11⋯Cg (Table 3 ▸) and π–π inter­actions. The centroid–centroid separation in the π–π inter­action is 3.7926 (12) Å with a phenyl ring slippage of 1.571 Å – again similar parameters are found in the inter­actions of compounds 2 and 3. The lack of an (14) dimer results from the preferential inter­action of the oxime group with the 4-meth­oxy group rather than with the 2-hy­droxy group. The C141—H14B⋯O2ii and C3—H3⋯O2iii hydrogen bonds link the molecules into centrosymmetric dimers across the centre of symmetry at (½, 0, ½). The former hydrogen bond forms (14) rings, and the latter (8) rings. These link anti-parallel C9 chains, forming a corrugated ribbon which runs parallel to the a axis.

Figure 7

Compound 3, part of a C9 chain of mol­ecules formed by O13—H13⋯O41 hydrogen bonds, propagating along the a-axis direction.

Hirshfeld Surface Analyses

The Hirshfeld surfaces (Spackman & Jayatilaka, 2009 ▸) and two-dimensional fingerprint (FP) plots (Spackman & McKinnon, 2002 ▸) provide complementary information concerning the inter­molecular inter­actions discussed above. The analyses were generated using CrystalExplorer3.1 (Wolff et al., 2012 ▸). The Hirshfeld surfaces mapped over d norm for 1–3 are illustrated in Fig. 8 ▸. The intense red areas on the surfaces correspond to O⋯H close contacts. The less intense red spot on the surface of 1 relates to a O⋯O short contact. The fingerprint plots are shown in Fig. 9 ▸. The percentage contributions to the Hirshfeld surface of the various atom⋯atom contacts shown in Table 4 ▸ are derived from the fingerprint plots.

Figure 8

Views of the Hirshfeld surfaces mapped over d norm for 1–3. In each case, the red areas relate to classical hydrogen bonds.

Figure 9

The FP plots for 1, 2 and 3. The pair of southwest spikes are due to the O⋯H /H⋯O close contacts. The highest intensity of pixels in the FP plot for 2 at d e/d i = 1.8 Å includes C⋯C contacts.

Table 4

Percentages of atom–atom contacts for compounds 1–3

Compound	1	2	3
H⋯H	42.7	36.9	41.5
H⋯O/O⋯H	21.4	33.8	27.9
H⋯C/C⋯H	29.1	10.0	15.5
H⋯N/N⋯H	5.4	2.9	4.1
C⋯C	–	10.8	5.8
O⋯C/C⋯O	1.2	2.2	3.1
N⋯O/O⋯N	–	2.0	0.7
N⋯C/C⋯N	–	–	–
O⋯O	0.2	–	–

There are some differences in the percentage of close contacts listed in Table 4 ▸ between the (14) dimer formed by compound 1 and the mol­ecular chains formed by compounds 2 and 3. Thus compound 1 exhibits the highest percentage of H⋯C/ C⋯H close contacts, but no C⋯C and N⋯O/ O⋯N close contacts, unlike compounds 2 and 3, and is the only one of the three compounds to have any close O⋯O contacts, albeit a very small percentage. It has to be said that the different substituents, especially the number of hydroxyl units, and other inter­actions, such as C—H⋯π and π–π inter­actions, will have significant effects on the hydrogen-bonding.

Database survey

A survey of the Cambridge Structural Database (CSD Version 5.39, May 2018 update; Groom et al., 2016 ▸) of the hydrogen-bonding patterns of oximes confirmed the invariable occurrence for salicylaldoximes, R—CH=N—OH (where R is a 2-hy­droxy­phenyl derivative) of the formation of intra­molecular O—H⋯NO(oxime) hydrogen bonds involv­ing the ortho hydroxyl group. In addition, this hydroxyl group is also most frequently involved in inter­molecular inter­actions producing inversion-related (14) dimers (Smith et al., 2003 ▸; Wood et al., 2006 ▸, 2008b ▸). Exceptions include MXSALO [R = 2-HO-5-MeOC6H3, producing a C5 chain from O—H(oxime)⋯O(2-hydrox­yl) hydrogen bonds; Pfluger et al., 1978 ▸], YUPSOT [R = 2-HO-5-Bu-C6H3, producing a C5 chain from O—H(oxime)⋯O(2-hydrox­yl) hydrogen bonds; White et al., 2015a ▸], YUPROS [R = 2-HO-3-Me-5-(piperin-1-yl-CH2)-C6H2, producing a C9 chain from O—H(oxime)⋯N(piperin­yl) hydrogen bonds; White et al., 2015b ▸] and XUSPIL [R = 2-HO-3-(piperin-1-ylmeth­yl)-5-Bu-C6H2, producing a C9 chain from O—H(oxime)⋯N(piperin­yl) hydrogen bonds; Forgan et al., 2010 ▸].

The compounds 2-HO-3-MeOC6H3CH=N—OH (ABULIT01–07; Forgan et al., 2007 ▸; Wood et al., 2008a ▸) and 2-HO-3-EtOC6H3CH=N—OH (HAHGAA; Cai, 2011 ▸) both form (14) dimers, in contrast to the chain forming 2-HO-4-MeOC6H3CH=N—OH (this study) and 2-HO-5-MeOC6H3CH=N—OH (MXSALO; Pfluger et al., 1978 ▸) and 2-HO-5-BuOC6H3CH=N—OH (YUPSOT; White et al., 2015a ▸).

An earlier search (Low et al., 2010 ▸) indicated that the most frequently found hydrogen-bonding arrangements for oximes without a 2-hy­droxy­phenyl group are inversion-related (6) dimers and C3 chains.

Synthesis and crystallization

The title compounds were prepared from hydroxyl­amine and the corresponding benzaldehyde in methanol in the presence of potassium carbonate and were recrystallized from methanol. Compound 1, m.p. 378–379 K. Compound 2, m.p. 451–452 K. Compound 3, m.p. 410–411 K.

Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 5 ▸. All hydroxyl H atoms were refined isotropically. Those attached to C atoms were refined as riding atoms with C—H = 0.95–0.98 Å and U iso(H) = 1.2–1.5U iso(C).

Table 5

Experimental details

	1	2	3
Crystal data
Chemical formula	C8H9NO2	C7H7NO3	C8H9NO3
M r	151.16	153.14	167.16
Crystal system, space group	Monoclinic, P21/n	Monoclinic, P21/c	Monoclinic, P21/c
Temperature (K)	100	100	100
a, b, c (Å)	6.5507 (2), 7.2523 (2), 15.5478 (4)	3.7241 (1), 8.6902 (2), 20.7570 (5)	9.3591 (13), 6.2634 (7), 13.6260 (2)
β (°)	96.737 (3)	92.501 (2)	108.636 (16)
V (Å3)	733.54 (4)	671.12 (3)	756.87 (15)
Z	4	4	4
Radiation type	Mo Kα	Mo Kα	Mo Kα
μ (mm−1)	0.10	0.12	0.11
Crystal size (mm)	0.25 × 0.15 × 0.02	0.20 × 0.10 × 0.05	0.15 × 0.05 × 0.01
Data collection
Diffractometer	Rigaku FRE+ AFC12 with HyPix 6000 detector	Rigaku FRE+ AFC12 with HyPix 6000 detector	Rigaku FRE+ AFC12 with HyPix 6000 detector
Absorption correction	Multi-scan (CrysAlis PRO ; Rigaku OD, 2017 ▸)	Multi-scan (CrysAlis PRO ; Rigaku OD, 2017 ▸)	Multi-scan (CrysAlis PRO; Rigaku OD, 2017 ▸)
T min, T max	0.742, 1.000	0.654, 1.000	0.305, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	16323, 1696, 1560	29482, 1537, 1482	5525, 1686, 1323
R int	0.024	0.039	0.060
(sin θ/λ)max (Å−1)	0.649	0.649	0.648
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.032, 0.100, 1.08	0.040, 0.092, 0.86	0.049, 0.158, 1.01
No. of reflections	1696	1537	1686
No. of parameters	109	113	118
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement	H atoms treated by a mixture of independent and constrained refinement	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.33, −0.20	0.38, −0.21	0.26, −0.29

Computer programs: CrysAlis PRO (Rigaku OD, 2017 ▸), OSCAIL (McArdle et al., 2004 ▸), SHELXT (Sheldrick, 2015a ▸), ShelXle (Hübschle et al., 2011 ▸), SHELXL2017/1 (Sheldrick, 2015b ▸), Mercury (Macrae et al., 2006 ▸) and PLATON (Spek, 2009 ▸).

Crystal structure: contains datablock(s) 1, 2, 3, global. DOI: 10.1107/S2056989018013361/qm2128sup1.cif

Structure factors: contains datablock(s) 1. DOI: 10.1107/S2056989018013361/qm21281sup2.hkl

Structure factors: contains datablock(s) 2. DOI: 10.1107/S2056989018013361/qm21282sup3.hkl

Structure factors: contains datablock(s) 3. DOI: 10.1107/S2056989018013361/qm21283sup4.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989018013361/qm21281sup5.cml

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989018013361/qm21282sup6.cml

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989018013361/qm21283sup7.cml

CCDC references: 1868656, 1868655, 1868654

Additional supporting information: crystallographic information; 3D view; checkCIF report

C8H9NO2	F(000) = 320
Mr = 151.16	Dx = 1.369 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71075 Å
a = 6.5507 (2) Å	Cell parameters from 8222 reflections
b = 7.2523 (2) Å	θ = 3.1–31.9°
c = 15.5478 (4) Å	µ = 0.10 mm−1
β = 96.737 (3)°	T = 100 K
V = 733.54 (4) Å3	Plate, brown
Z = 4	0.25 × 0.15 × 0.02 mm

Rigaku FRE+ AFC12 with HyPix 6000 detector diffractometer	1696 independent reflections
Radiation source: Rotating Anode, Rigaku FRE+	1560 reflections with I > 2σ(I)
Confocal mirrors, VHF Varimax monochromator	Rint = 0.024
Detector resolution: 10 pixels mm-1	θmax = 27.5°, θmin = 2.6°
profile data from ω–scans	h = −8→8
Absorption correction: multi-scan (CrysAlisPro ; Rigaku OD, 2017)	k = −9→9
Tmin = 0.742, Tmax = 1.000	l = −20→20
16323 measured reflections

Refinement on F2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.032	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.100	w = 1/[σ2(Fo2) + (0.0569P)2 + 0.1857P] where P = (Fo2 + 2Fc2)/3
S = 1.08	(Δ/σ)max < 0.001
1696 reflections	Δρmax = 0.33 e Å−3
109 parameters	Δρmin = −0.20 e Å−3

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.

	x	y	z	Uiso*/Ueq
O2	0.62147 (10)	0.55213 (9)	0.38936 (4)	0.01715 (19)
H2	0.520 (3)	0.516 (2)	0.4176 (11)	0.046 (4)*
O13	0.11027 (10)	0.35295 (10)	0.46255 (4)	0.01893 (19)
H13	0.155 (2)	0.389 (2)	0.5139 (11)	0.041 (4)*
N12	0.27030 (11)	0.40720 (11)	0.41612 (5)	0.01501 (19)
C1	0.38496 (13)	0.41353 (12)	0.27677 (5)	0.0129 (2)
C2	0.57244 (13)	0.50209 (12)	0.30486 (5)	0.0131 (2)
C3	0.71163 (13)	0.54354 (12)	0.24671 (6)	0.0139 (2)
H3	0.837332	0.603208	0.266799	0.017*
C4	0.66904 (13)	0.49864 (12)	0.15934 (6)	0.0137 (2)
C5	0.48296 (14)	0.41041 (12)	0.13081 (6)	0.0144 (2)
H5	0.451750	0.379046	0.071398	0.017*
C6	0.34460 (13)	0.36875 (12)	0.18861 (6)	0.0139 (2)
H6	0.219471	0.308503	0.168196	0.017*
C11	0.23470 (13)	0.36707 (12)	0.33550 (6)	0.0139 (2)
H11	0.110265	0.306989	0.313953	0.017*
C41	0.81701 (14)	0.54974 (13)	0.09625 (6)	0.0173 (2)
H41A	0.814596	0.454650	0.051360	0.026*
H41B	0.956069	0.559362	0.126945	0.026*
H41C	0.776779	0.668498	0.069346	0.026*

	U11	U22	U33	U12	U13	U23
O2	0.0175 (3)	0.0221 (4)	0.0115 (3)	−0.0050 (3)	0.0003 (2)	−0.0029 (2)
O13	0.0156 (3)	0.0260 (4)	0.0162 (3)	−0.0046 (3)	0.0059 (3)	−0.0030 (3)
N12	0.0137 (4)	0.0158 (4)	0.0162 (4)	−0.0005 (3)	0.0048 (3)	0.0001 (3)
C1	0.0133 (4)	0.0110 (4)	0.0141 (4)	0.0013 (3)	0.0009 (3)	0.0004 (3)
C2	0.0159 (4)	0.0114 (4)	0.0115 (4)	0.0016 (3)	−0.0009 (3)	−0.0006 (3)
C3	0.0135 (4)	0.0124 (4)	0.0153 (4)	−0.0004 (3)	−0.0001 (3)	0.0000 (3)
C4	0.0152 (4)	0.0112 (4)	0.0147 (4)	0.0020 (3)	0.0016 (3)	0.0009 (3)
C5	0.0166 (4)	0.0137 (4)	0.0124 (4)	0.0015 (3)	−0.0009 (3)	−0.0008 (3)
C6	0.0133 (4)	0.0122 (4)	0.0153 (4)	0.0005 (3)	−0.0016 (3)	−0.0009 (3)
C11	0.0132 (4)	0.0118 (4)	0.0164 (4)	0.0007 (3)	0.0007 (3)	−0.0005 (3)
C41	0.0177 (4)	0.0192 (4)	0.0153 (4)	−0.0016 (3)	0.0029 (3)	0.0000 (3)

O2—C2	1.3645 (10)	C3—H3	0.9500
O2—H2	0.879 (18)	C4—C5	1.4018 (13)
O13—N12	1.3973 (9)	C4—C41	1.5041 (12)
O13—H13	0.857 (17)	C5—C6	1.3826 (12)
N12—C11	1.2812 (11)	C5—H5	0.9500
C1—C6	1.4033 (12)	C6—H6	0.9500
C1—C2	1.4091 (12)	C11—H11	0.9500
C1—C11	1.4584 (12)	C41—H41A	0.9800
C2—C3	1.3902 (12)	C41—H41B	0.9800
C3—C4	1.3928 (12)	C41—H41C	0.9800
C2—O2—H2	107.2 (11)	C6—C5—C4	120.40 (8)
N12—O13—H13	101.6 (11)	C6—C5—H5	119.8
C11—N12—O13	112.33 (7)	C4—C5—H5	119.8
C6—C1—C2	117.75 (8)	C5—C6—C1	121.44 (8)
C6—C1—C11	119.63 (8)	C5—C6—H6	119.3
C2—C1—C11	122.61 (8)	C1—C6—H6	119.3
O2—C2—C3	118.06 (8)	N12—C11—C1	120.08 (8)
O2—C2—C1	121.18 (8)	N12—C11—H11	120.0
C3—C2—C1	120.75 (8)	C1—C11—H11	120.0
C2—C3—C4	120.80 (8)	C4—C41—H41A	109.5
C2—C3—H3	119.6	C4—C41—H41B	109.5
C4—C3—H3	119.6	H41A—C41—H41B	109.5
C3—C4—C5	118.86 (8)	C4—C41—H41C	109.5
C3—C4—C41	120.51 (8)	H41A—C41—H41C	109.5
C5—C4—C41	120.60 (8)	H41B—C41—H41C	109.5
C6—C1—C2—O2	179.14 (7)	C3—C4—C5—C6	−0.06 (13)
C11—C1—C2—O2	−1.14 (14)	C41—C4—C5—C6	−178.02 (8)
C6—C1—C2—C3	0.13 (13)	C4—C5—C6—C1	0.24 (14)
C11—C1—C2—C3	179.86 (8)	C2—C1—C6—C5	−0.28 (13)
O2—C2—C3—C4	−178.99 (7)	C11—C1—C6—C5	179.99 (7)
C1—C2—C3—C4	0.04 (14)	O13—N12—C11—C1	179.95 (7)
C2—C3—C4—C5	−0.08 (13)	C6—C1—C11—N12	179.91 (8)
C2—C3—C4—C41	177.88 (7)	C2—C1—C11—N12	0.19 (14)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···N12	0.879 (18)	1.814 (18)	2.6066 (10)	149.0 (15)
O13—H13···O2i	0.857 (17)	2.019 (17)	2.8132 (9)	153.7 (15)
O13—H13···O13ii	0.857 (17)	2.611 (16)	2.8961 (14)	100.8 (12)
C3—H3···Cgiii	0.95	2.71	3.4577 (9)	136
C11—H11···Cgiv	0.95	2.73	3.4910 (9)	138

C7H7NO3	F(000) = 320
Mr = 153.14	Dx = 1.516 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71075 Å
a = 3.7241 (1) Å	Cell parameters from 13388 reflections
b = 8.6902 (2) Å	θ = 1.9–32.1°
c = 20.7570 (5) Å	µ = 0.12 mm−1
β = 92.501 (2)°	T = 100 K
V = 671.12 (3) Å3	Block, colourless
Z = 4	0.20 × 0.10 × 0.05 mm

Rigaku FRE+ AFC12 with HyPix 6000 detector diffractometer	1537 independent reflections
Radiation source: Rotating Anode, Rigaku FRE+	1482 reflections with I > 2σ(I)
Confocal mirrors, VHF Varimax monochromator	Rint = 0.039
Detector resolution: 10 pixels mm-1	θmax = 27.5°, θmin = 2.0°
profile data from ω–scans	h = −4→4
Absorption correction: multi-scan (CrysAlisPro ; Rigaku OD, 2017)	k = −11→11
Tmin = 0.654, Tmax = 1.000	l = −26→26
29482 measured reflections

Refinement on F2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.040	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.092	w = 1/[σ2(Fo2) + (0.0229P)2 + 1.3357P] where P = (Fo2 + 2Fc2)/3
S = 0.86	(Δ/σ)max < 0.001
1537 reflections	Δρmax = 0.38 e Å−3
113 parameters	Δρmin = −0.21 e Å−3

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. Refined as a 2-component twin.

	x	y	z	Uiso*/Ueq
O2	0.6604 (3)	0.13314 (13)	0.28983 (5)	0.0175 (3)
H2	0.568 (7)	0.056 (3)	0.3130 (12)	0.045 (7)*
O4	1.0469 (3)	0.64910 (12)	0.32704 (5)	0.0167 (3)
H4	1.132 (6)	0.639 (3)	0.2893 (11)	0.031 (6)*
O13	0.2536 (3)	−0.13686 (13)	0.41952 (6)	0.0213 (3)
H13	0.208 (7)	−0.200 (3)	0.3880 (12)	0.043 (7)*
N12	0.3984 (4)	−0.01346 (15)	0.38573 (6)	0.0161 (3)
C1	0.6052 (4)	0.24418 (16)	0.39524 (7)	0.0125 (3)
C2	0.7061 (4)	0.25485 (16)	0.33098 (7)	0.0129 (3)
C3	0.8530 (4)	0.38889 (17)	0.30720 (7)	0.0133 (3)
H3	0.9193	0.3946	0.2636	0.016*
C4	0.9020 (4)	0.51454 (17)	0.34786 (7)	0.0133 (3)
C5	0.8047 (4)	0.50773 (17)	0.41191 (7)	0.0148 (3)
H5	0.8379	0.5943	0.4395	0.018*
C6	0.6596 (4)	0.37332 (17)	0.43460 (7)	0.0141 (3)
H6	0.5947	0.3683	0.4783	0.017*
C11	0.4474 (4)	0.10553 (17)	0.42134 (7)	0.0144 (3)
H11	0.3805	0.1034	0.4650	0.017*

	U11	U22	U33	U12	U13	U23
O2	0.0273 (6)	0.0106 (5)	0.0150 (5)	−0.0041 (5)	0.0047 (4)	−0.0036 (4)
O4	0.0249 (6)	0.0096 (5)	0.0161 (5)	−0.0052 (4)	0.0051 (4)	0.0002 (4)
O13	0.0335 (7)	0.0110 (5)	0.0194 (6)	−0.0095 (5)	0.0025 (5)	0.0019 (4)
N12	0.0189 (6)	0.0103 (6)	0.0191 (6)	−0.0029 (5)	0.0010 (5)	0.0030 (5)
C1	0.0127 (7)	0.0096 (6)	0.0151 (7)	0.0003 (5)	0.0005 (5)	0.0003 (5)
C2	0.0142 (7)	0.0101 (6)	0.0143 (7)	0.0008 (5)	−0.0003 (5)	−0.0023 (5)
C3	0.0149 (7)	0.0123 (7)	0.0126 (6)	0.0003 (6)	0.0020 (5)	0.0000 (5)
C4	0.0135 (7)	0.0087 (6)	0.0176 (7)	−0.0005 (5)	0.0009 (5)	0.0020 (5)
C5	0.0180 (7)	0.0106 (7)	0.0158 (7)	−0.0010 (6)	0.0015 (6)	−0.0027 (5)
C6	0.0158 (7)	0.0132 (7)	0.0135 (7)	−0.0005 (6)	0.0021 (5)	−0.0010 (5)
C11	0.0158 (7)	0.0117 (7)	0.0156 (7)	−0.0003 (6)	0.0003 (5)	0.0019 (5)

O2—C2	1.3655 (17)	C1—C11	1.456 (2)
O2—H2	0.91 (3)	C2—C3	1.387 (2)
O4—C4	1.3660 (17)	C3—C4	1.387 (2)
O4—H4	0.86 (2)	C3—H3	0.9500
O13—N12	1.4020 (16)	C4—C5	1.394 (2)
O13—H13	0.86 (3)	C5—C6	1.378 (2)
N12—C11	1.280 (2)	C5—H5	0.9500
C1—C6	1.398 (2)	C6—H6	0.9500
C1—C2	1.405 (2)	C11—H11	0.9500
C2—O2—H2	106.5 (16)	O4—C4—C3	121.64 (13)
C4—O4—H4	111.3 (15)	O4—C4—C5	117.43 (13)
N12—O13—H13	99.9 (16)	C3—C4—C5	120.93 (14)
C11—N12—O13	112.18 (13)	C6—C5—C4	118.93 (14)
C6—C1—C2	117.65 (13)	C6—C5—H5	120.5
C6—C1—C11	119.85 (13)	C4—C5—H5	120.5
C2—C1—C11	122.50 (13)	C5—C6—C1	121.98 (14)
O2—C2—C3	117.93 (13)	C5—C6—H6	119.0
O2—C2—C1	120.77 (13)	C1—C6—H6	119.0
C3—C2—C1	121.30 (13)	N12—C11—C1	120.25 (14)
C2—C3—C4	119.22 (13)	N12—C11—H11	119.9
C2—C3—H3	120.4	C1—C11—H11	119.9
C4—C3—H3	120.4
C6—C1—C2—O2	−179.97 (14)	O4—C4—C5—C6	−179.63 (14)
C11—C1—C2—O2	−0.2 (2)	C3—C4—C5—C6	0.3 (2)
C6—C1—C2—C3	−0.3 (2)	C4—C5—C6—C1	−0.4 (2)
C11—C1—C2—C3	179.41 (14)	C2—C1—C6—C5	0.4 (2)
O2—C2—C3—C4	179.88 (13)	C11—C1—C6—C5	−179.33 (14)
C1—C2—C3—C4	0.2 (2)	O13—N12—C11—C1	178.31 (12)
C2—C3—C4—O4	179.71 (14)	C6—C1—C11—N12	−179.63 (14)
C2—C3—C4—C5	−0.2 (2)	C2—C1—C11—N12	0.6 (2)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···N12	0.91 (3)	1.77 (3)	2.5899 (17)	150 (2)
O4—H4···O2i	0.86 (2)	1.85 (2)	2.7062 (16)	174 (2)
O13—H13···O4ii	0.86 (3)	1.90 (3)	2.7583 (16)	171 (2)

C8H9NO3	F(000) = 352
Mr = 167.16	Dx = 1.467 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71075 Å
a = 9.3591 (13) Å	Cell parameters from 1379 reflections
b = 6.2634 (7) Å	θ = 3.3–30.2°
c = 13.6260 (2) Å	µ = 0.11 mm−1
β = 108.636 (16)°	T = 100 K
V = 756.87 (15) Å3	Plate, colourless
Z = 4	0.15 × 0.05 × 0.01 mm

Rigaku FRE+ AFC12 with HyPix 6000 detector diffractometer	1686 independent reflections
Radiation source: Rotating Anode, Rigaku FRE+	1323 reflections with I > 2σ(I)
Confocal mirrors, VHF Varimax monochromator	Rint = 0.060
Detector resolution: 10 pixels mm-1	θmax = 27.4°, θmin = 2.3°
profile data from ω–scans	h = −11→12
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2017)	k = −7→7
Tmin = 0.305, Tmax = 1.000	l = −17→17
5525 measured reflections

Refinement on F2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.049	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.158	w = 1/[σ2(Fo2) + (0.1063P)2] where P = (Fo2 + 2Fc2)/3
S = 1.00	(Δ/σ)max < 0.001
1686 reflections	Δρmax = 0.26 e Å−3
118 parameters	Δρmin = −0.29 e Å−3

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.

	x	y	z	Uiso*/Ueq
O2	0.63191 (14)	0.1847 (2)	0.42822 (9)	0.0193 (3)
H2	0.711 (3)	0.265 (5)	0.423 (2)	0.049 (7)*
O13	0.91351 (14)	0.6293 (2)	0.38674 (10)	0.0228 (4)
H13	0.981 (3)	0.524 (5)	0.388 (2)	0.062 (9)*
O41	0.10398 (13)	0.30632 (19)	0.36291 (8)	0.0182 (3)
N12	0.78766 (16)	0.5076 (2)	0.38782 (11)	0.0175 (4)
C1	0.52304 (18)	0.5260 (3)	0.36005 (11)	0.0145 (4)
C2	0.51014 (18)	0.3173 (3)	0.39480 (11)	0.0147 (4)
C3	0.37212 (18)	0.2374 (3)	0.39667 (12)	0.0158 (4)
H3	0.365066	0.097118	0.421199	0.019*
C4	0.24440 (19)	0.3667 (3)	0.36197 (12)	0.0150 (4)
C5	0.25337 (19)	0.5722 (3)	0.32479 (12)	0.0172 (4)
H5	0.165354	0.657670	0.299366	0.021*
C6	0.39104 (19)	0.6495 (3)	0.32543 (12)	0.0158 (4)
H6	0.397195	0.790761	0.301740	0.019*
C11	0.66646 (18)	0.6195 (3)	0.36181 (12)	0.0157 (4)
H11	0.670249	0.765245	0.343458	0.019*
C141	0.0866 (2)	0.0952 (3)	0.39792 (14)	0.0220 (4)
H14A	−0.018185	0.074061	0.395637	0.033*
H14B	0.153667	0.076825	0.469161	0.033*
H14C	0.112340	−0.009659	0.352899	0.033*

	U11	U22	U33	U12	U13	U23
O2	0.0191 (7)	0.0148 (6)	0.0240 (7)	0.0044 (5)	0.0068 (5)	0.0056 (5)
O13	0.0187 (6)	0.0164 (7)	0.0360 (8)	−0.0006 (5)	0.0127 (5)	0.0018 (5)
O41	0.0181 (6)	0.0152 (7)	0.0220 (6)	0.0002 (5)	0.0075 (5)	0.0021 (4)
N12	0.0179 (7)	0.0163 (8)	0.0200 (7)	−0.0027 (5)	0.0083 (6)	−0.0003 (5)
C1	0.0200 (8)	0.0122 (8)	0.0122 (8)	−0.0001 (6)	0.0062 (6)	−0.0011 (6)
C2	0.0175 (8)	0.0147 (8)	0.0121 (7)	0.0024 (6)	0.0051 (6)	−0.0005 (6)
C3	0.0216 (9)	0.0118 (8)	0.0149 (8)	0.0013 (6)	0.0073 (6)	0.0007 (6)
C4	0.0180 (8)	0.0155 (9)	0.0119 (7)	−0.0001 (6)	0.0054 (6)	−0.0024 (6)
C5	0.0204 (8)	0.0150 (8)	0.0160 (8)	0.0045 (6)	0.0055 (6)	0.0006 (6)
C6	0.0235 (9)	0.0106 (8)	0.0139 (8)	0.0017 (6)	0.0068 (6)	0.0008 (6)
C11	0.0204 (9)	0.0131 (8)	0.0143 (8)	0.0004 (6)	0.0065 (6)	−0.0004 (5)
C141	0.0225 (9)	0.0144 (9)	0.0290 (9)	−0.0018 (7)	0.0082 (7)	0.0031 (7)

O2—C2	1.365 (2)	C3—C4	1.395 (2)
O2—H2	0.92 (3)	C3—H3	0.9500
O13—N12	1.4067 (18)	C4—C5	1.396 (2)
O13—H13	0.91 (3)	C5—C6	1.374 (2)
O41—C4	1.371 (2)	C5—H5	0.9500
O41—C141	1.432 (2)	C6—H6	0.9500
N12—C11	1.283 (2)	C11—H11	0.9500
C1—C2	1.409 (2)	C141—H14A	0.9800
C1—C6	1.405 (2)	C141—H14B	0.9800
C1—C11	1.458 (2)	C141—H14C	0.9800
C2—C3	1.393 (2)
C2—O2—H2	104.4 (17)	C6—C5—C4	119.18 (15)
N12—O13—H13	100.6 (19)	C6—C5—H5	120.4
C4—O41—C141	117.95 (13)	C4—C5—H5	120.4
C11—N12—O13	111.75 (14)	C5—C6—C1	122.04 (15)
C2—C1—C6	117.58 (15)	C5—C6—H6	119.0
C2—C1—C11	123.02 (15)	C1—C6—H6	119.0
C6—C1—C11	119.37 (15)	N12—C11—C1	120.87 (16)
O2—C2—C3	117.11 (15)	N12—C11—H11	119.6
O2—C2—C1	121.63 (15)	C1—C11—H11	119.6
C3—C2—C1	121.26 (15)	O41—C141—H14A	109.5
C4—C3—C2	118.99 (15)	O41—C141—H14B	109.5
C4—C3—H3	120.5	H14A—C141—H14B	109.5
C2—C3—H3	120.5	O41—C141—H14C	109.5
O41—C4—C3	123.83 (15)	H14A—C141—H14C	109.5
O41—C4—C5	115.24 (14)	H14B—C141—H14C	109.5
C3—C4—C5	120.92 (16)
C6—C1—C2—O2	178.92 (13)	C2—C3—C4—C5	0.7 (2)
C11—C1—C2—O2	−3.1 (2)	O41—C4—C5—C6	177.11 (13)
C6—C1—C2—C3	−1.2 (2)	C3—C4—C5—C6	−1.9 (2)
C11—C1—C2—C3	176.75 (14)	C4—C5—C6—C1	1.6 (2)
O2—C2—C3—C4	−179.21 (13)	C2—C1—C6—C5	−0.1 (2)
C1—C2—C3—C4	0.9 (2)	C11—C1—C6—C5	−178.10 (14)
C141—O41—C4—C3	−2.5 (2)	O13—N12—C11—C1	−178.61 (13)
C141—O41—C4—C5	178.56 (14)	C2—C1—C11—N12	5.8 (2)
C2—C3—C4—O41	−178.25 (14)	C6—C1—C11—N12	−176.33 (14)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···N12	0.92 (3)	1.81 (3)	2.6518 (19)	152 (2)
O13—H13···O41i	0.91 (3)	1.89 (3)	2.7829 (18)	169 (3)
C141—H14B···O2ii	0.98	2.62	3.412 (2)	138
C3—H3···O2ii	0.95	2.70	3.570 (2)	154
C11—H11···Cgiii	0.95	2.89	3.4524 (6)	128