Crystal structure and Hirshfeld surface analysis of lapachol acetate 80 years after its first synthesis

A modified synthesis procedure allowed lapachol acetate (acetic acid 3-(3-methyl-but-2-en­yl)-1,4-dioxo-1,4-di­hydro- naphthalen-2-yl ester) to be obtained in high yield and its crystal structure is reported for the first time 80 years after its first synthesis. The lapachol acetate mol­ecular conformation is very similar to that of reported lapachol mol­ecules and other derivatives. The monoclinic P2₁/n crystal structure packs through weak inter­molecular π–π and C—H...O inter­actions as described by Hirshfeld surface analysis.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.003 Å
• Disorder in main residue
• R factor = 0.048
• wR factor = 0.136
• Data-to-parameter ratio = 15.5

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT242_ALERT_2_C Low    'MainMol' Ueq as Compared to Neighbors of        C16 Check

Author Response: C16 is the center of the acetato group, bonded to O3 and C17, both therminal atoms with more vibrational freedom and larger ADPs, this artificially makes C16 appear as having lower Ueq than normal but this is not the case.

PLAT906_ALERT_3_C Large K Value in the Analysis of Variance ......      2.289 Check

Author Response: It is well known that background can be overestimated in 2D CMOS detectors and weak reflections can be underestimated, the observed large K value only affects 10% of reflections with I lower than 0.4%.

PLAT911_ALERT_3_C Missing FCF Refl Between Thmin & STh/L=    0.600         36 Report

Author Response: Due to geometrical restrictions of the goniometer it was impossible to collect all reflections below 0.600.

Alert level G
PLAT171_ALERT_4_G The CIF-Embedded .res File Contains EADP Records          1 Report
PLAT301_ALERT_3_G Main Residue  Disorder ..............(Resd  1  )         5% Note
PLAT333_ALERT_2_G Large Aver C6-Ring C-C Dist C1       -C9       .       1.44 Ang.
PLAT335_ALERT_2_G Check Large C6 Ring C-C Range C1       -C9             0.15 Ang.
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600        129 Note
PLAT978_ALERT_2_G Number C-C Bonds with Positive Residual Density.          3 Info

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   3 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   6 ALERT level G = General information/check it is not something unexpected

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   4 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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Computing details

Data collection: APEX2 (Bruker, 2014); cell refinement: SAINT (Bruker, 2014); data reduction: SAINT (Bruker, 2014); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: publCIF (Westrip, 2010).

3-(3-Methylbut-2-enyl)-1,4-dioxonaphthalen-2-yl acetate

Crystal data

C17H16O4	Dx = 1.292 Mg m^−3
Mr = 284.30	Melting point: 352(1) K
Monoclinic, P21/n	Cu Kα radiation, λ = 1.54178 Å
a = 12.0914 (8) Å	Cell parameters from 7958 reflections
b = 9.4741 (6) Å	θ = 4.9–75.7°
c = 12.7761 (9) Å	µ = 0.75 mm^−1
β = 92.943 (4)°	T = 296 K
V = 1461.64 (17) Å^3	Block, yellow
Z = 4	0.26 × 0.22 × 0.18 mm
F(000) = 600

Data collection

Bruker D8 Venture/Photon 100 CMOS diffractometer	2996 independent reflections
Radiation source: Cu Incoatec microsource	1972 reflections with I > 2σ(I)
Detector resolution: 10.4167 pixels mm^-1	Rint = 0.038
\j and ω scans	θmax = 79.2°, θmin = 4.9°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −13→15
Tmin = 0.654, Tmax = 0.754	k = −11→9
7496 measured reflections	l = −16→15

Refinement

Refinement on F^2	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.048	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.136	H-atom parameters constrained
S = 1.03	w = 1/[σ^2(Fo^2) + (0.053P)^2 + 0.3463P] where P = (Fo^2 + 2Fc^2)/3
2996 reflections	(Δ/σ)max < 0.001
193 parameters	Δρmax = 0.17 e Å^−3
0 restraints	Δρmin = −0.16 e Å^−3

Special details

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.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.22182 (14)	0.34297 (18)	0.34233 (12)	0.0686 (5)
C1	0.25877 (15)	0.3726 (2)	0.42998 (15)	0.0468 (5)
O2	0.17186 (11)	0.16221 (16)	0.49500 (11)	0.0540 (4)
C2	0.24117 (15)	0.2761 (2)	0.51890 (15)	0.0441 (5)
O3	0.30987 (14)	0.05735 (18)	0.41410 (15)	0.0756 (5)
C3	0.28099 (15)	0.2973 (2)	0.61720 (15)	0.0443 (5)
O4	0.39859 (12)	0.43627 (17)	0.72673 (11)	0.0586 (4)
C4	0.35332 (15)	0.4218 (2)	0.64003 (14)	0.0440 (5)
C5	0.42753 (17)	0.6488 (2)	0.57604 (17)	0.0529 (5)
H5	0.460252	0.663841	0.642578	0.063*
C6	0.43917 (18)	0.7485 (3)	0.49821 (19)	0.0615 (6)
H6	0.479948	0.830043	0.512619	0.074*
C7	0.39054 (19)	0.7275 (3)	0.39920 (19)	0.0612 (6)
H7	0.397581	0.795506	0.347504	0.073*
C8	0.33163 (17)	0.6057 (3)	0.37709 (17)	0.0547 (5)
H8	0.299507	0.591249	0.310242	0.066*
C9	0.32006 (15)	0.5041 (2)	0.45465 (15)	0.0444 (5)
C10	0.36737 (15)	0.5268 (2)	0.55524 (15)	0.0426 (4)
C11	0.26046 (18)	0.1969 (2)	0.70541 (16)	0.0533 (5)
H11A	0.260239	0.249275	0.770631	0.064*
H11B	0.188017	0.154157	0.693426	0.064*
C12	0.34630 (17)	0.0828 (2)	0.71541 (16)	0.0505 (5)
H12	0.350981	0.023269	0.657923	0.061*
C13	0.41622 (17)	0.0566 (2)	0.79619 (16)	0.0510 (5)
C14	0.4219 (2)	0.1431 (3)	0.89505 (18)	0.0719 (7)
H14A	0.412225	0.082669	0.954178	0.108*
H14B	0.364369	0.213071	0.891358	0.108*
H14C	0.492685	0.188880	0.902682	0.108*
C15	0.4952 (2)	−0.0652 (3)	0.7946 (2)	0.0684 (7)
H15A	0.569682	−0.031304	0.805937	0.103*
H15B	0.487694	−0.111606	0.727755	0.103*
H15C	0.478890	−0.130827	0.848916	0.103*
C16	0.2148 (2)	0.0591 (2)	0.43364 (17)	0.0557 (5)
C17	0.1276 (2)	−0.0443 (3)	0.3994 (2)	0.0785 (8)	0.79 (3)
H17A	0.072901	0.001798	0.354279	0.118*	0.79 (3)
H17B	0.093164	−0.081079	0.459726	0.118*	0.79 (3)
H17C	0.160520	−0.120203	0.362194	0.118*	0.79 (3)
C17'	0.1276 (2)	−0.0443 (3)	0.3994 (2)	0.0785 (8)	0.21 (3)
H17D	0.058095	−0.016088	0.425921	0.118*	0.21 (3)
H17E	0.147328	−0.136138	0.426025	0.118*	0.21 (3)
H17F	0.121161	−0.047259	0.324252	0.118*	0.21 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0903 (12)	0.0652 (12)	0.0484 (8)	−0.0047 (9)	−0.0162 (8)	0.0054 (8)
C1	0.0471 (10)	0.0480 (12)	0.0449 (11)	0.0085 (9)	−0.0009 (8)	0.0029 (9)
O2	0.0536 (8)	0.0488 (9)	0.0596 (8)	−0.0054 (7)	0.0025 (7)	−0.0014 (7)
C2	0.0430 (9)	0.0407 (11)	0.0486 (10)	0.0036 (9)	0.0025 (8)	0.0002 (9)
O3	0.0664 (10)	0.0607 (12)	0.1004 (13)	0.0026 (9)	0.0100 (9)	−0.0191 (10)
C3	0.0449 (10)	0.0430 (12)	0.0456 (10)	0.0058 (9)	0.0060 (8)	0.0037 (9)
O4	0.0653 (9)	0.0646 (11)	0.0452 (8)	0.0030 (8)	−0.0055 (7)	−0.0027 (7)
C4	0.0431 (10)	0.0448 (12)	0.0443 (10)	0.0105 (9)	0.0051 (8)	−0.0028 (9)
C5	0.0557 (12)	0.0456 (13)	0.0581 (12)	0.0034 (10)	0.0095 (10)	−0.0063 (11)
C6	0.0621 (13)	0.0424 (14)	0.0813 (16)	−0.0016 (11)	0.0171 (12)	−0.0029 (12)
C7	0.0673 (14)	0.0464 (14)	0.0715 (15)	0.0066 (11)	0.0198 (12)	0.0138 (12)
C8	0.0571 (12)	0.0534 (14)	0.0539 (12)	0.0109 (11)	0.0061 (9)	0.0098 (11)
C9	0.0457 (10)	0.0428 (12)	0.0452 (10)	0.0088 (9)	0.0065 (8)	0.0049 (9)
C10	0.0431 (9)	0.0373 (11)	0.0479 (10)	0.0086 (8)	0.0078 (8)	−0.0009 (9)
C11	0.0566 (12)	0.0559 (14)	0.0479 (11)	−0.0022 (10)	0.0067 (9)	0.0092 (10)
C12	0.0625 (12)	0.0431 (13)	0.0458 (10)	−0.0042 (10)	0.0010 (9)	0.0028 (9)
C13	0.0543 (11)	0.0490 (13)	0.0494 (11)	−0.0102 (10)	−0.0005 (9)	0.0040 (10)
C14	0.0739 (15)	0.086 (2)	0.0545 (13)	−0.0051 (14)	−0.0078 (11)	−0.0076 (13)
C15	0.0697 (14)	0.0583 (16)	0.0756 (15)	0.0019 (13)	−0.0109 (12)	0.0043 (13)
C16	0.0658 (13)	0.0453 (13)	0.0556 (12)	−0.0005 (11)	−0.0019 (10)	0.0025 (10)
C17	0.0874 (18)	0.0623 (18)	0.0851 (18)	−0.0195 (14)	−0.0028 (14)	−0.0071 (15)
C17'	0.0874 (18)	0.0623 (18)	0.0851 (18)	−0.0195 (14)	−0.0028 (14)	−0.0071 (15)

Geometric parameters (Å, º)

O1—C1	1.217 (2)	C11—C12	1.500 (3)
C1—C9	1.476 (3)	C11—H11A	0.9700
C1—C2	1.482 (3)	C11—H11B	0.9700
O2—C16	1.371 (3)	C12—C13	1.324 (3)
O2—C2	1.391 (2)	C12—H12	0.9300
C2—C3	1.337 (3)	C13—C15	1.499 (3)
O3—C16	1.189 (3)	C13—C14	1.504 (3)
C3—C4	1.489 (3)	C14—H14A	0.9600
C3—C11	1.505 (3)	C14—H14B	0.9600
O4—C4	1.218 (2)	C14—H14C	0.9600
C4—C10	1.487 (3)	C15—H15A	0.9600
C5—C6	1.384 (3)	C15—H15B	0.9600
C5—C10	1.384 (3)	C15—H15C	0.9600
C5—H5	0.9300	C16—C17'	1.488 (3)
C6—C7	1.382 (3)	C16—C17	1.488 (3)
C6—H6	0.9300	C17—H17A	0.9600
C7—C8	1.377 (3)	C17—H17B	0.9600
C7—H7	0.9300	C17—H17C	0.9600
C8—C9	1.394 (3)	C17'—H17D	0.9600
C8—H8	0.9300	C17'—H17E	0.9600
C9—C10	1.396 (3)	C17'—H17F	0.9600
O1—C1—C9	123.21 (19)	H11A—C11—H11B	107.9
O1—C1—C2	120.2 (2)	C13—C12—C11	127.8 (2)
C9—C1—C2	116.57 (16)	C13—C12—H12	116.1
C16—O2—C2	115.91 (16)	C11—C12—H12	116.1
C3—C2—O2	120.42 (18)	C12—C13—C15	121.0 (2)
C3—C2—C1	124.68 (19)	C12—C13—C14	123.5 (2)
O2—C2—C1	114.76 (16)	C15—C13—C14	115.45 (19)
C2—C3—C4	118.84 (18)	C13—C14—H14A	109.5
C2—C3—C11	122.93 (19)	C13—C14—H14B	109.5
C4—C3—C11	118.16 (17)	H14A—C14—H14B	109.5
O4—C4—C10	121.63 (19)	C13—C14—H14C	109.5
O4—C4—C3	119.97 (19)	H14A—C14—H14C	109.5
C10—C4—C3	118.40 (16)	H14B—C14—H14C	109.5
C6—C5—C10	120.2 (2)	C13—C15—H15A	109.5
C6—C5—H5	119.9	C13—C15—H15B	109.5
C10—C5—H5	119.9	H15A—C15—H15B	109.5
C7—C6—C5	120.4 (2)	C13—C15—H15C	109.5
C7—C6—H6	119.8	H15A—C15—H15C	109.5
C5—C6—H6	119.8	H15B—C15—H15C	109.5
C8—C7—C6	120.0 (2)	O3—C16—O2	121.9 (2)
C8—C7—H7	120.0	O3—C16—C17'	127.4 (2)
C6—C7—H7	120.0	O2—C16—C17'	110.7 (2)
C7—C8—C9	120.2 (2)	O3—C16—C17	127.4 (2)
C7—C8—H8	119.9	O2—C16—C17	110.7 (2)
C9—C8—H8	119.9	C16—C17—H17A	109.5
C8—C9—C10	119.8 (2)	C16—C17—H17B	109.5
C8—C9—C1	119.93 (18)	H17A—C17—H17B	109.5
C10—C9—C1	120.30 (18)	C16—C17—H17C	109.5
C5—C10—C9	119.48 (19)	H17A—C17—H17C	109.5
C5—C10—C4	119.83 (18)	H17B—C17—H17C	109.5
C9—C10—C4	120.69 (19)	C16—C17'—H17D	109.5
C12—C11—C3	112.29 (17)	C16—C17'—H17E	109.5
C12—C11—H11A	109.1	H17D—C17'—H17E	109.5
C3—C11—H11A	109.1	C16—C17'—H17F	109.5
C12—C11—H11B	109.1	H17D—C17'—H17F	109.5
C3—C11—H11B	109.1	H17E—C17'—H17F	109.5
C16—O2—C2—C3	−112.3 (2)	O1—C1—C9—C10	−175.23 (19)
C16—O2—C2—C1	71.8 (2)	C2—C1—C9—C10	6.1 (3)
O1—C1—C2—C3	178.0 (2)	C6—C5—C10—C9	1.0 (3)
C9—C1—C2—C3	−3.2 (3)	C6—C5—C10—C4	−178.70 (18)
O1—C1—C2—O2	−6.2 (3)	C8—C9—C10—C5	−1.5 (3)
C9—C1—C2—O2	172.54 (16)	C1—C9—C10—C5	177.96 (17)
O2—C2—C3—C4	−178.93 (16)	C8—C9—C10—C4	178.22 (17)
C1—C2—C3—C4	−3.4 (3)	C1—C9—C10—C4	−2.3 (3)
O2—C2—C3—C11	4.0 (3)	O4—C4—C10—C5	−4.1 (3)
C1—C2—C3—C11	179.59 (18)	C3—C4—C10—C5	175.37 (17)
C2—C3—C4—O4	−173.37 (18)	O4—C4—C10—C9	176.20 (18)
C11—C3—C4—O4	3.8 (3)	C3—C4—C10—C9	−4.4 (3)
C2—C3—C4—C10	7.2 (3)	C2—C3—C11—C12	88.5 (2)
C11—C3—C4—C10	−175.65 (17)	C4—C3—C11—C12	−88.5 (2)
C10—C5—C6—C7	0.3 (3)	C3—C11—C12—C13	118.3 (2)
C5—C6—C7—C8	−1.1 (3)	C11—C12—C13—C15	178.2 (2)
C6—C7—C8—C9	0.6 (3)	C11—C12—C13—C14	−1.0 (4)
C7—C8—C9—C10	0.7 (3)	C2—O2—C16—O3	9.9 (3)
C7—C8—C9—C1	−178.78 (19)	C2—O2—C16—C17'	−170.81 (18)
O1—C1—C9—C8	4.2 (3)	C2—O2—C16—C17	−170.81 (18)
C2—C1—C9—C8	−174.46 (17)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C11—H11B···O4^i	0.97	2.55	3.274 (3)	131
C15—H15A···O1^ii	0.96	2.59	3.485 (3)	156

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