1,2,3-Triazoles represent an important class of heterocyclic compounds with a broad spectrum of biological effects, including anti-inflammatory, antimicrobial, tuberculostatic, antiplatelet, and antiviral activity.1 Reports have been published in recent years on the use of 1,2,3-triazoles in the design of liquid crystals,2 a metallo-supramolecular gels for the restoration of metallic coatings,2 b and thermally stable materials for organic lightemitting devices.2 c

One of the most effective methods for the preparation of 1,2,3-triazoles is based on 1,3-dipolar cycloaddition of sodium azide at the activated double bond of conjugated nitroalkenes with elimination of the nitro group.3 The availability and diversity of the starting nitroalkenes, as well as the simplicity of isolation and high yields of the target products correspond to the basic principles of the modern concept of click chemistry.4 The reaction is usually performed by moderate heating in DMSO or DMF, using an excess of the reagent (1.5–2.0 equiv). At the same time, the interaction of β-nitrostyrenes with NaN3 is often accompanied by dimerization or trimerization of the nitroalkene in the presence of azide anion, leading to the formation of 4-aryl-5-(1-aryl-2-nitroethyl)-1H-1,2,3-triazoles and 1,3,5-triarylbenzenes as by-products.3 c,d The addition of small amounts of p-toluenesulfonic acid (0.1–0.5 equiv) to the reaction mixture allowed to completely suppress these side reactions.3 e

It has been recently shown5 a that 2-unsubstituted 3-nitro-2H-chromenes 1 containing β-nitrostyrene moiety in their molecules interacted with sodium azide in DMSO or DMF at 160°C under the conditions of microwave heating, forming chromeno[3,4-d]triazoles 2 in 63–89% yields. An analogous reaction involving 2-aryl-3-nitro-2H-chromenes 3 (DMSO, 80°C, 25–90 min) gave 61–82% yields of 4-arylsubstituted chromenotriazoles 4 (Scheme 1).5 b The sterically hindered 2,2-dimethyl-3-nitro-2H-chromene was found to be less active and reacted with sodium azide under the same conditions over 3 h, forming the respective triazole in 58% yield, while 3-nitro-2,2-diphenyl-2H-chromene did not participate in a cycloaddition reaction at all.5 b

scheme 1

Scheme 1.

It should be noted that products 2 and 4 represent chromene derivatives annulated with triazole ring, while chromene also forms the structural framework of many natural and synthetic compounds with valuable biological and pharmacological properties.6

In a continuation of our studies aimed at the development of methods for Δ3-annulation of 3-nitro-2-(trifluoro(trichloro)methyl)-2H-chromenes 5 with a carbo- or heterocycle,7 in the current work we investigated the reaction of chromenes 5 and 3-nitro-2-phenyl-2-(trifluoromethyl)-2H-chromenes 6, representing hybrid structures of chromenes 3 and 5 (Fig. 1), with sodium azide under various conditions. This method may be useful for the preparation of chromeno[3,4-d]triazoles containing a trihalomethyl group at position 4.

Figure 1.
figure 1

2-(Trihalomethyl)-substituted 3-nitro-2Н-chromenes 5 and 6.

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For the purpose of optimizing the reaction conditions, in the first step we studied the reaction with 2-CF3-nitrochromene 5a lacking any substituents at the benzene ring, which led to the formation of 4-(trifluoromethyl)-2,4-dihydrochromeno[3,4-d][1,2,3]triazole (7a). The highest yields of compound 7a were observed when performing the process in DMSO or DMF at 60°C for 10 min (control by TLC) in the presence of 0.5 equiv of p-toluenesulfonic acid (TsOH) (Scheme 2, Table 1). The role of TsOH in this reaction was not entirely clear, but was probably linked to the additional activation of double bond in the starting chromene via protonation of oxygen atom in the nitro group.

scheme 2

Scheme 2.

Table 1. Optimization of conditions for the reaction of chromene 5a with NaN3
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The optimized reaction conditions allowed to obtain high yields of 4-CF3-chromenotriazoles 7b–h containing electron-donating or electron-withdrawing substituents in the aromatic ring (Scheme 3, Table 2). In the case of the more active 6-mono- and 6,8-dihalo-substituted chromenes 5e–h, the reactions both in DMSO and in DMF were complete after 5 min. It should be noted that chromenotriazoles 7a–h were isolated from the reaction mixture by simple filtration as pure samples that were suitable for analysis, and did not require additional purification by recrystallization or column chromatography. As shown in Table 2, the yields of products 7a–h practically did not depend on the electron-donating or electron-withdrawing properties of the substituent R in the aromatic ring.

scheme 3

Scheme 3.

Table 2. Reaction conditions and yields of 4-CF3-chromenotriazoles 7b–h
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2-(Trichloromethyl)-substituted nitrochromenes 5i–p under analogous conditions formed the respective triazoles 7i–p in 37–64% yields. The more active chromenes 5m–p reacted with sodium azide over 10–25 min, while the reactions with chromene 5i lacking substituents in the benzene ring and chromenes 5j–l containing electrondonating substituents in the aromatic ring were complete in only 1–1.5 h and were accompanied by noticeable resinification (Scheme 4, Table 3). Similarly to the case of 4-(trifluoromethyl)-substituted triazoles 7a–h, the target products 7i–p were isolated from reaction mixtures by filtration and the impurities were removed by washing with a small amount of hexane–CH2Cl2 mixture.

scheme 4

Scheme 4.

Table 3. Reaction conditions and yields of 4-(trichloromethyl)-substituted chromenotriazoles 7i–p
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The lower yields of chromenotriazoles 7i–p compared to 4-trifluoromethyl analogs 7a–h were caused by the formation of 4-(dichloromethylidene)chromeno[3,4-d]triazoles 9i–p as by-products upon elimination of HCl molecule from triazoles 7i–p in the presence of basic azide and nitrite anions. We can not exclude the possibility that compounds 9i–p were formed as a result of HCl elimination from 2-(trichloromethyl)nitrochromenes 5i–p, followed by addition of sodium azide to the intermediates, 4-(dichloromethylidene)chromenes 8i–p. This process can be accompanied by partial resinification of the unstable nitrochromenes 8i–p (Scheme 5).

scheme 5

Scheme 5.

Indeed, the reaction of 6,8-dibromo-3-nitro-2-(trichloromethyl)-2H-chromene (5p) with NaN3 in DMSO allowed to isolate a mixture of products 7p and 9p in 4:1 ratio. Despite the fact that triazole 9p could not be isolated as analytically pure sample, its structure was proved with 1H NMR spectroscopy by analysis using chromatography coupled to high-resolution mass spectrometry. Mixtures with similar composition were formed also in reactions involving 2-(trichloromethyl)chromenes 5i–o. Elimination of HCl by the action of nitrite anion in DMSO or DMF has been previously observed in the series of 2,2-diaryl-1,1,1-trichloroethanes.8

IR spectra of chromenotriazoles 7a–p showed a strong absorption band due to ν(NH) stretching vibrations in the range of 3278–2469 cm−1. 1H NMR spectra recorded in DMSO-d 6 solution contained a characteristic quartet (compounds 7a–h) or singlet (compounds 7i–p) of the 4-CH proton in the narrow range of 6.49−6.94 ppm and the triazole NH proton signal as a broadened singlet at 15.51–15.95 ppm. The signal of trifluoromethyl group linked to sp 3-hybridized carbon atom was manifested in 19F NMR spectra of 2-(trifluoromethyl)chromenotriazoles 7a–h at 84.5–84.9 ppm as a broadened singlet or doublet with 3 J FH = 6.5–6.8 Hz. 13C NMR spectra of compounds 7a–e,g featured quartets of the CF3 group and the С-4 carbon atom in the range of 122.4–122.9 and 70.4–71.4 ppm, respectively, with spin-spin coupling constants 1 J CF = 284.2–284.8 and 2 J CF = 33.6–34.4 Hz.

The structure of chromenotriazole 7d was proved by X-ray structural analysis (Fig. 2). As shown in Figure 2, the hydrogen atom of triazole ring in this crystal structure was located at the N(2) nitrogen atom.

Figure 2.
figure 2

The molecular structure of compound 7d with atoms represented by thermal vibration ellipsoids of 50% probability.

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The sterically hindered 2,2-disubstituted nitrochromenes 6a–f were found to be less active than the respective 2-(trifluoromethyl)nitrochromenes 5a–h and reacted with sodium azide at 70°C over 10–90 min, forming 4-phenyl-4-(trifluoromethyl)chromeno[3,4-d]triazoles 10a–f in 60–78% yields (Scheme 6, Table 4). Products 10a–f were isolated from reaction mixture by filtration and impurities were removed by recrystallization from CH2Cl2–hexane system. It should be emphasized that the presence of an electron-withdrawing trifluoromethyl group was the reason for the considerably higher reactivity of compounds 6a–f compared to 3-nitro-2,2-diphenyl-2H-chromene, which did not react with sodium azide under these conditions.5 b

scheme 6

Scheme 6.

Table 4. Reaction conditions and yields of 4-CF3-4-Ph-chromenotriazoles 10a–f
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IR spectra of chromenotriazoles 10a–f showed a ν(NH) vibration band in the range of 3290–3114 cm−1. The broadened singlet of triazole NH proton appeared at 11.92–12.12 ppm in 1H NMR spectra acquired in CDCl3 solution (compounds 10a,d–f) or at ~15.8 ppm in DMSO-d 6 solution (compounds 10b,c). 19F NMR spectra of compounds 10a–f featured a singlet of trifluoromethyl group at 83.5–83.9 ppm in CDCl3 solution or at 85.6–85.7 ppm in DMSO-d 6 solution. 13C NMR spectra of triazoles 10a,b,e,f contained characteristic quartets of the CF3 group and the С-4 carbon atom with spin-spin coupling constants 1 J CF = 284.7–285.5 and 2 J CF = 30.8–32.7 Hz.

The structure of chromenotriazole 10d was confirmed by X-ray structural analysis (Fig. 3). Similarly to triazole 7d, the triazole ring hydrogen atom in the molecule of compound 10d in crystal structure was located at the N(2) nitrogen atom.

Figure 3.
figure 3

The molecular structure of compound 10d with atoms represented by thermal vibration ellipsoids of 50% probability.

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Thus, 3-nitro-2-(trifluoromethyl)-2H-chromenes were significantly more reactive toward sodium azide compared to 2-aryl-3-nitro-2H-chromenes, while 3-nitro-2-phenyl-2-(trifluoromethyl)-2H-chromenes were found to be more reactive than their 2,2-dimethyl- and 2,2-diphenylsubstituted analogs. In the case of 2-(trichloromethyl)nitrochromenes, the cycloaddition was accompanied by partial elimination of HCl. Our developed method for the preparation of 4-(trihalomethyl)-substituted chromeno[3,4-d]-triazoles was sufficiently simple, and the synthesized products clearly are of interest for researchers in the fields of medicinal chemistry and materials science.

Experimental

IR spectra were recorded on a Bruker Alpha spectrometer with ZnSe ATR accessory. 1Н and 19F NMR spectra were acquired on Bruker DRX-400 (400 and 376 MHz, respectively, compounds 5g,o, 7a–f,h,k,o, 10e,f) and Bruker Avance 500 (500 and 471 MHz, respectively, the rest of the compounds) spectrometers. The solvents were CDCl3 (compounds 5g,o, 10a,d–f) or DMSO-d 6 (the rest of the compounds). The internal standards were TMS (for 1Н nuclei) and C6F6 (for 19F nuclei). 13C NMR spectra were acquired on a Bruker Avance-500 spectrometer (126 MHz) in CDCl3 solution (compounds 5g,o, 10a,e,f) or DMSO-d 6 solution (the rest of the compounds), with solvent signals as internal standard (77.0 ppm for CDCl3, 39.5 ppm for DMSO-d 6). High-resolution mass spectra (electrospray ionization) were obtained on a Waters Xevo QT of instrument. Elemental analysis was performed on a PerkinElmer 2400 automatic analyzer. Melting points were determined on a Stuart SMP40 apparatus. The reaction progress and purity of the obtained compounds were controlled by TLC on Sorbfil PTSKh-AF-A-UF plates. The starting nitrochromenes 5a–p and 6a–f were obtained according to published procedures.9 , 10

6,8-Dichloro-3-nitro-2-(trifluoromethyl)-2 H -chromene (5g). Yield 65%, yellow powder, mp 111–112°C (EtOH). IR spectrum, ν, cm−1: 1650, 1561, 1524, 1451, 1435, 1361, 1330. 1H NMR spectrum, δ, ppm (J, Hz): 6.19 (1H, q, J = 6.1, 2-СH); 7.29 (1H, d, J = 2.2, H-5(7)); 7.50 (1H, d, J = 2.2, H-7(5)); 8.03 (1H, s, 4-СH). 13C NMR spectrum, δ, ppm (J, Hz): 70.1 (q, J = 34.9, C-2); 118.8; 122.3 (q, J = 287.9, CF3); 123.2; 128.5; 128.7; 130.8; 134.5; 135.3; 147.5. 19F NMR spectrum, δ, ppm (J, Hz): 83.9 (d, J = 6.1, CF3). Found, %: С 38.22; Н 1.26; N 4.46. C10H4Cl2F3NO3. Calculated, %: С 38.25; Н 1.28; N 4.46.

6,8-Dichloro-3-nitro-2-(trichloromethyl)-2 H -chromene (5o). Yield 54%, yellow powder, mp 146–147°C (EtOH). IR spectrum, ν, cm−1: 1642, 1558, 1552, 1447, 1434, 1418, 1327. 1H NMR spectrum, δ, ppm (J, Hz): 6.40 (1H, s, 2-СH); 7.27 (1H, d, J = 2.4, H-5(7)); 7.50 (1H, d, J = 2.4, H-7(5)); 8.02 (1H, s, 4-СH). 13C NMR spectrum, δ, ppm: 80.2; 98.2; 119.5; 123.0; 127.9; 128.3; 130.8; 134.3; 138.0; 148.0. Found, %: С 33.24; Н 0.97; N 3.85. C10H4Cl5NO3. Calculated, %: С 33.05; Н 1.11; N 3.85.

Synthesis of chromeno[3,4- d ]triazoles 7a–p (General method). A solution of nitrochromene 5a–p (1.0 mmol), NaN3 (130 mg, 2.0 mmol), and TsOH (86 mg, 0.5 mmol) in DMSO or DMF (3 ml) was stirred at 60°C for the duration indicated in Tables 1–3. The reaction mixture was then cooled to room temperature and poured into H2O (20 ml). In order to completely precipitate 4-(trichloromethyl)-triazoles 7i–p, saturated aqueous NaCl solution (1.0 ml) was added to the reaction mixture. The precipitate that formed was filtered off, washed with water (3×10 ml), and dried at 60°C. In the case of 4-(trichloromethyl)chromenotriazoles 7i–p, the product was dried and washed with a small amount of 1:2 CH2Cl2−hexane mixture (3×0.5 ml) for the purpose of removing impurities.

4-(Trifluoromethyl)-2,4-dihydrochromeno[3,4- d ][1,2,3]-triazole (7a). Yield 89% (DMSO), 86% (DMF), white powder, mp 193–194°C. IR spectrum, ν, cm−1: 2469, 1645, 1493, 1452, 1423, 1353, 1302. 1H NMR spectrum, δ, ppm (J, Hz): 6.68 (1H, q, J = 6.8, 4-CH); 7.12−7.19 (2H, m, H-6,8); 7.38 (1H, td, J = 7.9, J = 1.3, H-7); 7.71 (1H, d, 7.2, H 9); 15.61 (1H, br. s, NH). 13C NMR spectrum, δ, ppm (J, Hz): 70.7 (q, J = 33.9, C-4); 114.1 (br. s); 116.8; 122.8; 122.9 (q, J = 284.3, CF3); 123.2; 130.6; 132.4 (br. s); 136.7 (br. s); 151.4. 19F NMR spectrum, δ, ppm: 84.8 (br. s, CF3). Found, m/z: 242.0535 [М+Н]+. С10Н7F3N3O. Calculated, m/z: 242.0536.

8-Methyl-4-(trifluoromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (7b). Yield 90% (DMSO), 84% (DMF), light-yellow powder, mp 171–172°C. IR spectrum, ν, cm−1: 3146, 1630, 1542, 1505, 1470, 1353, 1316. 1H NMR spectrum, δ, ppm (J, Hz): 2.31 (3H, s, CH3); 6.62 (1H, q, J = 6.8, 4-CH); 7.03 (1H, d, J = 8.3, H-6); 7.15 (1H, dd, J = 8.3, J = 1.4, H-7); 7.52 (1H, br. s, H-9); 15.54 (1H, br. s, NH). 13C NMR spectrum, δ, ppm (J, Hz): 20.1; 70.6 (q, J = 33.7, C-4); 113.8 (br. s); 116.6; 122.9 (q, J = 284.7, CF3); 123.0; 131.1; 132.2; 132.6 (br. s); 137.2 (br. s); 149.3. 19F NMR spectrum, δ, ppm: 84.9 (br. s, CF3). Found, m/z: 256.0697 [М+Н]+. С11Н9F3N3O. Calculated, m/z: 256.0692.

8-Methoxy-4-(trifluoromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (7c). Yield 93% (DMSO), 85% (DMF), mp 200–201°C. IR spectrum, ν, cm−1: 3150, 1603, 1515, 1505, 1476, 1441, 1350. 1H NMR spectrum, δ, ppm (J, Hz): 3.79 (3H, s, OCH3); 6.59 (1H, q, J = 6.9, 4-CH); 6.92 (1H, dd, J = 9.0, J = 3.0, H-7); 7.09 (1H, d, J = 9.0, H-6); 7.23 (1H, d, J = 3.0, H-9); 15.65 (1H, br. s, NH). 13C NMR spectrum, δ, ppm (J, Hz): 55.5; 70.4 (q, J = 33.6, C-4); 107.0; 114.6 (br. s); 116.4; 117.9; 122.9 (q, J = 284.8, CF3); 132.9 (br. s); 137.0 (br. s); 145.2; 154.8. 19F NMR spectrum, δ, ppm: 84.9 (br. s, CF3). Found, m/z: 272.0643 [М+Н]+. С11Н9F3N3O2. Calculated, m/z: 272.0641.

6-Ethoxy-4-(trifluoromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (7d). Yield 87% (DMSO), 86% (DMF), mp 159–160°C. IR spectrum, ν, cm−1: 3278, 1591, 1548, 1461, 1391, 1356, 1301. 1H NMR spectrum, δ, ppm (J, Hz): 1.34 (3H, t, J = 7.0, OCH2CH3); 4.08 (1H, dq, J = 9.7, J = 7.0) and 4.11 (1H, dq, J = 9.7, J = 7.0, OCH2CH3); 6.69 (1H, q, J = 6.8, 4-CH); 7.03−7.13 (2H, m, H-7,9); 7.22−7.35 (1H, m, H-8); 15.54 (1H, br. s, NH). 13C NMR spectrum, δ, ppm (J, Hz): 14.6; 64.4; 70.4 (q, J = 33.9, C-4); 114.5; 115.0 (br. s); 115.4; 122.8 (q, J = 284.6, CF3); 123.0; 132.6 (br. s); 137.8 (br. s); 140.8; 147.5. 19F NMR spectrum, δ, ppm: 84.8 (br. s, CF3). Found, m/z: 286.0801 [М+H]+. С12Н11F3N3O2. Calculated, m/z: 286.0798.

8-Chloro-4-(trifluoromethyl)-2,4-dihydrochromeno[3,4- d ]-[1,2,3]triazole (7e). Yield 88% (DMSO), 90% (DMF), white powder, mp 180–181°C. IR spectrum, ν, cm−1: 3213, 1480, 1459, 1443, 1399, 1362, 1325. 1H NMR spectrum, δ, ppm (J, Hz): 6.74 (1H, q, J = 6.8, 4-CH); 7.20 (1H, d, J = 8.8, H-6); 7.40 (1H, dd, J = 8.8, J = 2.6, H-7); 7.72 (1H, d, J = 2.6, H-9); 15.73 (1H, br. s, NH). 13C NMR spectrum, δ, ppm (J, Hz): 70.9 (q, J = 34.0, C-4); 115.8 (br. s); 118.8; 122.1; 122.7 (q, J = 284.3, CF3); 127.0; 130.1; 132.6 (br. s); 135.9 (br. s); 150.0. 19F NMR spectrum, δ, ppm: 84.8 (br. s, CF3). Found, m/z: 297.9964 [М+Na]+. С10Н5ClF3N3NaO. Calculated, m/z: 297.9965.

8-Bromo-4-(trifluoromethyl)-2,4-dihydrochromeno[3,4- d ]-[1,2,3]triazole (7f). Yield 86% (DMSO), 84% (DMF), white powder, mp 183–184°C. IR spectrum, ν, cm−1: 3206, 1482, 1460, 1437, 1396, 1358, 1316. 1H NMR spectrum, δ, ppm (J, Hz): 6.75 (1H, q, J = 6.8, 4-CH); 7.15 (1H, d, J = 8.8, H-6); 7.53 (1H, dd, J = 8.8, J = 2.4, H-7); 7.84 (1H, d, J = 2.4, H-9); 15.82 (1H, br. s, NH). 19F NMR spectrum, δ, ppm (J, Hz): 84.8 (d, J = 6.8, CF3). Found, m/z: 341.9458 [М+Na]+. С10Н5BrF3N3NaO. Calculated, m/z: 341.9460.

6,8-Dichloro-4-(trifluoromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (7g). Yield 96% (DMSO), 85% (DMF), white powder, mp 149–150°C. IR spectrum, ν, cm−1: 3148, 1494, 1442, 1428, 1396, 1376, 1352, 1309. 1H NMR spectrum, δ, ppm (J, Hz): 6.94 (1H, q, J = 6.7, 4-CH); 7.71 (1H, d, J = 2.5, H-7(9)); 7.73 (1H, d, J = 2.5, H-9(7)); 15.95 (1H, br. s, NH). 13C NMR spectrum, δ, ppm (J, Hz): 71.4 (q, J = 34.4, C-4); 117.2 (br. s); 121.1; 122.3; 122.4 (q, J = 284.2, CF3); 127.2; 129.9; 132.7 (br. s); 135.6 (br. s); 145.9. 19F NMR spectrum, δ, ppm (J, Hz): 84.8 (d, J = 6.7, CF3). Found, m/z: 309.9752 [М+Н]+. С10Н5Cl2F3N3O. Calculated, m/z: 309.9756.

6,8-Dibromo-4-(trifluoromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (7h). Yield 87% (DMSO), 88% (DMF), white powder, mp 186–187°C. IR spectrum, ν, cm−1: 3150, 1490, 1435, 1408, 1350, 1305. 1H NMR spectrum, δ, ppm (J, Hz): 6.93 (1H, q, J = 6.5, 4-CH); 7.87 (1H, d, J = 2.1, H-7(9)); 7.90 (1H, d, J = 2.1, H-9(7)); 15.94 (1H, br. s, NH). 19F NMR spectrum, δ, ppm (J, Hz): 84.5 (d, J = 6.5, CF3). Found, m/z: 399.8725 [М+Н]+. С10Н5Br2F3N3O. Calculated, m/z: 399.8726.

4-(Trichloromethyl)-2,4-dihydrochromeno[3,4- d ][1,2,3]-triazole (7i). Yield 50% (DMSO), 49% (DMF), light-yellow powder, mp 212–213°C (decomp.). IR spectrum, ν, cm−1: 3185, 1624, 1590, 1479, 1446, 1332. 1H NMR spectrum, δ, ppm (J, Hz): 6.58 (1H, s, 4-CH); 7.09−7.17 (2H, m, H-6,8); 7.34 (1H, td, J = 7.9, J = 1.3, H-7); 7.72 (1H, d, J = 7.1, H-9); 15.54 (1H, br. s, NH). 13C NMR spectrum, δ, ppm: 81.5; 99.8; 114.6 (br. s); 116.6; 122.6; 122.7; 130.4; 134.7 (br. s); 138.6 (br. s); 152.1. Found, m/z: 311.9468 [М+Na]+. С10Н6Cl3N3NaO. Calculated, m/z: 311.9469.

8-Methyl-4-(trichloromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (7j). Yield 49% (DMSO), 45% (DMF), light-yellow powder, mp 195–196°C (decomp.). IR spectrum, ν, cm−1: 3135, 1644, 1523, 1470, 1321. 1H NMR spectrum, δ, ppm (J, Hz): 2.30 (3H, s, CH3); 6.52 (1H, s, 4-CH); 7.03 (1H, d, J = 8.3, H-6); 7.15 (1H, br. d, J = 8.3, H-7); 7.53 (1H, br. s, H-9); 15.51 (1H, br. s, NH). 13C NMR spectrum, δ, ppm: 20.2; 81.4; 99.9; 114.1 (br. s); 116.4; 122.7; 131.0; 131.7; 134.4 (br. s); 138.2 (br. s); 149.9. Found, m/z: 303.9805 [М+Н]+. С11Н9Cl3N3O. Calculated, m/z: 303.9806.

8-Methoxy-4-(trichloromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (7k). Yield 47% (DMSO), 41% (DMF), beige powder, mp 145–146°C (decomp.). IR spectrum, ν, cm−1: 3156, 1530, 1494, 1464, 1439, 1414. 1H NMR spectrum, δ, ppm (J, Hz): 3.78 (3H, s, OCH3); 6.49 (1H, s, 4-CH); 6.92 (1H, br. d, J = 8.0, H-7); 7.07 (1H, d, J = 8.0, H-6); 7.23 (1H, br. s, H-9); 15.55 (1H, br. s, NH). Found, m/z: 319.9757 [М+Н]+. С11Н9Cl3N3O2. Calculated, m/z: 319.9755.

8-Ethoxy-4-(trichloromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (7l). Yield 43% (DMSO), 37% (DMF), beige powder, mp 133–134°C (decomp.). IR spectrum, ν, cm−1: 3202, 1592, 1528, 1454, 1433, 1389. 1H NMR spectrum, δ, ppm (J, Hz): 3.30 (3H, t, J = 6.9, OCH2CH3); 4.11 (2H, br. q, J = 6.9, OCH 2CH 3); 6.59 (1H, s, 4-CH); 6.99−7.36 (3H, m, H Ar); 15.51 (1H, br. s, NH). Found, m/z: 333.9913 [М+Н]+. С12Н11Cl3N3O2. Calculated, m/z: 333.9911.

8-Chloro-4-(trichloromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (7m). Yield 51% (DMSO), 50% (DMF), light-yellow powder, mp 204–205°C (decomp.). IR spectrum, ν, cm−1: 3219, 1476, 1453, 1434, 1396. 1H NMR spectrum, δ, ppm (J, Hz): 6.65 (1H, s, 4-CH); 7.19 (1H, d, J = 8.8, H-6); 7.40 (1H, dd, J = 8.8, J = 2.6, H-7); 7.72 (1H, d, J = 2.6, H-9); 15.72 (1H, br. s, NH). 13C NMR spectrum, δ, ppm: 81.5; 99.4; 116.0 (br. s); 118.5; 121.9; 126.5; 130.1; 134.5 (br. s); 137.5 (br. s); 150.7. Found, m/z: 347.9047 [М+Na]+. С10Н5Cl4N3NaO. Calculated, m/z: 347.9049.

8-Bromo-4-(trichloromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (7n). Yield 59% (DMSO), 58% (DMF), light-yellow powder, mp 219–220°C (decomp.). IR spectrum, ν, cm−1: 3114, 2876, 1493, 1462, 1454, 1430, 1398, 1380, 1349, 1326. 1H NMR spectrum, δ, ppm (J, Hz): 6.65 (1H, s, 4-CH); 7.13 (1H, d, J = 8.7, H-6); 7.52 (1H, br. d, J = 8.7, H-7); 7.84 (1H, br. s, H-9); 15.76 (1H, br. s, NH). Found, m/z: 369.8733 [М+Н]+. С10Н6BrCl3N3O. Calculated, m/z: 369.8734.

6,8-Dichloro-4-(trichloromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (7o). Yield 56% (DMSO), 56% (DMF), light-yellow powder, mp 114–115°C (decomp.). IR spectrum, ν, cm−1: 3152, 1524, 1487, 1440, 1426, 1394. 1H NMR spectrum, δ, ppm (J, Hz): 6.82 (1H, s, 4-CH); 7.68 (1H, d, J = 2.1, H-7(9)); 7.74 (1H, d, J = 2.1, H-9(7)); 15.93 (1H, br. s, NH). Found, m/z: 357.8865 [М+Н]+. С10Н5Cl5N3O. Calculated, m/z: 357.8870.

6,8-Dibromo-4-(trichloromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (7p). Yield 63% (DMSO), 64% (DMF), pink powder, mp 124–125°C (decomp.). IR spectrum, ν, cm−1: 3149, 1519, 1486, 1432, 1388, 1369. 1H NMR spectrum, δ, ppm (J, Hz): 6.83 (1H, s, 4-CH); 7.87 (1H, d, J = 2.3, H-7(9)); 7.90 (1H, d, J = 2.3, H-9(7)); 15.92 (1H, br. s, NH). 13C NMR spectrum, δ, ppm: 82.0; 99.0; 111.4; 114.6; 117.7 (br. s); 124.1 (2C); 135.2; 148.1 (One C signal was not observed). Found, m/z: 445.7861 [М+Н]+. С10Н5Br2Cl3N3O. Calculated, m/z: 445.7859.

6,8-Dibromo-4-(dichloromethylidene)-2,4-dihydrochromeno[3,4- d ][1,2,3]triazole (9p) was obtained as a mixture with triazole 7p. 1H NMR spectrum, δ, ppm (J, Hz): 7.92 (1H, d, J = 2.2, H-7(9)); 7.98 (1H, br. d, J = 2.2, H-9(7)); 16.05 (1H, br. s, NH). Found, m/z: 409.8093 [М+Н]+. С10Н4Br2Cl2N3O. Calculated, m/z: 409.8093.

Synthesis of chromeno[3,4- d ]triazoles 10a–f (General method). A solution of the appropriate nitrochromene 6a–f (1.0 mmol), NaN3 (0.13 g, 2.0 mmol), and TsOH (86 mg, 0.5 mmol) in DMSO or DMF (3 ml) was stirred at 70°C for the duration indicated in Table 4. The reaction mixture was then cooled to room temperature and poured into H2O (20 ml). The precipitate that formed was filtered off and recrystallized from a 1:2 mixture of CH2Cl2–hexane. Compounds 10a,e were extracted with EtOAc (3×10 ml), the solvent was removed at reduced pressure, and the residue was purified by silica gel column chromatography, using CHCl3 as eluent. Triazoles 10a–f were obtained as white powders.

4-Phenyl-4-(trifluoromethyl)-2,4-dihydrochromeno-[3,4- d ][1,2,3]triazole (10a). Yield 73% (DMSO), 76% (DMF), mp 146–147°C. IR spectrum, ν, cm−1: 3289, 1622, 1472, 1450, 1426, 1312. 1H NMR spectrum, δ, ppm (J, Hz): 7.10 (1H, td, J = 7.5, J = 1.1, H-7); 7.28 (1H, dd, J = 8.3, J = 0.8, H-6); 7.33−7.41 (4H, m, H-8, H-3,4,5 Ph); 7.73−7.78 (3H, m, H-9, H-2,6 Ph); 12.12 (1H, br. s, NH). 13C NMR spectrum, δ, ppm (J, Hz): 81.2 (q, J = 32.1, C-4); 114.6; 117.9; 123.1 (q, J = 285.5, CF3); 123.3; 123.4; 127.2; 128.4; 129.5; 131.0; 134.1; 138.3; 139.3 (br. s); 151.6. 19F NMR spectrum, δ, ppm: 83.7 (s, CF3). Found, m/z: 318.0851 [М+Н]+. С16Н11F3N3O. Calculated, m/z: 318.0849.

8-Methyl-4-phenyl-4-(trifluoromethyl)-2,4-dihydrochromeno[3,4- d ][1,2,3]triazole (10b). Yield 63% (DMSO), 60% (DMF), mp 174–175°C. IR spectrum, ν, cm−1: 3147, 3031, 1500, 1465, 1449. 1H NMR spectrum, δ, ppm (J, Hz): 2.28 (3H, s, CH3); 7.20 (1H, br. d, J = 8.3, H-7); 7.30 (1H, d, J = 8.3, H-6); 7.37–7.53 (4H, m, H-9, H-3,4,5 Ph); 7.65 (2H, d, J = 6.1, H-2,6 Ph); 15.76 (1H, br. s, NH). 13C NMR spectrum, δ, ppm (J, Hz): 20.1; 80.7 (q, J = 30.8, C-4); 114.4 (br. s); 117.7; 122.9; 123.1 (q, J = 284.7, CF3); 126.9; 128.6; 129.7; 131.2; 132.8; 133.7; 136.7 (br. s); 137.4 (br. s); 148.1. 19F NMR spectrum, δ, ppm: 85.6 (s, CF3). Found, m/z: 332.1006 [М+Н]+. С17Н13F3N3O. Calculated, m/z: 332.1005.

8-Methoxy-4-phenyl-4-(trifluoromethyl)-2,4-dihydrochromeno[ 3,4- d ][1,2,3]triazole (10c). Yield 78% (DMSO), 75% (DMF), mp 147–148°C. IR spectrum, ν, cm−1: 3148, 3040, 1536, 1497, 1467, 1439, 1415, 1324. 1H NMR spectrum, δ, ppm (J, Hz): 3.76 (3H, s, OCH3); 6.96 (1H, br. d, J = 8.7, H-7); 7.18 (1H, br. s, H-9); 7.36 (1H, d, J = 8.7, H-6); 7.38–7.51 (3H, m, H-3,4,5 Ph); 7.64 (2H, d, J = 6.4, H-2,6 Ph); 15.81 (1H, br. s, NH). 19F NMR spectrum, δ, ppm: 85.7 (s, CF3). Found, m/z: 348.0958 [М+Н]+. С17Н13F3N3O2. Calculated, m/z: 348.0954.

6-Ethoxy-4-phenyl-4-(trifluoromethyl)-2,4-dihydrochromeno[3,4- d ][1,2,3]triazole (10d). Yield 74% (DMSO), 70% (DMF), mp 144–145°C. IR spectrum, ν, cm−1: 3265, 1591, 1524, 1464, 1447, 1305. 1H NMR spectrum, δ, ppm (J, Hz): 1.55 (3H, t, J = 7.0, OCH2CH3); 4.19 (1H, dq, J = 9.1, J = 7.0) and 4.25 (1H, dq, J = 9.1, J = 7.0, OCH2CH3); 6.95 (1H, dd, J = 8.2, J = 1.2, H-7); 7.01 (1H, t, J = 7.9, H-8); 7.32 (1H, dd, J = 7.6, J = 1.2, H-9); 7.33–7.39 (3H, m, H-3,4,5 Ph); 7.76–7.81 (2H, m, H-2,6 Ph); 11.92 (1H, br. s, NH). 19F NMR spectrum, δ, ppm: 83.9 (s, CF3). Found, m/z: 362.1115 [М+H]+. С18Н15F3N3O2. Calculated, m/z: 362.1111.

8-Bromo-4-phenyl-4-(trifluoromethyl)-2,4-dihydrochromeno[ 3,4- d ][1,2,3]triazole (10e). Yield 74% (DMSO), 71% (DMF), mp 185–186°C. IR spectrum, ν, cm−1: 3289, 1621, 1471, 1450, 1426, 1311. 1H NMR spectrum, δ, ppm (J, Hz): 7.16 (1H, d, J = 8.8, H-6); 7.34−7.41 (3H, m, H-3,4,5 Ph); 7.44 (1H, dd, J = 8.8, J = 2.4, H-7); 7.71 (2H, dd, J = 6.3, J = 2.5, H-2,6 Ph); 7.89 (1H, d, J = 2.4, H-9); 12.06 (1H, br. s, NH). 13C NMR spectrum, δ, ppm (J, Hz): 81.4 (q, J = 32.2, C-4); 115.8; 116.5; 119.6; 122.9 (q, J = 285.4, CF3); 126.1; 127.1; 128.5; 129.7; 133.6; 133.7; 138.5; 138.6 (br. s); 150.5. 19F NMR spectrum, δ, ppm: 83.7 (s, CF3). Found, m/z: 395.9953 [М+Н]+. С16Н10BrF3N3O. Calculated, m/z: 395.9954.

6,8-Dibromo-4-phenyl-4-(trifluoromethyl)-2,4-dihydrochromeno[3,4- d ][1,2,3]triazole (10f). Yield 77% (DMSO), 74% (DMF), mp 191–192°C. IR spectrum, ν, cm−1: 3290, 1449, 1429. 1H NMR spectrum, δ, ppm (J, Hz): 7.36−7.45 (3H, m, H-3,4,5 Ph); 7.70 (1H, d, J = 2.2, H-7(9)); 7.78−7.88 (3H, m, H-9(7), H-2,6 Ph); 11.98 (1H, br. s, NH). 13C NMR spectrum, δ, ppm (J, Hz): 82.5 (q, J = 32.7, C-4); 112.8; 115.8; 117.5; 122.7 (q, J = 285.4, CF3); 125.2; 127.2; 128.5; 130.0; 133.0; 136.3; 138.3; 138.5; 147.5. 19F NMR spectrum, δ, ppm: 83.5 (s, CF3). Found, m/z: 475.9037 [М+Н]+. С16Н9Br2F3N3O. Calculated, m/z: 475.9039.

X-ray structural study of compounds 7d and 10d was performed at 22°C temperature on an Xcalibur S diffractometer with CCD detector, using the standard procedure (CuKα radiation, graphite monochromator, ω-scanning, 2θmax 56.6°). Crystals suitable for X-ray structural analysis were obtained by slow evaporation of acetonitrile solutions of compounds 7d and 10d. The structures of compounds 7d and 10d were solved by direct method using the SHELX97 software suite.11 The positions of all non-hydrogen atoms were refined independently in anisotropic approximation, the hydrogen atom positions were calculated geometrically and refined according to the “rider” model with dependent temperature parameters. The complete X-ray structural analysis data set for compounds 7d and 10d was deposited at the Cambridge Crystallographic Data Center (deposits CCDC 1527759 and CCDC 1527760, respectively).