1,2,3-Benzotriazine Sulfonamides. A New Class of Oral Diuretic Agents¹

Abstract

Phenoxymethylpenicillin sulfoxide benzyl ester (IVb).Phenoxymethylpenicillin benzyl ester was much more resistant to oxidation with sodium periodate. A solution of 4.7 g. (0.0107 mole) of phenoxymethylpenicillin benzyl ester lib was stirred with sodium periodate in dioxane-phosphate buffer for 10 hr. at room temperature, then for 4 days with fresh sodium periodate-dioxane-phosphate buffer, and finally for 2 days at 50°with fresh periodate-dioxane-phosphate buffer. The reaction mixture was worked up as with the benzylpenicillin sulfoxide benzyl ester. Evaporation of the chloroform solution gave an oil which crystallized after 9 days to give 2.95 g. (61%) of crude phenoxymethylpenicillin sulfoxide benzyl ester IVb, m.p. 123-125°. Recrystallization from ethyl acetate-petroleum ether gave 2.75 g. (57%) of crystalline solid, m.p. 124-125°.

Potassium Iodide/tert‐Butyl Hydroperoxide‐Mediated Oxidative Annulation for the Selective Synthesis of N‐Substituted 1,2,3‐Benzotriazine‐4(3H)‐ones Using Nitromethane as the Nitrogen Synthon

“…[1] Fore xample,m any pharmacological properties for this class of compounds have been reported, including drugs having sedative, [2] diuretic, [3] anesthetic, [4] antiarthritic, [5] antitumor [6] and antitubercular activities. [1] Fore xample,m any pharmacological properties for this class of compounds have been reported, including drugs having sedative, [2] diuretic, [3] anesthetic, [4] antiarthritic, [5] antitumor [6] and antitubercular activities.…”

“…When the reaction mixture was heated in 2mLo fn itromethane at 120 8 8Cf or 12 h, 3-phenylbenzo[d] [1,2,3]triazin-4(3H)-one (2a)w as obtained in 30% isolated yield, whereas at race amount of 3-phenylquinazolin-4(3H)-one (2a' ')w as detected ( 1, entry 15). as an oxidant.…”

“…As shown in Table 2, various 2-aminobenzamides (1a-1z)w ere employed in this reaction to synthesize av ariety of 1,2,3benzotriazine-4(3H)-ones in good yields.F irst, when R 1 was an aromatic substituent, all of the desired products( 2a-2n)w ere obtained in moderate to good yields.N otably, the reactions of 2-amino-N-arylbenzamides bearing electron-donating groups (4-Me,4 -OMe or 4-t-Bu) on the phenylr ing of R 1 gave higher yields than those of the substrates bearing electronwithdrawing groups (4-CF 3 )ont he phenyl ring. However, 4-phenylbenzo[d] [1,2,3]triazine (8)w as not observed, and a5 0% yield of 4-phenylquinazoline (8a)w as obtainedw hen 2-aminobenzophenone (7)was employed as the substrate.Similarly,w hen nitroethane was used instead of nitromethane,t he reactiono f7 gave2 -methyl-4-phenylquinazoline (8b)w ith a5 9% yield (Scheme 2d). Subsequently,s ubstrates with aliphatic groups, such as benzyl, n-butyl,i sopropyl, cyclohexyl and tertbutyl as R 1 substituents could also be employed to give the corresponding products 2p-2t in 70-86% yields.U nfortunately,2 -aminobenzamide (2u)d id not give the desired product.F inally, 2-aminobenzanilides with various R 2 substituents such as methyl, methoxy, fluoro, chloro and bromo were also employed in this reaction, giving the desired products 2v-2z in 68-85% yields.A mong these reactions,s ubstrates with electron-rich substituents (1v or 1w)g aveh igher yields than those with electron-deficient ones (1x, 1y or 1z) because of the differences in amino nucleophilicity.…”

“…Initially,t he Nef reactiono fC H 3 [15,16] Then, HNO can be further oxidized to HNO 2 by KIO generated in situ from KI and TBHP. Initially,t he Nef reactiono fC H 3 [15,16] Then, HNO can be further oxidized to HNO 2 by KIO generated in situ from KI and TBHP.…”

“…[9] As am inor pathway, 2a' ' can be obtained via at andem condensation-addition-oxidation process of 1a with HCHO. In summary,w eh ave developedat ransition metalfree oxidative annulation for the chemoselective synthesis of N-substituted 1,2,3-benzotriazine-4(3H)-ones and 1-methyl-1H-benzo[d] [1,2,3]triazoleu sing nitromethane as the nitrogen synthon. In summary,w eh ave developedat ransition metalfree oxidative annulation for the chemoselective synthesis of N-substituted 1,2,3-benzotriazine-4(3H)-ones and 1-methyl-1H-benzo[d] [1,2,3]triazoleu sing nitromethane as the nitrogen synthon.…”