Introduction

1,2,3-Triazole exists in two tautomeric forms, namely 1H-1,2,3-triazole and 2H-1,2,3-triazole, see Fig. 1. Derivatives of both forms have attracted much attention [1–3], in particular for their biological activities, which include as antiviral [4–6], antimalarial [7], antitubercular [8–10], antifungal [11, 12] anti-HIV [13], β-lactamase inhibition [14], anti-epileptic [15], anti-HSV [16], anti-inflammatory [17], antimicrobial [18, 19] and α-glycosidase inhibition agents [20–23]. Patents lodged in the period 2008–2011 for 1H-1,2,3-triazole and 2H-1,2,3-triazole derivatives have been included in a general survey for all triazolyl compounds [24].

Fig. 1
figure 1

a 1H-1,2,3-triazole, b 2H-1,2,3-triazole

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A recent α-glycosidase inhibition study [23] involved a number of different 1-phenyl-1H- and 2-phenyl-2H-1,2,3-triazol derivatives. The crystal structures of three of the compounds from that study [20] have been determined, namely, (1-phenyl-1H-1,2,3-triazol-4-yl)methyl benzoate, 1a, (2-(4-fluorophenyl)-2H-1,2,3-triazole-4-yl)methanol, 2a and 2-phenyl-2H-1,2,3-triazole-4-carbaldehyde, 2b, see Table 1. Compounds, 1a and 2a, exhibited little activity, while compound 2b, exhibited a greater inhibition, as did all the 2-aryl-2H-1,2,3-triazole-4-carbaldehyde derivatives. It was suggested that the aldehydes act upon both yeast maltase and PPA, with the aldehyde groups reacting with amine groups in the enzyme polypeptide chain to form Schiff bases.

Table 1 Compounds mentioned in this article
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We now wish to report our structural findings.

Results and Discussion

The compounds were prepared as previously reported, see Scheme 1 [20].

Scheme 1
scheme 1

Reagents; i = d-glucose; ii = aq. CuSO4; Δ, iii = NaIO4; iv = NaBH4, MeOH; v = HC≡C–CH2OH, CuI; vi = PhCOCl

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Molecular Confirmations

Compounds 2a and 2b crystallize in the monoclinic space group, P21 with Z = 2, while compound 2b crystallizes in the monoclinic space group, P21/c with Z = 4. The asymmetric unit in each case consists of a single molecule, as illustrated in Fig. 2. Selected bond lengths and angles are listed in Table 2. The bond lengths and angles associated with the 1,2,3-triazole rings are in the regions normally found for 1-aryl-1H-1,2,3,triazoles [see for example 25–28] and for 2-aryl-2H-1,2,3,triazoles [see for example Refs. 28–33].

Fig. 2
figure 2

Atom arrangements and the numbering schemes for 1a, 2a and 2b. Probability ellipsoids are drawn at the 50 % level. The intramolecular hydrogen bond in 1a is drawn as a thin dashed line

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Table 2 Selected geometric parameters, Å°
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In each of 1a, 2a and 2b, the triazolyl ring is essentially planar. The dihedral angles between the triazolyl and aryl rings are listed in Table 3.

Table 3 Interplanar angles, °
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A large range of dihedral angles have been reported for both 1-aryl-1H-1,2,3-triazole and 2-aryl-2H-1,2,3-triazole compounds, for example the angles are 0.34(17) and 87.1(2)°, respectively, in 4-difluoromethyl-1-(4-methylphenyl)-1H-1,2,3-triazole, 1b, [34] and in one independent molecule of 1-[5-methyl-1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl]ethanone, 1c [35], see Table 1. The carbon atoms of the methylene units in 2b and 1a are essentially co-planar with the attached triazolyl group. Compound 1a has a “V” shape with the angle between the near planar phenyltriazolyl-CH2 and phenyl-CO2CH2 moieties of 88.11(4)°.

Crystal Structures

Compound 1a

The intermolecular interactions in 1a are all weak, being C–H···N hydrogen bonds, C–H···π and π–π interactions. As illustrated in Fig. 3a, chains of molecules are propagated in the direction of the b axis, from combinations of C5–H5···N3, C5–H5···N2 and C8–H8···N3 hydrogen bonds, see Table 4 for the symmetry operations. Of these hydrogen bonds, the C5–H5···N3 is the most significant. With C5–H5 acting as donor to two acceptors, N2 and N3, \({\text{R}}^{1}_{2}\) (3) rings are generated. The C5–H5···N3, C5–H5···N2, and C8–H8···N3 hydrogen bonds individually generate C4, C4 and C6 chains of molecules.

Fig. 3
figure 3

Compound 1a. a A chain of molecules generated in the direction of the b axis, from combinations of C5–H5···N3, C5–H5···N2 and C8–H8···N3 hydrogen bonds, b a further chain of molecules, propagated in the direction of the a axis, formed from C6–H6A···π(triazole)and weak π(phenyl)···π(triazole) interactions. Table 4 lists the symmetry operations. Intermolecular interactions are drawn as thin dashed lines

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Table 4 Geometric parameters (Å, °) for intra- and intermolecular interactions
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Further, chain of molecules, this time propagated in the direction of the a axis, are formed from combinations of C6–H6A···π(triazolyl) and π(phenyl)···π(triazolyl) stacking interactions, see Fig. 3b; Table 4. This combination of interactions provides a chevron-type arrangement. The perpendicular distance between the best planes of combined triazolyl/ phenyl rings between layers is 3.359(3) Å, and with the Cg···Cg separations of 3.738(3) Å, these π···π interactions are important. The packing of the molecules looking down the b axis is shown in Fig. 4.

Fig. 4
figure 4

Packing of molecules of 1a, looking down the b axis

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The structure of a related compound, 1-phenyl-4-(pyridine-3-yl-CO2CH2)-1H-1,2,3-triazole) (1d) [36] has been reported. There are some structural similiarities between 1a and 1d: (i) the molecule of 1d is also “V” shaped with the angle between the planar phenyltriazolyl CH2 and phenyl-CO2CH2 moieties of 83.84°, (ii) the dihedral angle between the triazolyl and phenyl rings is 16.54 (11)°, and (iii) there are similar C–H··· π (triazole) and π(phenyl)···π(triazolyl) interactions [Cg···Cg = 3.895(1) Å]. However other intermolecular interactions are different in 1d, being C–H···N(py), C–H···O(carbonyl) and C–H···π(triazolyl) hydrogen bonds, which generate a different supramolecular array to that of 1a.

Compound 2a

The intermolecular interactions in 2a are C8–H8···O2 and C11–H11···O2 hydrogen bonds and C10–F1··· π(phenyl) interactions. Table 4 lists the symmetry operations and geometric parameters. Combinations of the C8–H8···O2 and C11–H11···O2 hydrogen bonds generate sheets of molecules, composed of \({\text{R}}^{ 4}_{ 3}\) (24) rings, see Fig. 5a. The sheet undulates in the direction of the b axis, as shown in Fig. 4b. Both the C–H···O hydrogen bonds building the sheets are on the weak side. Stacks of molecules are generated from C10–F1···π(phenyl) interactions, see Fig. 5c. The Cg(phenyl)–Cg(triazolyl) distances in adjacent layers within the stacks are 4.2623(17) Å, which suggest any π(phenyl)– π(triazolyl) must be very weak. Figure 6 illustrates the packing of molecules of 2a.

Fig. 5
figure 5

Compound 2a. a An undulating sheet of molecules of 2a, formed from weak C11–H11···O2 and C8–H8···O2 hydrogen bonds, and composed of \({\text{R}}^{ 4}_{ 3}\) (24) rings, b an alternate view of the sheet shown in a, clearly indicating its undulating nature and its alignment along the b axis, c a stack of molecules, with π(phenyl)–π(triazole) stacking interactions, augmented by C10–F1···π(phenyl) interactions. Intermolecular interactions are drawn as thin dashed lines. Table 4 lists the symmetry operations

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Fig. 6
figure 6

Packing of molecules of 2a, looking down the b axis

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Compound 2b

Present in 2b are classical O1–H1···O1 hydrogen bonds, and C6–H6B···π(triazolyl) and π(phenyl)···π(triazolyl) interactions. All three interactions together generate a chevron-type arrangement of molecules as illustrated in Fig. 7. The most significant of these interactions are O1–H1···O1 hydrogen bonds, which forms chains of molecules in the direction of the b axis. The packing of the molecules of 2b, looking down the b axis is illustrated in Fig. 8. As in compound 2a, none of the triazolyl nitrogen atoms are involved in any intermolecular interaction in 2b.

Fig. 7
figure 7

Chevron type arrangement of molecules of 2b, generated from strong classical O1–H1···O 1 intermolecular hydrogen bonds and weaker C6–H6B···π(triazole) and π(triazole)···π(phenyl) interactions. Table 4 lists the symmetry operations. Intermolecular interactions are drawn as thin dashed lines

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Fig. 8
figure 8

Packing arrangement of molecules of 2b, looking down the b axis

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Related Compounds

Comparisons of the structure of 2a can be made with those reported for 1-(4-methylphenyl)-4-OCH-1H-1,2,3-triazole, 1e, [37] and 1-(4-nitrophenyl)-4-trimethylsilyl-1H-1,2,3-triazol-5-carbaldehyde, 1f, [38].

The structure of 1e, which was only briefly discussed in the original article [37], exhibits significant differences with that of 2a. Features of the structure of 1e are (i) a near planar molecule, as shown by the dihedral angle of 7.1° between the triazolyl and the phenyl rings, (ii) C–H(phenyl)···O(=C) and C5–H5···N3 hydrogen bonds forming chains containing \({\text{R}}^{ 2}_{ 2}\) (10) rings propagated in the direction of the a axis, and relatively strong π(triazolyl)···π(triazolyl) and (iii) π(phenyl)···π(phenyl) interactions.in which the Cg···Cg distances and perpendicular distances between planes through the phenyltriazole fragments, in both cases are 3.865(4) and 3.436(4) Å, respectively.

The position of the aldehyde group on C5 of the triazole ring in 1f, results in a much larger dihedral angle between the triazoleyland aryl planes of 62.34(5)°, compared to those in 2a and 1e. Again the carbonyl oxygen is involved in C–H···O hydrogen bonds, this time with a CH unit in the trimethylsilyl group: these C–H···O hydrogen bonds produce chains of molecules.

Comparison of the structure of 2a can be made with the hemihydrate of 1-(3-C6H4)-4-HOCH2-1H-1,2,3-triazole, 1g, [39], 1-(3,5-dimethylphenyl)-4-HOCH2-1H-1,2,3-triazole, 1 h, [40] and 1-(4-biphenyl)-4-HOCH2-1H-1,2,3-triazole. 1i [40] and 1-(4-HO2CC6H4-4-HOCH2-1H-1,2,3-triazole. 1j [41], 1-(2-HO2CC6H4-4-HOCH2-1H-1,2,3-triazole. 1k [41] and 1-(2-HOC6H4-4-HOCH2-1H-1,2,3-triazole. 1l [41].

In both 1-(4-biphenyl)-4-HOCH2-1H-1,2,3-triazole, 1i, and 1-(3,5-dimethylphenyl)-4-HOCH2-1H-1,2,3-triazole, 1h, [40], there are O–H···N3 hydrogen bonds involving the hydroxyl group. However in 1i, these generate chains of molecules, while in 1h centrosymmetric dimers, having \({\text{R}}^{ 2}_{ 2}\) (10) rings, are formed. The dihedral angles between the triazolyl and phenyl rings are 25.29(5) and 23.71(5)° in 1i and 1h, respectively, and thus are much larger than that in 2b [2.44°] and must be a consequence of the crystal packing rather than any steric effect arising from the substituents. Neither 1i nor 1h exhibits π···π stacking interactions.

In the hemihydrate of 1-(3-ClC6H4)-4-HOCH2-1H-1,2,3-triazole, [1g.0.5(H 2 O)] [39], the hydrate plays a significant role in the supramolecular array. The most important intermolecular interactions in [1g.0.5(H 2 O] are Ow–Hw···N3 and Ow–Hw···Ow hydrogen bonds, which generate chains of molecules of water and 1g propagated in the direction of the a-axis. Additional features of the structure are O6H6 twelve-membered rings formed from O–H···O hydrogen bonds involving two hydrate molecules and the hydroxyl groups of two molecules each of the two independent molecules of 1g. Also present in [(1g)2(H2O)] are weak π(phenyl)···π(phenyl) interactions.

As illustrated by [1g.0.5(H 2 O)], the presence of additional donor centres radically changes the involvement of the triazole bound hydroxyl group. This is also very clearly illustrated by the group of compounds, 1j–1l [26], in which the hydroxyl group on the triazole ring preferentially links with the hydroxyl or carboxylic acid substituents on the phenyl ring, leading to the formation of helices and other supramolecular architectures.

Conclusion

There appears to be no consistent intermolecular interaction, nor dihedral angle between the aryl and triazole rings, in either of the two series of aryl-1,2,3-triazoles . The dependence of the supramolecular array on the substituent(s) is clearly apparent.

Experimental

The compounds, 1a, 2a and 2b, were prepared as reported [23]. For the structure determinations, crystals of 1a were obtained from MeOH, 2a from EtOH and 2b from Me2CO solutions.

X-Ray Crystallography

Data for compounds 1a and 2b were obtained at 120(2) K while data for compound 2a were collected at 100(2) K, all with Mo-Kα radiation by means of a Bruker–Nonius Roper CCD camera on kappa-goniostat instrument of the NCS crystallographic service, based at the University of Southampton. Data collection, data reduction and unit cell refinement were achieved with DENZO [41] and COLLECT [42] programs. Correction for absorption was achieved in each program SADABS 2007/2 [43]. The program MERCURY [44] was used in the preparation of the Figures. SHELXL97 [45] and PLATON [46] were used in the calculation of molecular geometry. The structures were solved by direct methods using SHELXS-97 [45] and fully refined by means of the program SHELXL-97 [45]. Difference map provided position for the aldehydic hydrogen atoms of 2b. All other hydrogen atoms were placed in calculated positions. Crystal data and structure refinement details are listed in Table 5.

Table 5 Crystal data and structure refinement
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Supplementary Material

Full details of the crystal structure determinations in cif format are available in the online version, at doi: (to be inserted), and have also been deposited with the Cambridge Crystallographic Data Centre with deposition numbers, 1417606, 1417783 and 1417607, respectively for 1a, 2a and 2b. Copies of these can be obtained free of charge on written application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax: +44 1223 336033); on request by e-mail to deposit@ccdc.cam.ac.uk or by access to http://www.ccdc.cam.ac.uk.