Pyridone–pyridol tautomerism in 2-hydroxypyridines with [5,6]-annelated rings and oxygen at the [6]-position: 2,3-dihydro-6-hydroxy-4-methylfuro[2,3-b]pyridine and 3,4-dihydro-7-hydroxy-5-methylpyrano-[2,3-b]pyridine

Abstract

V. spectra in a range of solvents, i.r. and l H n.m.r. spectra, and ionization constants in water have been determined for the title compounds (I) to (IV) and their 0and N-methylated derivatives (V) to (VIII). Replacement of the annelated five-membered ring by a six-membered one (a) reduces the ratio [pyridol]/[pyridone] (KT) by a factor of ca. 15-30; ( b ) raises the base strength of the 2-methoxypyridine; (c) scarcely changes the base strength of the 2-pyridone; (d) lowers the acid strength of the 2-pyridone. The greater part of the ring-size effect on the tautomeric equilibrium is attributable to a Mills-Nixon-Brown type of ring strain, which is present in the five-membered ring in (11) but absent from the six-membered one in (IV) ; this strain is relieved by conversion into the pyridol (I), and by ionization; in part the ring-size effect is due to electron-withdrawal by the (strained) five-membered ring. In cation formation by the 2-pyridone (11) this electron-withdrawal and relief of ring strain oppose and almost cancel one another. 2-Hydroxy-6-methoxypyridine is intermediate between [(I), (11)] and [( 111), (IV)] in both tautomeric equilibrium constants and ionization constants, but when allowance is made for the effect that a 4-and 5-alkyl group is expected to have in the first-named compound it is found that the properties of the pyrano-compound are quite similar to those of the ' open-chain ' counterpart, whereas those of the furocompound are normally different. In the solid state all three above compounds exist in the pyridone form. Differences in zwitterionic character between the furopyridones and the pyranopyridones are shown not to be significant.In an Appendix attention is drawn to the relatively large errors in KT values derived by some common pK -KT relations.

Mechanism of bromination of 4(3H)-pyrimidinone and its N-methyl derivatives in aqueous acidic solution. Unusual acidity dependence in the dehydration of observable intermediates

“…Bromo-4(3fl>pyrimidinone (4, R2 = H) as the hydrobromide salt (6, Rj = R2 = H, anion = Br"): yield 57%; mp (EtOH) 239-241 °C dec (lit.25 243-246 °C dec, 252-255 °C dec); NMR (D20/DSS) 8.80 (d, 1), 9.34 (d, 1), J2,6 = 1.0 Hz. 5-Bromo-3-methyl-4-pyrimidinone (4, R2 = Me): vield 62%; mp (EtOH-ligroin) 152-155 °C (lit.26 158-159 °C); NMR (CDCl3/Me4Si) agreed with literature values.26 5-Bromo-l-methyl-4-pyrimidinone (5, R4 = Me) as the hydrobromide salt (6, Ri = Me, R2 = H, anion = Br"): yield 40%; mp (H20) 243-244 °C dec; NMR (D20/DSS) 3.85 (s, 3), 8.38 (d, 1),8.70 (d, 1), J26 = 2.2 Hz; UV in TableIV. Anal.…”

“…We anticipate that the medium dependences of /10 and (8) The chemical shifts reported in Table I are fully consistent with cationic structures for the intermediates. In particular ~9 for the 2-H militates against a neutral structure.…”

Strained heterocyclic systems. VI. Basicities of some quinoxalines

“…1.23 Quinoxaline (7) 548 1.03" 2,3-Diphenyl quinoxaline (8) 564 0.85 Acenaphtho[1,2-6]quinoxaline (9) 573 0.72 Benzo [3,4] cyciobuta [ 1,[2][3][4][5][6] quinoxaline (3) 5818 0.62 Dibenzo[a,c]phenazine (10) 607 0.30 " Duplicate runs, ±2 mV, at 25°unless otherwise stated. 6 At 30°.…”

“…It has recently been established that a fused strained ring adjacent to the nitrogen atom in a quinoline ring causes a marked decrease in the basicity of such heterocyclic compounds.2-4 These observations are in accord with the concept of orbital rehybridization developed by Streitwieser and coworkers to account for the changes in kinetic acidity and reactivity toward electrophilic substitution observed With strained carbocyclic systems.8 This interpretation has gained support from a variety of studies: J (18C-H) nmr data,6•7 esr data,8•9 rates of protodesilylation,10 polarographie reduction potentials,11 and molecular orbital calculations. 12 In our earlier studies of 1,2-dihydrocyclobuta [b ]quinoline (1) and acenaphtho [1,[2][3][4][5][6]quinoline (2) decreases in basicity of ten-and fivefold, respectively, were observed relative to model compounds. Since there is greater strain in biphenylene than in benzocyclobutene,13 it was anticipated that pKa data for an azabiphenylene would exhibit a further substantial decrease in basicity.…”

“…Since there is greater strain in biphenylene than in benzocyclobutene,13 it was anticipated that pKa data for an azabiphenylene would exhibit a further substantial decrease in basicity. Although no monoazabiphenylenes have been reported in the literature, the diazabiphenylene, benzo [3,4 [cyciobuta [1,[2][3][4][5][6] [quinoxaline (3), has 3 been known for some time.14 This report, therefore, presents the synthesis and basicity measurements of a series of strained quinoxaline derivatives.…”