Photo-oxidative Ruthenium(II)-Catalyzed Formal [3 + 2] Heterocyclization of Thioamides to Thiadiazoles

Abstract

An operationally simple and sustainable one-pot photo-oxidative formal [3 + 2] heterocyclization of β-ketothioamides with aryldiazonium salts catalyzed by Ru­(bpy)3Cl2 has been realized to provide 2,4-disubstituted 5-imino-1,2,3-thiadiazoles in good to high yields under mild reaction conditions for the first time. The reaction proceeded via an α-phenylhydrazone adduct of thioamides leading to 1,2,3-thiadiazoles via N–S bond formation at room temperature. Notably, the products possess Z-stereochemistry with regard to the exocyclic CN double bond at the 5-position of the ring.

Electrochemical Synthesis of 1,2,3-Thiadiazoles from α-Phenylhydrazones

“…Our group has concentrated on transformation of ketothioamides (KTAs) to various heterocyclic scaffolds . Recently, a Ru­(II)-catalyzed photo-oxidative protocol for the synthesis 1,2,3-thiadiazoles from the α-phenylhydrazone adduct of KTAs was reported by our group . During the mechanistic investigation of the Ru­(II)-catalyzed photo-oxidative protocol, we found that the oxidative potentials of α-phenylhydrazone adducts are much lower ( E ox = 0.72 and 0.95 V); hence, it could be easy to oxidize them at the anode without any external support.…”

“…19 Recently, a Ru(II)-catalyzed photo-oxidative protocol for the synthesis 1,2,3-thiadiazoles from the α-phenylhydrazone adduct of KTAs was reported by our group. 20 During the mechanistic investigation of the Ru(II)-catalyzed photo-oxidative protocol, we found that the oxidative potentials of α-phenylhydrazone adducts are much lower (E ox = 0.72 and 0.95 V); hence, it could be easy to oxidize them at the anode without any external support. Keeping in mind the importance and reactivity of hydrazones and as part of our ongoing research to develop an efficient synthetic protocol for thiadiazoles, herein, we report a reagent-less electro-oxidative protocol for the synthesis of 28 fully substituted 1,2,3-thiadiazoles from αphenylhydrazone adducts of KTAs at room temperature (Scheme 1b).…”

“…26 The product was obtained as a pale yellow solid (86%, 154 mg, purified by silica gel column chromatography eluting with 2% ethyl acetate in 98% hexane): mp 134−136 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 16.52 (s, 1H), 13.51 (s, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 6.7 Hz, 2H), 7.58−7.55 (m, 1H), 7.48−7.45 (m, 4H), 7.34−7.28 (m, 3H), 7.14 (d, J = 8.0 Hz, 3H); 13 C{ 1 H} NMR (125 MHz, CDCl 3 ) δ 196.0, 184.7, 141.5, 139.7, 137.6, 131.4, 130.4, 129.6, 129.0, 127.6, 127.3, 125.9, 125.7, 125.0, 116.6. 20,26 The product was obtained as a yellow solid (90%, 167 mg, purified by silica gel column chromatography eluting with 2% ethyl acetate in 98% hexane): mp 132−134 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 16.40 (s, 1H), 13.53 (s, 1H), 7.71 (d, J = 7.6 Hz, 2H), 7.67 (d, J = 7.6 Hz, 2H), 7.45 (t, J = 8.1 Hz, 2H), 7.31 (t, J = 7.6 Hz, 3H), 7.26 (d, J = 7.6 Hz, 2H), 7.17 (d, J = 7.6 Hz, 2H), 7.13 (t, J = 7.6 Hz, 1H), 2.46 (s, 3H); 13 C{ 1 H} NMR (125 MHz, CDCl 3 ) δ 195. 4, 184.6, 142.3, 141.6, 137.6, 136.7, 130.9, 129.6, 129.0, 128.4, 127.2, 126.1, 125.5, 125.0, 116.6, 21.7.…”

“…The product was obtained as a yellow solid (75%, 127 mg purified by silica gel column chromatography eluting with 2% ethyl acetate in 98% hexane): mp 110−112 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 16.74 (s, 1H), 13.67 (s, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.44−7.40 (m, 6H), 7.29 (d, J = 8.0 Hz, 1H), 7.21−7.20 1H), 2.93 (d, J = 7.0 Hz, 2H), 2.28−2.24 (m, 1H), 1.03 (d, J = 7.0 Hz, 6H); 13 C{ 1 H} NMR (125 MHz, CDCl 3 ) δ 203. 3, 184.6, 141.7, 137.7, 129.7, 128.9, 127.1, 125.8, 124.9, 116.6, 47.5, 26.5, 23.0 20 The product was obtained as an orange solid (75%, 134 mg, purified by silica gel column chromatography eluting with 10% ethyl acetate in 90% hexane): mp 111−113 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 8.11−8.09 (m, 2H), 7.60 (t, J = 7.6 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.43 (t, J = 7.6 Hz, 2H), 7.38−7.24 (m, 4H), 7.23−7.17 (m, 2H), 7.14 (d, J = 7.6 Hz, 2H); 13 C{ 1 H} NMR (125 MHz, CDCl 3 ) δ 185. 6, 158.9, 154.4, 142.0, 141.4, 138.1, 132.9, 130.2, 130.0, 129.8, 128.2, 126.2, 125.7, 119.3, 117.8.…”

“…3, 159.1, 154.3, 143.9, 142.3, 141.5, 135.4, 130.4, 130.0, 129.7, 129.0, 126.0, 125.7, 119.4, 117.8, 21.8. 20 The product was obtained as an orange solid (72%, 133 mg, purified by silica gel column chromatography eluting with 10% ethyl acetate in 90% hexane): mp 129−131 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 7.59 (d,J = 6.7 Hz,1H),3H),6H),2H), 7.16 (d, J = 8.0 Hz, 2H), 2.53 (s, 3H); 13 C{ 1 H} NMR (125 MHz, CDCl 3 ) δ 188. 6, 158.5, 154.7, 142.6, 141.3, 139.2, 137.6, 131.1, 130.7, 130.0, 129.6, 126.4, 125.7, 125.1, 119.3, 117.9, 20.6.…”