Startseite Crystal structure of (3-(dimethoxymethyl)-5-methoxy-1H-indol-1-yl) (2-iodo-5-methoxyphenyl)methanone, C20H20INO5
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Crystal structure of (3-(dimethoxymethyl)-5-methoxy-1H-indol-1-yl) (2-iodo-5-methoxyphenyl)methanone, C20H20INO5

  • Jia-Cheng Yuan , Yue Zhang , Yang Yu , Fei-Er Hai und Wei Cong ORCID logo EMAIL logo
Veröffentlicht/Copyright: 16. September 2025

Abstract

C20H20INO5, monoclinic, P21/c (no. 14), a = 14.49960(10) Å, b = 18.5114(2) Å, c = 7.09190(10) Å, β = 95.2400(10)°, V = 1895.57(4) Å3, Z = 4, Rgt(F) = 0.0348, wRref(F2) = 0.0913, T = 293(2) K.

CCDC no.: 2484942

The crystal structure is shown in figure. Displacement ellipsoids are drawn at the 30 % probability level. Table 1 contains the crystallographic data and the list of the atoms including atomic coordinates and displacement parameters can be found in the cif-file attached to this article.

Table 1:

Data collection and handling.

Crystal: Clear light colourless block
Size: 0.14 × 0.13 × 0.10 mm
Wavelength: CuKα radiation (1.54178 Å)
μ: 13.5 mm−1
Diffractometer, scan mode: Rigaku synergy R, ω scan
θmax, completeness: 73.4°, 100 %
N(hkl)measured, N(hkl)unique, Rint: 13531, 3677, 0.064
Criterion for Iobs, N(hkl)gt: Iobs > 2σ(Iobs), 3,546
N(param)refined: 248
Programs: Rigaku, 1 Shelx 2 , 3

1 Source of material

The target compound (3-(dimethoxymethyl)-5-methoxy-1H-indol-1-yl)(2-iodo-5-methoxyphenyl)methanone was synthesized via acylation of 3-(dimethoxymethyl)-5-methoxy1H-indole with the corresponding acyl chloride. A 50 mL round-bottomed flask was charged with sodium hydride (684 mg, 17.1 mmol) and anhydrous N,N-dimethylformamide (DMF, 7 mL). The mixture was stirred in an ice-water bath for 5 min. Subsequently, a solution of 3-(dimethoxymethyl)-5-methoxy-1H-indole (840 mg, 3.8 mmol) in anhydrous DMF (5 mL) was added dropwise to the reaction system. Upon completion of the addition, stirring was continued for an additional 5 min. Thereafter, a pre-prepared solution of 2-iodo-5-methoxybenzoyl chloride (2,475 mg, 8.36 mmol) in anhydrous DMF (5 mL) was added dropwise. Following the complete addition, the reaction mixture was gradually warmed to room temperature and stirred for 5 h. The progress of the reaction was monitored by thin-layer chromatography (TLC) using UV detection at 254 nm. Upon completion of the reaction, the mixture was carefully quenched with a saturated ammonium chloride solution, resulting in the precipitation of the crude product. The crude product was triturated with petroleum ether/ethyl acetate (1:1, v/v), followed by filtration and washing to afford the pure product (1,426 mg, yield 78 %). Crystals were obtained by recrystallization from a n-hexane/ethyl acetate (1:1, v/v) solution.

2 Experimental details

The H atoms were placed in idealized positions and treated as riding on their parent atoms, with d (C–H) = 0.96 Å (methyl), Uiso(H) = 1.5Ueq(C), and d(C–H) = 0.98 Å (methyne), Uiso(H) = 1.2Ueq(C), and d(C–H) = 0.93 Å (aromatic), Uiso(H) = 1.2Ueq(C).

3 Comment

Nitrogen-containing heterocycles are ubiquitous in bioactive molecules and pharmaceutical compounds. 4 In structural optimization of drug molecules, replacing the original benzene ring with aromatic nitrogen-containing heterocycles like pyridine, pyrimidine, pyrrole, pyrazole, 5 as well as substituting the naphthalene ring with quinoline or indole, 6 have become one of the most common modification strategies. The above modification methods could achieve multiple objectives including enhanced biological activity, improved pharmacokinetic stability, increased water solubility, and circumvention of patent restrictions. 7 , 8 , 9 On the other hand, consistent with principles of organic chemistry, the methoxy group acted as both a strong electron-donating group and a steric hindrance factor in electrophilic aromatic substitution reactions. 10 It activated the aromatic ring through its electron-donating capability while simultaneously exerting steric control to direct the regiochemistry of electrophilic attack. 11 As one of the most prevalent substituents in bioactive molecular structures, methoxy groups were present in over 230 marketed small-molecule drugs. 12 Methoxy groups could form hydrogen bonds and hydrophobic interactions with target proteins, 13 while exerting significant conformational regulation and restriction effects on molecules. 14 Based on the above background, in our preliminary research, 15 we designed and synthesized a series of N-acylindole compounds featuring dual methoxy substitutions. In this work, the crystals of (3-(dimethoxymethyl)-5-methoxy-1H-indol-1-yl)(2-iodo-5-methoxyphenyl)methanone were obtained and its structure is reported here.

Single-crystal X-ray diffraction analysis reveals that there is one molecule in the asymmetric unit (cf. the figure). All bond lengths and bond angles are within the typical range. 16 , 17 , 18 In the target molecule, the iodine-substituted benzene ring and the indole ring are linked via a carbonyl group. Due to the conjugation between the N(1) atom of the indole moiety and the carbonyl group, the C(9)–N(1) bond length (1.385(3) Å) is significantly shorter than that of a normal C–N single bond, which is comparable to the C(1)–N(1) (1.405(3) Å) and C(7)–N(1) (1.411(3) Å) bonds within the indole ring. The torsion angles of O(1)–C(9)–N(1)–C(1) and O(1)–C(9)–N(1)–C(7) are 178.3(2)° and −5.0(4)°, respectively, indicating that the amide segment and the indole ring are nearly coplanar. This structural feature is presumably attributed to the conjugation effect and minimal steric hindrance. In contrast, the torsion angles of O(1)–C(9)–C(10)–C(11) and O(1)–C(9)–C(10)–C(15) are 88.6(3)° and −91.0(3)°, respectively, suggesting that the carbonyl group and the benzene ring adopt an almost perpendicular conformation. This conformation is likely caused by steric repulsion between the carbonyl oxygen atom and the iodine atom. Overall, as a result of the aforementioned effects, the indole ring and the methoxy-substituted benzene ring are nearly perpendicular to each other, with a dihedral angle of 87.99(3)°.


Corresponding author: Wei Cong, School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, P.R. China, E-mail:

Acknowledgments

This work was supported by National Science Foundation of China (No. 21702018), a Key Research and Development Program of Shandong Province (No. 2019GSF108031).

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Received: 2025-07-23
Accepted: 2025-09-04
Published Online: 2025-09-16
Published in Print: 2025-12-17

© 2025 the author(s), published by De Gruyter, Berlin/Boston

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

Artikel in diesem Heft

  1. Frontmatter
  2. New Crystal Structures
  3. The crystal structure of (1Z, 2Z)-3-phenyl-2-propenal 2-(4-bromo-2-fluorophenyl)hydrazone, C15H12BrFN2
  4. Refinement of crystal structure of 2-(2,3-dihydro-3-oxo-1 H -inden-1-ylidene)-1 H -indene-1,3(2 H )-dione C18H10O3
  5. The crystal structure of 3-(1-fluoro-2-(naphthalen-2-yl)-2-oxoethyl)-2-methoxy-3,4-dihydroisoquinolin-1(2H)-one, C22H18FNO3
  6. Crystal structure of the dinuclear copper(II) complex bis(μ2-2,2′ -{[1,3-phenylenebis-(methylene)]bis(oxy)}dibenzoaot-κ4O,O′:O′′,O′′′)-bis(dimethylformamide-κ1O)dicopper(II), C50H44Cu2N2O14
  7. Crystal structure of poly[triaqua-(μ9-biphenyl-3,3′,5,5′-tetracarboxylic-κ8 O,O:O,O′: O,O″:O,O‴)samarium(III)sodium(I)], C16H12NaSmO11
  8. The crystal structure of 5-benzyl-1-(4-fluorobenzyl)-4-((4-fluorobenzyl)oxy)-1,5-dihydro-2H-pyrrol-2-one, C25H21F2NO2
  9. The crystal structure of diammonium 2,5-dihydroxyterephthalate, C8H12N2O6
  10. Crystal structure of (E)-4-(4-(1H-1,2,4-triazol-1-yl)benzylidene)-6,8-dimethoxy-3,4-dihydrobenzo[b]oxepin-5(2H)-one, C21H19N3O4
  11. Crystal structure of poly[oktakis(μ2-oxido-κ2O:O)-tetrakis(oxido-κ1O)-bis(μ2-1,1′-[1,4-phenylenebis(methylene)]di(1H-imidazole-κ2N:N′))-tetravanadium(V)-dizinc(II)] monohydrate, C28H30Zn2N8O13V4
  12. Crystal structure of acotiamide hydrochloride dimethylacetamide solvate (1/1), C25H40ClN5O6S
  13. Crystal structure of catena-poly[monoaqua (u2-(3-(3,5-dicarboxyphenyl)pyridine-2,6-dicarboxylic-k4O:O′:O″:N)zinc(II))] monohydrate, C15H11NO10Zn
  14. Crystal structure of dichlorido{2,6-bis(3,5-diisopropyl-N-pyrazolyl)pyridine}zinc(II), C23H33Cl2N5Zn
  15. Crystal structure of nitrato-κ2O,O′-[hydridotris(3,5-diethylpyrazol-1-yl)borato-κ3N,N′,N″]copper(II), C21H34BCuN7O3
  16. Crystal structure of 2,7-bis(3,5-diethyl-1H-pyrazol-4-yl)-benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetrone, C28H26N6O4
  17. Crystal structure of 2-(4-chlorophenyl)benzothiazole, C13H8ClNS
  18. Synthesis and crystal structure (3R,4′S)-4′-(3,5-dibromophenyl)-1′-methyl-2H-dispiro [benzofuran-3,3′-pyrrolidine-2′,2″-indene]-1″,2,3″-trione, C26H17Br2NO4
  19. Crystal structure of bis(((3a,7a-dihydro-1H-benzo[d][1,2,3]triazol-1-yl)methyl) triphenylphosphonium) tetrachloridomanganate(II), C50H42Cl4MnN6P2
  20. The crystal structure of 4,9-bis(4-chlorophenyl)-1,6-bis(2-cyanobenzyl)-2,4a,5,6,7,7a-hexahydro-1H-2,7,5-(epiprop[2]ene[1,1,3]triyl)pyrrolo[3,4-b]pyridine-3,10-dicarbonitrile, C40H26Cl2N6
  21. The crystal structure of poly((μ2-3-(3-nitro-4-carboxylphenyl)benzoate-κ3O, O′:O″)-μ2-1,4-bis(1-imidazolyl)benzene-κ2N:N′-cadmium(II)), C26H17N5O6Cd
  22. The crystal structure of 6-hydroxy-5H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione monohydrate, C7H6N2O4
  23. Crystal structure of 4-((cyclohexylsulfonyl)methyl)-1,2,3,4-tetrahydrobenzo [4,5]imidazo[1,2-a]pyridine, C18H24N2O2S
  24. Crystal structure of 4,7-diphenyl-1,10-phenanthroline-κ2N,N′)-bis(2,4-di(fluorine)-1-phenylpyridine-κ2C,N)-iridium(III) hexafluorophosphate–dichloromethane (1/1), C47H30Cl2F10IrN4P
  25. Crystal structure of (4-(1-phenyl-1H-benzo[d]imidazol-2-yl)phenyl)boronic acid, C19H15BN2O2
  26. The crystal structure of (E)-(2-((pyridin-2-ylmethylene)amino)phenyl)arsonic acid, C12H11AsN2O3
  27. The crystal structure of N(benzyl(phenyl)carbomothioyl)benzamide, C21H18N2OS
  28. The crystal structure of bis(2-picolinium) hexachlorostannate dichloromethane monosolvate, C13H18Cl8N2Sn
  29. Crystal structure of poly[tetraaqua-bis(μ4-3–1-(carboxylatomethyl)-1H-1,2,4-triazole-3-carboxylato)-κ4O:O′,O″,N)zinc(II)], C5H7N3O6Zn
  30. The crystal structure of the co-crystal isonicotinamide – 2-(nitrophenyl)methanol (1/1), C6H6N2O·C7H7NO3
  31. The crystal structure of 4-(3-carboxy-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl)piperazin-1-ium 2-fluorobenzoate hydrate, C23H25F2N3O6
  32. Crystal structure of [diaqua-{1H-benzo[d]imidazol-3-ium-5,6-dicarboxylato-κ2O,O′}magnesium(II)] C18H14MgN4O10
  33. Crystal structure of (3-(dimethoxymethyl)-5-methoxy-1H-indol-1-yl) (2-iodo-5-methoxyphenyl)methanone, C20H20INO5
  34. The crystal structure of 3,7,11-trimethylbenzo[5,6][1,4]thiazino[2,3,4-kl]phenothiazine 5,5,9,9-tetraoxide, C21H17NO4S2
  35. Crystal structure of tris(piperazine-1,4-diium)bis(2-hydroxy-1,2,3-propane-tricarboxylate) pentahydrate, C24H56N6O19
  36. Crystal structure of 2-chloro-5-((5-isopropyl-2-methylphenoxy)methyl)pyridine, C16H18ClNO
  37. Crystal structure of (E)-4-(4-(1H-pyrrol-1-yl)benzylidene)-6,8-dimethoxy-3,4-dihydrobenzo[(b)]oxepin-5(2H)-one, C23H21NO4
  38. Crystal structure of (E)-N′-(3,4-dichlorobenzylidene)-3,4,5-trimethoxybenzohydrazide, C17H16Cl2N2O4
  39. The crystal structure of 2-(2-hydroxyphenyl)-3-(pyridin-2-yl)-2,3- dihydroquinazolin-4(1H)-one, C19H15N3O2
  40. Crystal structure of 5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-8-methylchroman-4-one, C17H16O5
  41. Crystal structure of bis[(3,4-dimethoxybenzyl)triphenylphosphonium]di-μ2-bromido-dibromidodicopper(I)
  42. Crystal structure of bis [(1,3-dioxolan-2-ylmethyl)triphenylphosphonium] tetrabromidodicopper(I), C22H22Br2CuO2P
  43. Crystal structure of [1-(4-carboxyphenyl)-4-oxo-1,4-dihydropyridazine-3-carboxylic acid], C12H8N2O5
  44. The crystal structure of one-dimensional cooridnation polymer bis(thiocyanato)-bis((1E,2E)-1,2-bis(1-(pyridin-3-yl)ethylidene)-hydrazine κ2N:N)iron(II), (C30H28N10S2Fe)n
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  46. Crystal structure of [(1-naphthalen-1-yl-methyl)triphenylphosphonium] dichloridocopper(I), [C29H24P]+[CuCl2]
  47. RbTm3S5: the first rubidium lanthanoid(III) sulfide with CsEr3Se5-type crystal structure
  48. Crystal structure of 2,2′-((ethane-1,2-diylbis(methylammoniumdiyl))bis(methylene))bis(pyridin-1-ium) diiodido-tris(μ2-iodido-κ2I:I)dicopper(II) chloride dihydrate, C16H30Cu2I6N4O2
  49. The crystal structure of 4-(trifluoromethyl)pyridine-2-carboxylic acid, C7H4F3NO2
  50. The crystal structure of (E)-2-ethoxy-1-methoxy-4-(2-(methylsulfonyl)vinyl)benzene, C12H16O4S
  51. Crystal structure of potassium 1H,1H,2H,2H-perfluorooctanesulfonate, C8H4O3F13SK
  52. Crystal structure of 4-(4-(quinolin-8-yloxy)-1,2,5-thiadiazol-3-yl)morpholine, C15H14O2N4S
  53. The crystal structure of 1,4-bis(bromomethyl)-2,5-dimethylbenzene, C10H12Br2
  54. The crystal structure of imidazo[4,5-e][1,3]diazepine-4,6,8-triamine methanol solvate, C7H11N7O
  55. The crystal structure of chlorido-bis(1,10-phenantroline-κ2N,N′)-(2-formylphenoxyacetato-κ2O,O) lead(II), C33H23N4O4ClPb
  56. Crystal structure of pyridinium tetrakis(1,1,1-trifluoro-2,4-pentadionato-κ2O,O′)yttrium(III) C20F12H16YO8C5H6N
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