7,7′-(3,3′-Dibenzyl-3H,3′H-4,4′-bi-1,2,3-triazole-5,5′-di­yl)bis­(4-methyl-2H-chromen-2-one)

Jessie A Key; Christopher W Cairo; Michael J Ferguson

doi:10.1107/S1600536808028250

. 2008 Sep 13;64(Pt 10):o1910. doi: 10.1107/S1600536808028250

7,7′-(3,3′-Dibenzyl-3H,3′H-4,4′-bi-1,2,3-triazole-5,5′-diyl)bis(4-methyl-2H-chromen-2-one)

Jessie A Key ^a, Christopher W Cairo ^a, Michael J Ferguson ^b,^*

PMCID: PMC2959342 PMID: 21201119

Abstract

The title compound, a bis-5,5′-triazole, C₃₈H₂₈N₆O₄, was observed as a side-product from the Sharpless–Meldal click reaction of the corresponding coumarin alkyne and benzylazide. Although the compound was present as a minor component, it crystallized in preference to the major product. The two triazole rings are almost orthogonal to each other [dihedral angle = 83.8 (1)°]. However the 4 and 4′ coumarin systems are close to coplanar with their respective triazole rings [23.6 (1) and 15.1 (1)°]. Each of the benzene rings packs approximately face-to-face with the opposing coumarin ring systems, with interplanar angles of 7.7 (1) and 25.3 (1)° and distances of 3.567 (2) and 3.929 (2) Å between the respective centroids of the opposing rings.

Related literature

Similar 5,5′-bistriazole structures have been described previously by Angell & Burgess (2007 ▶). For the synthesis of related alkyne-modified coumarins, see: Sivakumar et al. (2004 ▶); Zhou & Fahrni (2004 ▶).

Experimental

Crystal data

C₃₈H₂₈N₆O₄
M _r = 632.66
Monoclinic,
a = 12.4328 (17) Å
b = 17.565 (2) Å
c = 14.456 (2) Å
β = 94.573 (3)°
V = 3147.0 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 193 (2) K
0.36 × 0.19 × 0.06 mm

Data collection

Bruker SMART 1000 CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2003 ▶) T _min = 0.969, T _max = 0.995
21410 measured reflections
5703 independent reflections
3222 reflections with I > 2σ(I)
R _int = 0.074

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.114
S = 1.00
5703 reflections
435 parameters
H-atom parameters constrained
Δρ_max = 0.15 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: SMART (Bruker, 1997 ▶); cell refinement: SAINT (Bruker, 1997 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808028250/fb2110sup1.cif

e-64-o1910-sup1.cif^{(28.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808028250/fb2110Isup2.hkl

e-64-o1910-Isup2.hkl^{(279.2KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C5—H5⋯O2ⁱ	0.95	2.45	3.292 (3)	148
C33—H33B⋯O2ⁱⁱ	0.99	2.33	3.307 (3)	168
C10—H10C⋯O4ⁱⁱⁱ	0.98	2.52	3.337 (4)	141

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

Acknowledgments

This work was supported by the Natural Science and Engineering Research Council of Canada, the Alberta Ingenuity Centre for Carbohydrate Science and the University of Alberta.

supplementary crystallographic information

Comment

In our studies of new synthetic fluorophores through modification of a common fluorophore structure 4-methyl-unbelliferone (II), we generated new alkyne containing profluorophores. We subjected alkyne-modified coumarin structure (III) to conditions typical in a Sharpless–Meldal click reaction with the intention of forming the corresponding 1,2,3-triazole (IV). We explored several conditions for the synthesis of (IV), and obtained reasonable yields with (III) and benzyl azide when reacted with CuI and TEA in a methanol:water mixture. In some of these reactions we observed a minor side-product (23%) evidenced by the appearance of two doublet peaks between 4–5 ppm in the ¹H NMR spectrum. These resonances were attributed to the benzylic hydrogen atoms of a bis-5,5'-triazole structure (I), and the presence of this side product was confirmed by the accompanying crystal structure data. This type of side product was first reported by Angell & Burgess (2007). Those authors reported similar observations by ¹H NMR and crystallography of the bis-triazole adduct. We have identified improved conditions that avoid formation of the bis-triazole, however it is notable that commonly used conditions for click reactions may produce this type of side product.

Experimental

Synthesis of triazole (IV): The alkyne, (III) (1 equiv), and benzyl azide (4–5 equiv) were dissolved in a 1:1 solution of methanol:water (0.03 M alkyne). CuI (0.2 equiv) was then added, followed by triethylamine (TEA) (2 equiv). The reaction proceeded at room temperature and was monitored by thin layer chromatography. The reaction was complete within 2–3 h. The crude product was concentrated in vacuo, extracted with chloroform and purified by flash column chromatography (CH₂Cl₂/MeOH), a small amount of the bis-5,5'-triazole (I) was present (23%). The mixture of I and IV was dissolved in 200 µl chloroform, followed by 800 µl of hexanes. Suitable crystals were obtained after two weeks. The crystals were used for determination of the X-ray structure. The original product mixture, 77:23 of IV and I, was used for NMR and MS analysis. ¹H NMR (400 MHz, CDCl₃):** δ 7.85 (dd, 1H, ³J = 10.8 Hz, ⁴J = 2.1 Hz), 7.76 (s, 1H), 7.67 (d, 1H, ⁴J = 2.1 Hz), 7.64 (d, 1H, ³J = 10.8 Hz), 7.43- 7.32 (m, 7H), 7.22 (d, 1H, ⁴J = 1.6 Hz), 7.05 (m, 2H)^I, 6.68 (m, 1H)^I, 6.29 (d, 1H, ⁴J = 1 Hz), 6.26 (d, 0.5H, ⁴J = 1.6 Hz), 5.61 (s, 2H), 4.88 (d, 0.7H, ³J = 15.2 Hz)^I, 4.63 (d, 0.7H, ³J = 15.2 Hz)^I, 2.45 (s, 3H), 2.37 (s, 1.5H)^I. APT ¹³C NMR (100 MHz, CDCl₃): δ 160.7, 160.3, 153.9, 153.5, 152.0, 151.6, 134.3, 132.6, 132.3, 129.3, 129.0, 128.8, 128.6, 128.2, 128.0, 125.2, 121.5, 121.3, 120.1, 119.6, 115.5, 115.0, 113.8, 113.6, 54.5, 53.0, 18.6, 18.5. HRMS calculated for C₃₈H₂₈N₆O₄: 632.22; observed: 632.21768 ([2M-2H]⁺). HRMS calculated for C₁₉H₁₅N₃O₂: 317.12; observed: 340.11635 ([M+Na]⁺). Rf = 0.68 (10:1 CH₂Cl₂/MeOH). **NMR peaks attributed to compound I are denoted by a superscript, and were not observed in purified samples of IV.