Crystal structure of 4-(2,2-difluoroethyl)-2,4-dimethyl-6-(trifluoromethyl)isoquinoline-1,3(2H,4H)-dione, C14H12F5NO2

Jianlian Liu; Chaojun Du; Hong Hao

doi:10.1515/ncrs-2021-0179

Open Access Published by De Gruyter (O) June 21, 2021

Crystal structure of 4-(2,2-difluoroethyl)-2,4-dimethyl-6-(trifluoromethyl)isoquinoline-1,3(2H,4H)-dione, C₁₄H₁₂F₅NO₂

Jianlian Liu , Chaojun Du and Hong Hao

From the journal Zeitschrift für Kristallographie - New Crystal Structures

https://doi.org/10.1515/ncrs-2021-0179

Abstract

C₁₄H₁₂F₅NO₂, monoclinic, P2₁/c (no. 14), a = 11.8292(10) Å, b = 11.0987(8) Å, c = 11.6480(10) Å, β = 115.282(11)°, V = 1382.8(2) Å³, Z = 4, R_gt(F) = 0.0913, wR_ref(F²) = 0.1609, T = 293(2) K.

CCDC no.: 2086867

The molecular structure is shown in the figure. Table 1 contains crystallographic data and Table 2 contains the list of the atoms including atomic coordinates and displacement parameters.

Table 1:

Data collection and handling.

Crystal:	Colourless block
Size:	0.25 × 0.22 × 0.20 mm
Wavelength:	Mo Kα radiation (0.71073 Å)
μ:	0.15 mm⁻¹
Diffractometer, scan mode:	φ and ω
θ_max, completeness:	25.0°, >99%
N(hkl)_measured, N(hkl)_unique, R_int:	7263, 2410, 0.024
Criterion for I_obs, N(hkl)_gt:	I_obs > 2 σ(I_obs), 1846
N(param)_refined:	201
Programs:	Bruker [1], SHELX [2]

Table 2:

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

Atom	x	y	z	U_iso*/U_eq
C1	0.7199 (4)	−0.0363 (4)	0.9590 (4)	0.0473 (11)
H1	0.645125	−0.075047	0.909284	0.057*
C2	0.8152 (4)	−0.0997 (4)	1.0529 (4)	0.0468 (11)
C3	0.9265 (4)	−0.0426 (5)	1.1295 (4)	0.0522 (12)
H3	0.989931	−0.084825	1.193888	0.063*
C4	0.9419 (4)	0.0762 (5)	1.1093 (4)	0.0507 (12)
H4	1.016480	0.114813	1.159842	0.061*
C5	0.8470 (4)	0.1399 (4)	1.0138 (4)	0.0388 (10)
C6	0.7348 (4)	0.0849 (4)	0.9382 (4)	0.0394 (10)
C7	0.6287 (4)	0.1541 (4)	0.8369 (4)	0.0422 (10)
C8	0.6618 (4)	0.2836 (4)	0.8179 (4)	0.0496 (11)
C9	0.8703 (4)	0.2688 (4)	0.9972 (4)	0.0463 (11)
C10	0.8046 (5)	0.4551 (4)	0.8751 (6)	0.0720 (16)
H10A	0.763655	0.473390	0.786061	0.108*
H10B	0.893186	0.465536	0.904768	0.108*
H10C	0.774410	0.508287	0.920767	0.108*
C11	0.5162 (4)	0.1616 (5)	0.8723 (5)	0.0598 (13)
H11A	0.489418	0.081730	0.880624	0.090*
H11B	0.448499	0.203982	0.806907	0.090*
H11C	0.541109	0.203776	0.951388	0.090*
C12	0.7967 (5)	−0.2293 (5)	1.0733 (6)	0.0664 (15)
C13	0.5837 (4)	0.0916 (4)	0.7068 (4)	0.0482 (11)
H13A	0.540940	0.017679	0.708874	0.058*
H13B	0.523669	0.143533	0.642740	0.058*
C14	0.6861 (5)	0.0622 (5)	0.6685 (4)	0.0614 (14)
H14	0.740467	−0.000405	0.724089	0.074*
F1	0.8981 (3)	−0.2943 (3)	1.1072 (4)	0.0901 (11)
F2	0.7691 (4)	−0.2434 (3)	1.1743 (5)	0.1122 (14)
F3	0.7088 (4)	−0.2797 (3)	0.9782 (4)	0.163 (3)
F4	0.6379 (4)	0.0256 (4)	0.5459 (3)	0.1155 (14)
F5	0.7533 (4)	0.1608 (4)	0.6720 (4)	0.1011 (13)
N1	0.7778 (3)	0.3295 (3)	0.8959 (4)	0.0470 (9)
O1	0.5855 (3)	0.3455 (3)	0.7366 (4)	0.0756 (12)
O2	0.9643 (3)	0.3203 (3)	1.0675 (3)	0.0713 (11)

Source of material

The title compound was synthesized according to the literature method [3]. Colorless single crystals suitable for X-ray diffraction analysis were obtained by slow evaporation of its anhydrous tetrahydrofuran solution at room temperature.

Experimental details

All H atoms were placed in calculated positions (C–H = 0.93 Å for aryl, 0.96 Å for methyl, 0.97 Å for methylene and 0.98 Å for methine). The U_iso values were constrained to be 1.5U_eq of the carrier atom for methyl groups and 1.2U_eq for the remaining H atoms.

Comment

As a class of important nitrogen containing heterocycles, isoquinoline-1,3-diones are widely found in biologically active natural products, pharmaceuticals and plant alkaloids due to their high pharmaceutical and biological activities [3], [4], [5], [6]. In recent years, much efforts has been made to explore the incorporation of difluoromethyl group into the skeleton of isoquinoline-1,3-dione to construct CF₂H-containing isoquinoline-1,3-diones [3, 7–11]. In order to study the relationship between the structural and biological properties of CF₂H-containing isoquinoline-1,3-diones, we report the molecular and crystal structures of the title compound.

The asymmetric unit of the title compound contains one molecule (see the Figure). The bond lengths and angles are in the normal ranges [12]. The C=O bond lengths of 1.205(5) Å (C8=O1) and 1.206(5) Å (C9=O2) illustrate typical double-bond character. The six-membered ring (C5–C6–C7–C8–N1–C9) is slightly deviated from planarity, the mean deviation from the plane of 0.0301 Å C9 has the largest deviation of 0.0424 Å. The two rings are almost coplanar. Shortest distance (2.6 A) is larger than sum of vdW radii.

Corresponding author: Jianlian Liu, School of Chemical Engineering, Northwest University, 710069, Xi’an, Shaanxi, People’s Republic of China; and School of Biological and Chemical Engineering, Nanyang Institute of Technology, 473004, Nanyang, Henan, People’s Republic of China, E-mail: zgqjd2005@sohu.com

Funding source: Education Department of Henan Province

Award Identifier / Grant number: 20B530004

Funding source: Nanyang Science and Technology Bureau

Award Identifier / Grant number: JCQY004

Funding source: Nanyang Key Laboratory of Catalytic Functional Materials

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was financial supported by the Education Department of Henan Province (20B530004), Nanyang Science and Technology Bureau (JCQY004), and Nanyang Key Laboratory of Catalytic Functional Materials.
Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

1. Bruker. APEX2, SAINT and SADABS; Bruker AXS Inc.: Madison, Wisconsin, USA, 2008.Search in Google Scholar

2. Sheldrick, G. M. A short history of SHELX. Acta Crystallogr. 2008, A64, 112–122; https://doi.org/10.1107/s0108767307043930.Search in Google Scholar

3. Zou, G., Wang, X. Visible-light induced di- and trifluoromethylation of N-benzamides with fluorinated sulfones for the synthesis of CF2H/CF3-containing isoquinolinediones. Org. Biomol. Chem. 2017, 15, 8748–8754; https://doi.org/10.1039/c7ob02226c.Search in Google Scholar

4. Hua, M.-Q., Mou, F.-Y., Wang, N.-H., Chen, Y., Xiong, H.-Y., Huang, Y., Lei, C.-L., Zhang, Q. Visible-light-induced photocatalytic difluoroalkylation of 3-substituted benzo[d]isoxazoles via direct and regioselective C–H functionalization. Tetrahedron Lett. 2018, 59, 4449–4453; https://doi.org/10.1016/j.tetlet.2018.10.007.Search in Google Scholar

5. Vernekar, S. K. V., Liu, Z., Nagy, E., Miller, L., Kirby, K. A., Wilson, D. J., Kankanala, J., Sarafianos, S. G., Parniak, M. A., Wang, Z. Design, synthesis, biochemical, and antiviral evaluations of C6 benzyl and C6 biarylmethyl substituted 2-hydroxylisoquinoline-1,3-diones: dual inhibition against HIV reverse transcriptase-associated RNase H and polymerase with antiviral activities. J. Med. Chem. 2015, 58, 651–664; https://doi.org/10.1021/jm501132s.Search in Google Scholar

6. Wang, S., Dai, P., Yan, C., Wang, Y., Shao, J., Wu, Y., Deng, C., Zhang, W. Metal- free, visible-light-induced radical trifluoromethylation/cyclization of N-benzamides with CF3SO2Na to synthesize CF3-containing isoquinoline- 1,3-diones. ChemistrySelect 2019, 4, 10329–10333; https://doi.org/10.1002/slct.201902545.Search in Google Scholar

7. Zeng, W., Yan, W., Paeth, M., Zacate, S. B., Hong, P.-H., Wang, Y., Yang, D., Yang, K., Yan, T., Song, C., Cao, Z., Cheng, M.-J., Liu, W. Copper-catalyzed, chloroamide-directed benzylic C–H difluoromethylation. J. Am. Chem. Soc. 2019, 141, 11398–11403; https://doi.org/10.1021/jacs.9b05363.Search in Google Scholar

8. Zhu, M., You, Q., Li, R. Synthesis of CF2H-containing oxindoles via photoredox-catalyzed radical difluoromethylation and cyclization of N-arylacrylamides. J. Fluor. Chem. 2019, 228, 109391; https://doi.org/10.1016/j.jfluchem.2019.109391.Search in Google Scholar

9. Hu, W.-Q., Xu, X.-H., Qing, F.-L. Visible light induced hydrodifluoromethylation of alkenes derived from oxindoles with (difluoromethyl)triphenylphosphonium bromide. J. Fluor. Chem. 2018, 208, 73–79; https://doi.org/10.1016/j.jfluchem.2018.01.013.Search in Google Scholar

10. Schmitt, E., Rugeri, B., Panossian, A., Vors, J.-P., Pazenok, S., Leroux, F. R. In situ generated fluorinated iminium salts for difluoromethylation and difluoroacetylation. Org. Lett. 2015, 17, 4510–4513; https://doi.org/10.1021/acs.orglett.5b02184.Search in Google Scholar

11. Okusu, S., Tokunaga, E., Shibata, N. Difluoromethylation of terminal alkynes by fluoroform. Org. Lett. 2015, 17, 3802–3805; https://doi.org/10.1021/acs.orglett.5b01778.Search in Google Scholar

12. Li, H., Han, X., Cao, B. Crystal structure of 4-(2,2-difluoroethyl)-2,4,6- trimethylisoquinoline-1,3(2H,4H)-dione, C14H15F2NO2. Z. Kristallogr. NCS 2021, 236, 499–501; https://doi.org/10.1515/ncrs-2020-0635.Search in Google Scholar

Received: 2021-05-10

Accepted: 2021-05-31

Published Online: 2021-06-21

Published in Print: 2021-09-27

This work is licensed under the Creative Commons Attribution 4.0 International License.