Reactions of nitroxides 16. First nitroxides containing tellurium atom

Abstract

2-Chloroethylamine hydrochloride and 3-chloropropylamine hydrochloride were converted with diphenyl ditelluride and sodium borohydride to primary amines containing the tellurium atom. Reaction of tellurium amines with thiophosgene gave the corresponding isothiocyanates, which in turn were transformed with nitroxyl amines to thioureas bearing both a nitroxyl moiety and a tellurium atom. Fungicidal activity of tellurium nitroxides was tested. 1-(2,2,6,6-Tetramethyl-1-oxyl-4-piperidinyl)-3-(3-(phenyltellanyl)propyl) thiourea showed high fungistatic activity against Fusarium culmorum and Phytophtora cactorum.

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Introduction

Both biological properties and synthetic applications of organotellurium compounds are much less known than those of corresponding selenium compounds. Short reviews of synthetic applications¹ and biological activities² of tellurium compounds have been presented. Toxicology and pharmacology of organoselenium and organotellurium compounds were reviewed.³ Organotellurium molecules were featured as biologically active agents.² Antioxidant activities of several selenium and tellurium chrysin derivatives,⁴ tellurium containing phosphonate,⁵ tellurium containing sodium aryloalkylosulfonate,⁶ and tellurium-containing phycocyanins isolated from the tellurium-enriched microalga Spirulina platensis⁷ were reported. Passerini and Ugi products of the chalcogene containing isocyanides, including tellurium, showed antifungal and antibacterial activity.⁸ Four-membered tellurium containing heterocyclic compounds exhibited in vitro and in vivo activity towards Leishmania chagasi.⁹

Numerous quinone aryl tellurides showed activity against cancer cells and considerable potential against inflammatory pathologies.¹⁰ Protease inhibitory activity of tellurium complex of (R,R)-tartaric acid was presented.¹¹ Thiol peroxidase activity of diphenylditelluride was reported.¹² An ethylene glycol derivative containing tellurium showed antibacterial (against Enterobacter cloacae)¹³ and antiinflammatory¹⁴ properties. This compound also prevented type 2 diabetes.¹⁵ A novel dicyclodextrinyl ditelluride compound¹⁶ and hyperbranched polytellurides¹⁷ were recognized as a functional mimic of glutathione peroxidase.

A tellurium-containing cyanine exhibited anticancer activity.¹⁸ Recently, the synthesis of isocyanides with a chalcogene atom (PhX(CH₂)_nNC, X = S, Se, Te) was described. The isocyanides were used in multicomponent Ugi and Passerini reactions to get chalcogene pseudopeptides.⁸ The synthesis of the corresponding starting amines containing the chalcogen unit (PhX(CH₂)_nNH₂, X = Se, Te), necessary to get the isocyanides, was described earlier.^19,20 The amines have also been recently used as building blocks for other compounds.²¹ In the reaction of an excess of bis(trifluoromethyl)nitroxide (CF₃)₂NO with elemental tellurium a new product was obtained.²² On the basis of the balance of the starting (CF₃)₂NO radical and the tellurium content, the product was assigned a formula of [(CF₃)₂NO]₄Te.²² However, to the best of our knowledge, neither stable piperidine nitroxides (TEMPO derivatives) nor pyrrolidine ones (PROXYL derivatives) containing a tellurium atom have been presented in any known literature.

Herein, we would like to describe the synthesis, characterization and evaluation of fungistatic activity of tellurium containing six- and five-membered cyclic nitroxides based on tellurium containing amines PhTe(CH₂)_nNH₂ (n = 2, 3).

Results and discussion

The synthesis of tellurium containing isothiocyanates 4a, 4b and nitroxides 6a–f is presented in Scheme 1.

Scheme 1 Tellurium containing nitroxides 6a–6f.

The starting amines 3a and 3b were synthesized from diphenyl ditelluride 1 and either 2-chloroethylamine hydrochloride (2a) or 3-chloropropylamine hydrochloride (2b), in the presence of sodium borohydride according to Amosowa.²⁰ The amines 3a and 3b were successfully isolated and purified by column chromatography. The reaction of amines 3a and 3b with thiophosgene gave isothiocyanates 4a and 4b. The target tellurium nitroxides 6a and 6b were prepared by the addition of 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (5a), 3-amino-2,2,5,5-tetramethylpyrrolidine-1-oxyl (5b), and 3-aminomethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (5c) to the isothiocyanates 4a and 4b. Amines 3a and 3b and isothiocyanates 4a and 4b were obtained as yellow oils. Nitroxide tellurides were obtained as either red (6a, 6d) or yellow (6b, 6c, 6e, 6f) oils.

The structures of amines 3a and 3b were confirmed by MS (molecular peaks) and were consistent with the literature data.²⁰ The structures of isothiocyanates 4a and 4b were confirmed by the presence of molecular peaks in MS, measurement of exact mass of the molecular peaks in HR MS, full compliance of ¹H and ¹³C NMR spectra (CH₂ signals: DEPT 135°) with the intended structures, measurement of tellurium shift in ¹²⁵Te NMR, and IR spectroscopy, where strong NCS bands at ∼2100 cm⁻¹ were visible. The structures of target tellurium nitroxides 6a–6f were confirmed by EI MS, ESI MS, HR ESI MS, IR and EPR spectra. The NMR spectra were not recorded, due to paramagnetic broadening caused by the presence of an unpaired electron. The molecular peaks in EI MS are present in only negligible abundance (6a, 6c, 6d), although the characteristic tellurium isotopic pattern is recognized. The molecular peaks in EI MS for 6b, 6e, and 6f are almost invisible. A moderately intense peak at m/z 207 was recognized in all EI MS spectra, and was attributed to PhTe according to the characteristic tellurium pattern. A peak at m/z 77 was attributed to Ph. It was the base peak in isothiocyanates 4a and 4b, and also in the target tellurium nitroxides 6b, 6e, and 6f, and was very abundant in 6a and 6c. To confirm the molecular mass, ESI MS was recorded. The ESI MS showed the distinct M + 23 ions in the case of 6b–6f, and a weak M + 2 ion for 6a. HR ESI MS of the ions confirmed their exact mass. In all ESI MS spectra, RNHCSNH(CH₂)_k constitute the parent ions (100%), where R = TEMPO, PROXYL, PROXYL–CH₂. A thioamide band at 1500–1544 cm⁻¹ was observed in the IR spectra. The presence of a nitroxyl moiety was confirmed by recording EPR spectra at low concentration of CHCl₃ (10⁻⁴ mol L⁻¹). The isotropic triplets were recorded. ¹⁴N hyperfine coupling constants (a_N) for the six membered nitroxyl rings (6a, 6d, a_N = ∼1.59 mT) are a little larger than for the five membered nitroxyl rings (6b, 6c, 6e, 6f, a_N = ∼1.45 mT)^23–27 (compared to previously reported compounds^28,29).

Fungistatic activity of tellurium containing nitroxides 6a–6f was evaluated. The results are presented in Table 1.

Table 1 Fungistatic activity of tellurium nitroxides 6a–6f, defined as percent of inhibition of fungal colonies at concentration 200 mg L⁻¹

Cmpd	Alternaria alternata	Botrytis cinerea	Fusarium culmorum	Phytophtora cactorum	Rhizoctonia solani
6a	62	60	77	74	50
6b	48	60	72	45	50
6c	56	66	70	60	55
6d	—	70	81	100	55
6e	64	66	74	69	55
6f	—	64	67	71	48

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Tellurium nitroxides 6a–6c, 6e and 6f showed a medium fungistatic activity. 6d showed a good fungistatic activity against F. culmorum and a strong fungistatic activity against P. cactorum.

Lanosterol 14-alpha-demethylase is a key enzyme in the biosynthetic pathway of ergosterol, the predominant sterol in the cell membranes of most fungi.³⁰ Because organotellurium compounds can react with thiol functional groups,^11,31 deactivation of the thiol group of Cys-470 (ref. 32) of lanosterol 14-alpha-demethylase by a organotellurium compound may be responsible for the disruption of the role that the enzyme and its Cys-470 fulfill in the biosynthesis of ergosterol. This concept has been clearly postulated and depicted elsewhere.^33,34 It is interesting to notice that blocking the thiol functional group was also postulated as being responsible for the fungicidal action of chlorothalonil.^35,36

In conclusion, the strategy described here, involving the preparation of thioureas by reaction of isothiocyanates containing tellurium with a nitroxyl amine, was an effective and efficient method for the synthesis of five- and six-membered nitroxides containing tellurium. The fungicidal activity of compound 6d was also shown.

Experimental

General

Nitroxyl amines: TEMPO–NH₂ (5a), PROXYL–NH₂ (5b), PROXYL–CH₂NH₂ (5c), and their precursors were obtained according to known procedures: 4-(acetylamino)-2,2,6,6-tetramethylpiperidine and 4-acetylamino-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO–NHCOCH₃),^37–44 4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl (5a, TEMPO–NH₂),^{38–40,43,44} 3-carbamoyl-2,2,5,5-tetramethylpyrrolidin-1-oxyl (PROXYL–CONH₂),^40,45–47 3-amino-2,2,5,5-tetramethylpyrrolidin-1-oxyl (5b, PROXYL–NH₂),^{40,43,45,48,49} and 3-aminomethylo-2,2,5,5-tetramethylpyrrolidin-1-oxyl (5c PROXYL–CH₂NH₂).^40,45,50,51 Tellurium containing amines 3a, 3b were prepared according to a known procedure²⁰ with some modifications (for the exact protocols, see below). Diphenyl ditelluride (1, CAS 32294-60-3), 2-chloroethylamine hydrochloride (2a·HCl, CAS 870-24-6) and 3-chloropropylamine hydrochloride (2b·HCl, CAS 6276-54-6) were purchased from Aldrich. TLC was carried out on silica gel Merck Alurolle 5562 or Alufolien 5554 with mobile phases: hexane : ethyl acetate (9 : 1); benzene : ethyl acetate (9 : 1); benzene : methanol (9 : 1). TLC visualization was achieved using UV 254 nm light and/or I₂ vapor. Visualization of tellurium containing compounds was achieved by spraying with 1% ethanolic PdCl₂ (dark brown spots on pale beige background). Column chromatography was performed on silica gel 0.040–0.063 mm, 230–400 mesh: Merck 1.09385.1000 or Zeochem 60 hyd. EI MS data (70 eV) were recorded on an AMD 604 and Agilent Technologies 5975 B mass spectrometer. HR EI MS data were recorded using an AMD 604 mass spectrometer. ESI MS and HR ESI MS were recorded using a Micromass LCT apparatus, with methanol as solvent. IR spectra were recorded on an FT/IR Jasco 420 spectrophotometer. The ¹H and ¹³C NMR data were collected using Varian UNITY plus 200 or 500 spectrophotometers at 200 or 500 MHz, respectively. ¹²⁵Te NMR data were recorded using a Bruker DRX 500 Advance (95 MHz). EPR data were recorded using a Bruker ESP 300 E apparatus. The methodology for the fungicidal activity against phytopathogenic fungi was described earlier.⁵²

3-(Phenyltellanyl)ethylamine 3a, 3-(phenyltellanyl)propylamine 3b (according to a known procedure²⁰ with some modifications). The stock sodium borohydride ethanolic solution was prepared by dissolving sodium borohydride (0.378 g, 0.01 mol) in anhydrous ethanol (6.8 mL). A slightly turbid solution was obtained. The solution of Cl(CH₂)_nNH₂ (2a, 2b) was prepared directly in a dropping funnel, by dissolving Cl(CH₂)_nNH₂·HCl (n = 2 for 2a·HCl, n = 3 for 3a·HCl; 0.003 mol) in anhydrous ethanol (5 mL), followed by alkalization with sodium (0.0675 g, 0.003 mol). After ∼15 min a turbid solution of the free amine 2a or 2b was obtained.

The sodium borohydride ethanolic solution was added dropwise under a strict argon atmosphere to the orange solution of Ph₂Te₂ (1, 0.6138 g, 0.0015 mol). Addition was stopped when a permanently colorless solution was obtained (more than 2.5 mL of the sodium borohydride ethanolic solution was necessary). To the colorless solution of the PhTe⁻ anion, a solution of free amine 2a or 2b was added dropwise. The reaction mixture was refluxed for 3 h and cooled to room temperature. The white precipitate was filtered off. The orange filtrate was acidified to pH 4.5–5 with conc. hydrochloric acid (∼470 μL) and evaporated to dryness under reduced pressure. The hydrochloride (3a·HCl: 1.16 g, 3b·HCl: 0.97–1.16 g) was alkalized with 50% potassium hydroxide (10.5 g). The aqueous phase was extracted three times (20 + 5 + 5 mL) with diethyl ether. Ether solution was dried over anhydrous magnesium sulphate, filtered and evaporated to dryness. The orange residues (3a: 1.05 g, 3b: 0.44–0.57 g) were subjected to column chromatography (methanol) to give 3a (0.479 g, 64.3%) and 3b (0.423 g, 53.8%) as yellowish oils.

3-(Phenyltellanyl)ethylamine 3a (M = 248.6). Pale-straw oil, 0.479 g, 64.3%; MS (m/z, int [%]): 251 (24, M), 249 (22), 247 (14), 222 (10), 220 (9), 218 (6), 207 (26, PhTe), 205 (24), 203 (15), 130 (4), 128 (4), 93 (38), 91 (22), 78 (24), 77 (65, Ph), 65 (6), 51 (35), 44 (100); IR (ν, cm⁻¹, neat): 3360, 3280, 3060, 2926, 2850, 1573, 1474, 1432, 1018, 840, 732, 692, 455.

3-(Phenyltellanyl)propylamine 3b (M = 262.6). Pale-straw oil, 0.423 g, 53.8%; MS (m/z, int [%]): 265 (32, M), 263 (30), 261 (19), 228 (2), 226 (2), 207 (24, PhTe), 205 (22), 203 (14), 98 (8), 93 (11), 91 (8), 78 (22), 77 (72, Ph), 58 (100), 57 (18), 56 (20), 51 (33), 50 (12), 41 (13). IR (ν, cm⁻¹, neat): 3360, 3290, 3160, 3150, 2925, 2830, 1573, 1473, 1432, 1018, 731, 692.

3-(Phenyltellanyl)ethyl isothiocyanate 4a, and 3-(phenyltellanyl)propyl isothiocyanate 4b. General procedure. Thiophosgene (0.18 g, 0.00156 mol, 120 μL) in 1 mL of benzene was added dropwise with a syringe to the solution of 3a or 3b (0.0015 mol) and triethylamine (0.34 g, 0.00336 mol, 472 μL) in benzene (4 mL, dried azeotropically) at 0–5 °C with vigorous stirring for 10 min. The reaction mixture was allowed to warm up to room temperature, and then was stirred at room temperature for up to 1 h. The thick, dark reaction mixture was filtered and the precipitate of triethylamine hydrochloride was thoroughly washed with benzene. The benzene filtrate was washed with saturated sodium bicarbonate solution, the aqueous phase was extracted with 2 × 3 mL of benzene, and the organic layers were dried with anhydrous magnesium sulphate. The suspension was filtered and the solvent was evaporated. The concentrated residues (4a: 0.46 g; 4b: 0.4–0.5 g) were subjected to column chromatography (hexane : ethyl acetate 9 : 1) to give 4a and 4b (4a: 0.299 g, 68.7%; 4b: 0.36 g, 78.8%) as pale-straw oils. Alternatively, the benzene filtrate can be evaporated without washing with the sodium bicarbonate solution and the concentrated benzene filtrate can be directly purified by column chromatography.

2-(Phenyltellanyl)ethyl isothiocyanate, 4a (M = 290.6).

A pale-straw oil, 0.299 g, 68.7%; MS (EI, m/z, int [%]): 293 (60, M), 291 (55), 289 (34), 288 (14), 287 (9), 265 (10), 263 (9), 261 (6), 235 (8), 233 (7), 231 (5), 207 (67, PhTe), 205 (63), 203 (39), 202 (16), 201 (10), 130 (6), 128 (6), 126 (3), 91 (29), 86 (19), 77 (100, Ph), 60 (8), 51 (40); HR MS (EI, 70 eV, m/z): calcd for C₉H₉NS¹³⁰Te: 292.9518, found: 292.9532; ¹H NMR (500 MHz, δ, CDCl₃): 3.08 (t, 2H, J = 7.7 Hz, PhTeCH₂CH₂NCS), 3.81 (t, 2H, J = 7.6 Hz, PhTeCH₂CH₂NCS), 7.23–7.27 (m, 2H, Ph), 7.33–7.37 (m, 1H, Ph), 7.77–7.80 (m, 2H, Ph). ¹³C NMR (125 MHz, δ, CDCl₃): 6.47 (CH₂), 47.15 (CH₂NCS), 110.03 (Car), 128.55 (CHar), 129.55 (CHar), 139.38 (CHar). ¹²⁵Te NMR (157.7 MHz): 492.7 ppm; IR (ν, cm⁻¹, neat) 2061, 1572, 1472, 1433, 1337, 1017, 731, 690.

3-(Phenyltellanyl)propyl isothiocyanate, 4b (M = 304.6).

A pale-straw oil, 0.36 g, 78.8%; MS (EI, m/z, int [%]): 307 (86, M), 305 (78), 303 (47), 274 (8), 272 (7), 270 (5), 235 (3), 233 (3), 207 (56, PhTe), 205 (53), 203 (33), 176 (66), 149 (16), 130 (7), 128 (7), 117 (6), 100 (17), 91 (17), 77 (100, Ph), 72 (70), 51 (37), 41 (24); HR MS (EI, 70 eV, m/z): calcd for C₁₀H₁₁NS¹³⁰Te: 306.9675, found: 306.9678; ¹H NMR (500 MHz, δ, CDCl₃): 2.11 (pseudoquintet, 2H, J = 6–7 Hz, PhTeCH₂CH₂CH₂NCS), 2.93 (t, 2H, J = 7.43 Hz, PhTeCH₂CH₂CH₂NCS), 3.59 (t, 2H, J = 7.43 Hz, PhTeCH₂CH₂CH₂NCS), 7.21–7.26 (m, 2H, Ph), 7.29–7.33 (m, 1H, Ph), 7.72–7.75 (m, 2H, Ph); ¹³C NMR (125 MHz, δ, CDCl₃): 3.90 (CH₂), 31.91 (CH₂), 46.65 (CH₂NCS), 110.78 (Car), 128.06 (CHar), 129.43 (CHar), 138.69 (CHar); ¹²⁵Te NMR (157.7 MHz) 479.0 ppm; IR (ν, cm⁻¹, neat): 3100, 2924, 2850, 2190, 2104, 1573, 1473, 1433, 1343, 1163, 1018, 732, 692, 453.

Tellurium nitroxides 6a–6f, general procedure

2-(Phenyltellanyl)ethyl isothiocyanate (4a, 0.111 g, 0.382 mmol) or 2-(phenyltellanyl)propyl isothiocyanate (4b, 0.116 g, 0.382 mmol) and anhydrous benzene (1–2 mL) were placed in the reaction flask. The solution of nitroxyl amine 5a, 5b or 5c (0.421 mmol, 10% excess) in anhydrous benzene (0.5 mL) was added with a syringe at 22 °C. The stirring was continued at ambient temperature until the starting materials (corresponding isothiocyanate and nitroxyl amine) disappeared (TLC, benzene : methanol 9 : 1). Benzene was evaporated under reduced pressure. The residues (0.16–0.22 g) were subjected to column chromatography (mobile phase: benzene : methanol 9 : 1) to give the red (6a, 6d) or yellow (6b, 6c, 6e, 6f) tellurium nitroxides as oils.

1-(2,2,6,6-Tetramethyl-1-oxyl-4-piperidinyl)-3-(2-(phenyltellanyl)ethyl) thiourea, 6a (M = 461.6).

0.153 g, 86.7%, MS (EI, m/z, int [%]): 465 (1), 464 (1, M), 463 (1), 462 (1), 461 (1), 460 (1), 449 (1), 447 (1), 445 (1), 414 (12), 412 (22), 410 (24), 408 (16), 407 (6), 406 (9), 337 (2), 335 (3), 333 (3), 331 (2), 284 (15), 282 (14), 280 (9), 257 (42), 242 (16), 226 (20), 207 (33, PhTe), 205 (31), 203 (19), 170 (87), 155 (44), 154 (39), 140 (68), 129 (19), 128 (20), 127 (34), 124 (100), 109 (21), 103 (81), 98 (19), 77 (94, Ph), 58 (45), 55 (30), 51 (39), 41 (36); MS (ESI, m/z, int [%]): 487 (1, M + 23), 485 (1), 483 (0.5), 466 (4, M + 2), 464 (3), 462 (1), 258 (90), 257 (100, TEMPO–NHCSNH(CH₂)₂); HR MS (ESI, m/z): calcd for C₁₈H₂₈N₃OS¹³⁰TeNa [M + 23]⁺: 487.0913, found, m/z: 487.0910. HR MS (ESI, m/z): calcd for C₁₈H₃₀N₃OS¹³⁰Te [M + 2]⁺: 466.1172, found, m/z: 466.1170; IR (ν, cm⁻¹, neat): 3321, 2973, 2950, 1621, 1540, 1472, 1440, 1360, 1312, 1241, 1170, 1018, 732, 690; EPR: g = 2.01172, a_N = 1.59 mT.

1-(2,2,5,5-Tetramethyl-1-oxyl-3-pyrrolidinyl)-3-(2-(phenyltellanyl)ethyl) thiourea, 6b (M = 447.6).

0.071 g, 41.7%; MS (EI, m/z, int [%]): 414 (13), 412 (24), 410 (26), 408 (18), 407 (7), 406 (10), 335 (3), 333 (3), 331 (2), 284 (15), 282 (15), 280 (9), 244 (8), 243 (13), 242 (7), 228 (10), 207 (37, PhTe), 205 (34), 203 (21), 186 (8), 169 (61), 156 (19), 155 (29), 154 (37), 142 (23), 141 (71), 129 (17), 126 (29), 110 (31), 109 (21), 103 (45), 99 (28), 98 (31), 95 (23), 84 (31), 77 (100, Ph), 70 (15), 69 (21), 68 (9), 67 (14), 58 (18), 56 (56), 55 (25), 51 (42), 44 (19), 43 (15), 42 (23), 41 (33); MS (ESI, m/z, int [%]): 473 (12, M + 23), 471 (11), 469 (5), 243 (100, PROXYL–NHCSNH(CH₂)₂); HR MS (ESI, m/z): calcd for C₁₇H₂₆N₃OS¹³⁰TeNa [M + 23]⁺: 473.0757, found, m/z: 473.0746; IR (ν, cm⁻¹, neat): 3329, 2973, 2920, 1542, 1462, 1360, 1340, 1297, 1240, 733, 681; EPR: g = 2.01118, a_N = 1.44 mT.

1-[(2,2,5,5-Tetramethyl-1-oxyl-3-pyrrolidinyl)methyl]-3-(2-(phenyltellanyl)ethyl) thiourea, 6c (M = 461.6).

0.135 g, 76.4%; MS (EI, m/z, int [%]): 465 (3), 464 (3, M), 463 (3), 462 (3), 461 (2), 460 (2), 449 (2), 448 (1), 447 (1), 446 (1), 445 (1), 444 (1), 435 (1), 434 (2), 433 (1), 432 (2), 431 (1), 430 (2), 429 (1), 428 (1), 414 (12), 412 (21), 410 (22), 408 (15), 407 (6), 406 (8), 337 (2), 335 (3), 333 (3), 331 (2), 284 (12), 282 (11), 280 (7), 258 (15), 257 (23), 256 (12), 242 (37), 227 (18), 226 (32), 207 (41, PhTe), 205 (38), 203 (24), 202 (10), 199 (18), 183 (22), 171 (15), 170 (22), 155 (24), 154 (29), 143 (20), 140 (45), 124 (100), 115 (99), 103 (56), 77 (94, Ph), 58 (21), 55 (27), 51 (36), 44 (20), 42 (20), 41 (36); MS (ESI, m/z, int [%]): 487 (35, M + 23), 485 (30), 483 (15), 257 (100, PROXYL–CH₂NHCSNH(CH₂)₂); HR MS (ESI, m/z): calcd for C₁₈H₂₈N₃OS¹³⁰TeNa [M + 23]⁺: 487.0913, found, m/z: 487.0912; IR (ν, cm⁻¹, neat): 3319, 2971, 2920, 1546, 1462, 1433, 1364, 734, 692; EPR: g = 2.01091, a_N = 1.47 mT.

1-(2,2,6,6-Tetramethyl-1-oxyl-4-piperidinyl)-3-(3-(phenyltellanyl)propyl) thiourea, 6d (M = 475.6).

0.070 g, 38.6%; MS (EI, m/z, int [%]): 479 (1), 478 (1, M), 477 (1), 476 (1), 463 (2), 461 (1), 459 (1), 446 (0), 430 (1), 429 (1), 428 (1), 427 (1), 425 (1), 414 (9), 412 (16), 410 (17), 408 (11), 406 (6), 352 (3), 350 (3), 348 (2), 333 (2), 307 (3), 305 (3), 303 (2), 284 (10), 282 (9), 280 (6), 272 (6), 271 (14), 270 (9), 256 (27), 240 (9), 207 (26, PhTe), 205 (24), 203 (15), 199 (14), 197 (13), 184 (32), 169 (13), 166 (10), 154 (25), 141 (24), 140 (31), 124 (100), 117 (49), 109 (13), 98 (23), 84 (23), 77 (67, Ph), 58 (63), 56 (16), 55 (19), 42 (17), 41 (33); MS (ESI, m/z, int [%]): 501 (55, M + 23), 499 (50), 497 (30), 480 (25, M + 2), 478 (22), 476 (14), 271 (100, TEMPO–NHCSNH(CH₂)₃); HR MS (ESI, m/z): calcd for C₁₉H₃₀N₃OS¹³⁰TeNa [M + 23]⁺: 501.1070, found, m/z: 501.1066; IR (ν, cm⁻¹, KBr): 3380, 3238, 2928, 1554, 1505, 1468, 1440, 1363, 1231, 735, 692, 631; EPR: g = 2.01128, a_N = 1.59 mT.

1-(2,2,5,5-Tetramethyl-1-oxyl-3-pyrrolidinyl)-3-(3-(phenyltellanyl)propyl) thiourea, 6e (M = 461.6).

0.101 g, 57.6%; MS (EI, m/z, int [%]): 414 (13), 412 (24), 410 (26), 391 (2), 389 (3), 387 (2), 335 (3), 333 (4), 331 (3), 307 (2), 305 (2), 284 (15), 282 (14), 258 (15), 257 (13), 242 (45), 227 (5), 226 (8), 207 (39, PhTe), 205 (36), 203 (23), 202 (10), 185 (27), 184 (14), 183 (44), 171 (16), 169 (38), 156 (10), 155 (41), 154 (34), 143 (25), 142 (29), 141 (11), 126 (34), 124 (25), 117 (42), 111 (10), 110 (34), 109 (15), 99 (71), 98 (45), 84 (87), 77 (100, Ph), 72 (12), 71 (22), 70 (24), 58 (45), 56 (57), 55 (22), 51 (38), 50 (12), 42 (26), 41 (49); MS (ESI, m/z, int [%]): 951 (2, 2 × M + 23), 949 (4), 947 (5), 945 (2), 487 (90, M + 23), 485 (80), 483 (45), 257 (100, PROXYL–NHCSNH(CH₂)₃); HR MS (ESI, m/z): calcd for C₁₈H₂₈N₃OS¹³⁰TeNa [M + 23]⁺: 487.0913, found, m/z: 487.0905; IR (ν, cm⁻¹, neat): 3331, 3080, 2972, 1544, 1462, 1440, 1363, 1300, 733, 691; EPR: g = 2.01113, a_N = 1.44 mT.

1-[(2,2,5,5-Tetramethyl-1-oxyl-3-pyrrolidinyl)methyl]-3-(3-(phenyltellanyl)propyl) thiourea, 6f (M = 475.6).

0.142 g, 78.1%; MS (EI, m/z, int [%]): 414 (16), 412 (31), 410 (34), 408 (23), 406 (9), 337 (2), 335 (4), 333 (4), 331 (3), 307 (1), 305 (1), 284 (19), 282 (18), 280 (11), 271 (11), 270 (16), 256 (6), 240 (23), 207 (39, PhTe), 205 (35), 203 (21), 198 (5), 184 (15), 169 (8), 154 (43), 141 (25), 140 (19), 130 (12), 129 (24), 124 (17), 117 (20), 109 (10), 102 (10), 84 (9), 77 (100), 74 (12), 69 (19), 58 (18), 57 (10), 56 (18), 55 (13), 51 (40), 50 (13), 41 (36); MS (ESI, m/z, int [%]): 501 (75, M + 23), 499 (65), 497 (35), 477 (20), 475 (18), 473 (10), 464 (5), 462 (4), 460 (3), 448 (10), 446 (8), 444 (5), 430 (2), 428 (2), 426 (1), 383 (10), 271 (100, PROXYL–CH₂NHCSNH(CH₂)₃); HR MS (ESI, m/z): calcd for C₁₉H₃₀N₃OS¹³⁰TeNa [M + 23]⁺: 501.1070, found, m/z: 501.1062; IR (ν, cm⁻¹, neat): 3325, 3080, 2971, 1550, 1462, 1364, 734, 682; EPR: g = 2.01113, a_N = 1.45 mT.

Acknowledgements

We would like to thank Mrs Bogusława Wantusiak for assistance in the syntheses of all described compounds. We are grateful to Dr Jadwiga Szydłowska (University of Warsaw, Chemical Department) for performing the EPR measurements.

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Footnote

† Part 15: J. Zakrzewski and B. Huras, Reactions of nitroxides 15. Cinnamates bearing a nitroxyl moiety synthesized using a Mizoroki-Heck cross-coupling reaction, Beilstein J. Org. Chem., 2015, 11, 1155–1162.

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