Efficient Synthesis of 2-Unsubstituted 1,3-Selenazoles

Abstract

Two new and efficient methods for the synthesis of 2-unsubstituted 1,3-selenazoles, the fragmentation of 2-benzoyl-1,3-selenazoles and the cyclization of α-bromoketones with seleno­formamide, are reported.

Key words

cyclization - fragmentation - selenium heterocycles - oxidation - 1,3-selenazoles

References

• For the antibiotically active C-glycosyl selenazole selenazofurin, see:
• 1a Goldstein BM. Kennedy SD. Hennen WJ. J. Am. Chem. Soc.  1990,  112:  8265 ; and references cited therein
• 1b Shafiee A. Khashayarmanesh Z. Kamal F. J. Sci., Islamic Repub. Iran  1990,  1:  11 
• 1c Shafiee A. Shafaati A. Khamench BH. J. Heterocycl. Chem.  1989,  26:  709 
• 1d For cancerostatic activity of 1,3-selenazoles see: Srivastava PC. Robins RK. J. Med. Chem.  1983,  26:  445 
• 1e Shafiee A. Mazloumi A. Cohen VJ. J. Heterocycl. Chem.  1979,  16:  1563 
• 2a Larsen R. 1,3-Selenazoles, In Comprehensive Heterocyclic Chemistry II, , Shinkai I., Katritzky A., Rees C. W., Scriven E. F. V.   Vol. 3:  Elsevier Science; Oxford: 1996.  Chap. 8.
• 2b Wirth T. Organoselenium Chemistry, in Modern Developments in Organic Synthesis   Springer; Berlin: 2000. 
• 3a Koketsu M. Nada F. Ishihara H. Synthesis  2002,  195 
• 3b Geisler K. Jacobs A. Künzler A. Mattes M. Girrleit I. Zimmermann B. Bulka E. Pfeiffer W.-D. Langer P. Synlett  2002,  1983 
• 3c Kaminski R. Glass RS. Skowronska A. Synthesis  2001,  1308 
• 3d Ishihara H. Koketsu M. Fukuta Y. Nada F. J. Am. Chem. Soc.  2001,  123:  8408 
• 3e Koketsu M. Fukuta Y. Ishihara H. Tetrahedron Lett.  2001,  42:  6333 
• 3f Zhang P.-F. Chen Z.-C. Synthesis  2000,  1219 
• 3g Maeda H. Kambe N. Sonoda N. Fujiwara S.-i. Sini-ike T. Tetrahedron  1997,  53:  13667 
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• 4 Haginiwa J. Yakugaku Zasshi  1948,  68:  191 
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• 6 For 2-benzoyl-1,3-benzoselenazole, see: Mbuyi M. Evers M. Tihange G. Luxen A. Christiaens L. Tetrahedron Lett.  1983,  5873 
• 2-Unsubstituted 1,3-thiazoles have been prepared by decarboxylation of 1,3-thiazolyl-2-carboxylic acids; see for example:
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7

Synthesis of 2-Benzyl-4-phenyl-1,3-selenazole(3a). Typical Procedure. An EtOH solution (20 mL) of α-bromoacetophenone (0.20 g, 1.0 mmol) and phenylseleno-acetic amide (0.20 g, 1.0 mmol) was refluxed for 5 min. After cooling to 20 °C the precipitate was filtered off and recrystallized from EtOH to give 3a as colourless needles (0.29 g, 99%), mp 99.5-100 °C. ¹H NMR (300 MHz, CDCl₃): δ = 4.34 (s, 2 H, CH₂), 7.31-7.90 (m, 10 H, Ar), 7.96 [s, 1 H, ² J (SeH) = 51.3 Hz, 5-H, selenazole]. ¹³C NMR (75 MHz, CDCl₃): δ = 43.28, 118.86 [C-5, ¹ J (C₅Se) = 106.6 Hz], 126.62, 127.33, 127.75, 128.70, 128.87, 129.27, 135.51, 138.34, 155.78, 177.95. ⁷⁷Se NMR (CDCl₃, 60% Me₂Se in CDCl₃): δ = 738.79. IR (KBr): 1042 (s), 1125 (s), 1320 (w), 1420 (m), 1465 (m), 1520 (s), 3050 (w), 3080 (w) cm^-1. MS (70 eV): m/z (%) = 298 (68) [M⁺], 182 (100), 102 (93). Anal. Calcd for C₁₆H₁₃NSe (298.25): C, 64.44; H, 4.39; N, 4.70. Found: C, 6.40; H, 4.20; N, 4.79. All products gave correct spectroscopic data and correct elemental analyses and/or high resolution mass data.

8

Synthesis of 2-Benzoyl-4-phenyl-1,3-selenazole ( 4a). Typical Procedure. To a dioxane solution (20 mL) of 3a (1.49 g, 5.0 mmol) was added SeO₂ (0.55 g, 5.0 mmol) with stirring. The mixture was heated in a water bath at 40 °C for 3 h. The hot solution was subsequently filtered, cooled, and poured into ice water (50 mL). The crystalline precipitate was filtered off, washed (H₂O), dried in vacuo and recrystallized (EtOH) to give 4a as yellow needles (1.09 g, 70%), mp 76-77 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.38-8.62 (m, 10 H, ArH), 8.54 [s, 1 H, ² J (SeH) = 50 Hz, 5-H, selenazole]. ¹³C NMR (75 MHz, CDCl₃): δ = 126.71, 126.77, 128.43, 128.93, 131.45, 133.63, 134.53, 134.92, 158.70, 175.08, 184.67. ⁷⁷Se NMR (CDCl₃, 60% Me₂Se in CDCl₃): δ = 807.31. IR (KBr): 840 (m), 901 (m), 1025 (w), 1050 (w), 1075 (w), 1110 (w), 1190 (m), 1270 (s), 1298 (s), 1430 (s), 1465 (s), 1505 (s) cm^-1. MS (70 eV): m/z (%) = 312 (24) [M⁺], 299 (3), 285 (2), 182 (10), 105 (100), 102 (17), 77 (63), 51 (16), 28 (14). Anal. Calcd for C₁₆H₁₁NOSe (312.22): C, 61.55; H, 3.55; N, 4.49. Found: C, 61.80; H, 3.90; N, 4.29.

9

Synthesis of 4,5-Diphenyl-1,3-selenazole ( 5e). Typical Procedure. An EtOH solution (30 mL) of 2-benzoyl-4,5-diphenyl-1,3-selenazole (4e) (1.65 g, 5 mmol) and NaOH (0.40 g, 10 mmol) was refluxed for 1 h. After cooling, the sodium benzoate formed was filtered off and the solution was poured into ice water. The product was filtered off, dried in vacuo (P₄O₁₀) and recrystallized from petroleum ether to give 5e as beige needles (0.93 g, 77%), mp 73-74 °C. ¹H NMR (200 MHz, CDCl₃): δ = 7.30-7.56 (m, 10 H, ArH), 9.86 [s, 1 H, ² J (SeH) = 57.26 Hz, 2-H, selenazole]. ¹³C NMR (50 MHz, CDCl₃): δ = 127.59, 128.0, 128.34, 128.66, 129.35, 129.84, 133.96. ⁷⁷Se NMR (CDCl₃, 60% Me₂Se in CDCl₃): δ = 806.24, 135.25,149.18, 150.85, 156.78. IR (KBr): 875 (m), 1080 (w), 1190 (w), 1270 (w), 1445 (s), 1495 (m), 1502 (m), 1605 (m), 3080 (m)cm^-1. MS (70 eV): m/z (%) = 285 (60) [M⁺], 257 (13), 204 (15) , 178 (100). Anal. Calcd for C₁₅H₁₁NSe (284.22): C, 63.39; H, 3.90; N, 4.93. Found: C, 63.21; H, 3.94; N, 4.93.

12

Synthesis of Selenoformamide. [11a] To freshly prepared P₂Se₅ (114.18 g, 250 mmol, see ref. [3b] ) was added destilled formamide (37.16 g, 825 mmol). The reaction mixture was stirred at 60 °C for 5 h and was subsequently extracted with dry Et₂O for 8 h using a Soxhlet apparatus. The Et₂O solution of the extract was collected and the precipitated oil was separated, filtered (to remove precipitated selenium) and dried in vacuo. The oil solidified upon standing in the refrigerator. The solid was recrystallized from Et₂O to give 6 as yellow needles, mp 35-37 °C. IR (KBr): 980 (m), 1095 (m), 1170 (m), 1305 (s), 1375 (s), 1415 (s), 1610 (s), 1680 (s), 2330 (w), 2780 (w), 3300 (s, br) cm^-1. Anal. Calcd for CH₃NSe: C, 11.11; H, 2.80; N, 13.02. Found: C, 11.40; H, 3.10; N, 13.11. The solidification of 6 can be achieved only for crude products of good purity. Decomposition of selenoformamide (6) occurred upon standing at 20 °C. However, it can be stored at -20 °C for several days. Freshly prepared material should be used for reactions.

13

Cyclization of 6 with 1d. To an EtOH solution of 6 (1.1 g, 10 mmol) was added 1d (2.4 g, 10 mmol) and pyridine (0.79 g, 10 mmol). The solution was gently warmed, the precipitate formed was filtered off and the filtrate was concentrated. The product precipitated upon standing of the solution at 0 °C and was recrystallized from dry i-PrOH or EtOH to give 5d as slight yellow needles (2.00 g, 79%), mp 160-162 °C.