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.

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 

3h Lai L.-L. Reid DH. Synthesis  1993,  870 

3i Ogawa A. Miyaka J. Karasaki Y. Murai S. Sonoda N. J. Org. Chem.  1985,  50:  384 

3j Cohen VJ. Synthesis  1978,  668 

4 Haginiwa J. Yakugaku Zasshi  1948,  68:  191 

5 Maeda H. Kambe N. Sonoda N. Fujiwara S.-i. Sini-ike T. Tetrahedron  1997,  53:  13667 ; and references cited therein

6 For 2-benzoyl-1,3-benzoselenazole, see: Mbuyi M. Evers M. Tihange G. Luxen A. Christiaens L. Tetrahedron Lett.  1983,  5873 

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.

2-Unsubstituted 1,3-thiazoles have been prepared by decarboxylation of 1,3-thiazolyl-2-carboxylic acids; see for example:

10a Sarodnick G. Kempter G. Pharmazie  1983,  38:  829 

10b Pirotte B. Delarge J. J. Chem. Res., Miniprint  1990,  7:  1634 

10c Strehlke P. Chem. Ber.  1973,  106:  721 

10d Sarodnick G. Kempter G. Z. Chem.  1979,  19:  21 

11a Geisler K. Below H. Möller A. Bulka E. Z. Chem.  1984,  24:  99 

11b For the synthesis of an 1,3-oxaseleno derivative, see: Weber M. Hartmann H. Z. Chem.  1987,  27:  95 

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.