An efficient method for preparation of 3,5-diamino-6-chloropyrazin-2-yl alkyl ketones using a novel acetylene hydration method

Catalytic Hydration of Alkynes and Its Application in Synthesis

“…32 The hydration of activated p-donor-(het)aryl-substituted alkynes is readily mediated by p-toluenesulfonic acid (p-TsOH) in alcohols at reflux 33 or with microwave heating. 34 Activated hetaryl-alkynes are also hydrated by stoichiometric sodium sulfidehydrochloric acid aq in methanol 35 (see section 5.1.12 for applications in hetaryl systems). Truly catalytic amounts of trifluoromethanesulfonic acid (TfOH) or trifluoromethanesulfonimide (Tf 2 NH) hydrate alkynes in hot dioxane, 36 and acidic ion-exchange resins mediate the reaction in water at reflux (p-MeOC 6 H 4 C≡CH) 37a or 60-70°C (PhC≡CR).…”

“…Hydration with acid catalysts proceeds with relative ease, 41 especially if the arene bears p-donor substituents; hydration is then mediated by p-toluenesulfonic acid in hot ethanol (Scheme 55a), 33 formic acid (Scheme 3), 42 aqueous trifluoroacetic acid 40 or the reagent sodium sulfide-hydrochloric acid-methanol. 35 Scheme 55 Hydration of internal aryl alkynes. (a) Ref.…”

“…A range of donor-substituted hetaryl alkynes undergo regioselective hydration to hetaroylketones under mild con-ditions, for example in aqueous trifluoroacetic acid (TFA; Scheme 56) 40 or in p-toluenesulfonic acid-methanol, 268 by the reagent sodium sulfide-hydrochloric acid-methanol, 35 and also under mercury(II) catalysis. 269 Scheme 56 Hydration of an indolyl-alkyne in trifluoroacetic acid.…”

Cross‐Coupling of Alkynylsilanols with Aryl Halides Promoted by Potassium Trimethylsilanolate.

“…Data for 1-(1-Heptynyl)-2-methylbenzene (3j): bp: 115 0 C (0.5 mm Hg ABT) 1 H NMR: (500 MHz, CHCl 3 ) 7.36 (d, J = 7.5, 1 H, HC(6')), 7.17-7.18 (m, 2 H, HC(3'), HC(5')), 7.10-7.13 (m, 1 H, HC(4')), 2.46 (t, J =7.0, 2 H, H 2 C(3)), 2.43 (s, 3 H, -CH 3 ), 1.62 (pent, J = 7.5, 2 H, H 2 C(4)), 1.44 (pent, J = 6.5, 2 H, H 2 C(5)), 1.38 (pent, J = 6.5, 2 H, H 2 C( 6)), 0.92 (t, J = 7.5, 3 H, H 3 C(7)) 13 C NMR: (126 MHz, CHCl 3 )…”

Ruthenium-Catalyzed Anti-Markovnikov Hydration of Terminal Alkynes

“…in MeOH. 63 Catalytic amounts of trifluoromethanesulfonic acid (TfOH) or Tf 2 NH hydrate alkynes in hot dioxane, 64 and acidic ion-exchange resins mediate the reaction in water at reflux. 65 Many other procedures use stoichiometric or excess amounts of acid: π-acceptor-alkynes are hydrated by dissolution in cold, concentrated sulfuric acid, followed by dilution with water.…”