The tautomerism of heteroaromatic compounds with five-membered rings—VII Isoxazolin-3-ones—3-hydroxyisoxazoles

The preparation of some 3-hydroxyisoxazoles from β-keto-esters and the proof of their structure is described. These compounds are shown to exist largely in the hydroxy form.     

Benzoin condensation reactions of 5-membered heterocyclic compounds

Benzoin condensation reactions of 2-thiophenecarboxaldehydes and furfurals have been reexamined with catalysts such as potassium cyanide, cyanide-resin, and a thiazolium salt. 2-Thiophenecarboxaldehydes gave both thenoins and thenils while furfurals gave only furoins. Possible routes which might lead to formation of thenils were investigated.     

The tautomerism of 5-aminotetrazole

In the reaction of 5-amino-1-methyltetrazole and 5-amino-2-methyltetrazole with carboxylic acid anhydrides or chlorides, diacylamides are obtained in addition to monoacyl derivatives. The results of independent synthesis and a study of IR and PMR spectra have shown that in the diacylamides considered both acyl groups are attached to the same (the exocyclic) nitrogen atom.For part VI, see [1].     

Geometry and tautomerism of sapphyrin—DFT studies

The structure and total energy have been investigated, applying the density functional theory (DFT), for idealized sapphyrin derivatives, created by replacements of meso-phenyl groups of 5,10,15,20-tetraphenylsapphyrin or β-alkyl groups of decaalkylsapphyrin with hydrogens or two methyl groups, respectively. The following species have been considered: the dication of plain sapphyrin (SapH₅²⁺) 12,13-dimethylsapphyrin (12,13-DMSapH₃), 12,13-dimethylsapphyrin dication (12,13-DMSapH₅²⁺), and the 10,15-dimethylsapphyrin dication (10,15-DMSapH₅²⁺). To address the issue of tautomerization the calculations have been carried out for the six feasible distribution patterns of NH protons among the five nitrogen centers of the planar sapphyrin P0_i (i=1–6). The B3LYP/6-31G optimized bond lengths and angles of sapphyrin or (dimethylated sapphyrin) skeletons are in satisfactory agreement with X-ray crystallographic values determined for decaalkylsapphyrin dications. The calculated total energies, using the B3LYP/6-31G**//3-21G approach demonstrate that the plain sapphyrin and 12,13-dimethylsapphyrin dications favor the planar geometry of the macrocycle. Localization of the methyl groups at the 10,15-meso positions of sapphyrin reversed the order of stability leading to the energy preference for the inverted structure. Thus, this steric factor related to the meso substitution seems to be instrumental in the C pyrrolic ring inversion. The DFT calculation also provided the relative stability frame for the complex tautomeric equilibria of SapH₃ which involve six different forms. Their relative stability decreases in the range: {25-NH, 26-N, 27-NH, 28-NH, 29-N} P0₃>({25-NH, 26-N, 27-NH, 28-N, 29-NH} P0₁>{25-NH, 26-NH, 27-N, 28-NH, 29-N} P0₅>{25-N, 26-NH, 27-NH, 28-NH, 29-N} P0₂>{25-NH, 26-N, 27-N, 28-NH, 29-NH} P0₆>{25-N, 26-N, 27-NH, 28-NH, 29-NH} P0₄. The stability order can be qualitatively related to the number and the nature of the cis NH interactions present in the sapphyrin core.     

The oxidation of compounds capable of imine-enamine tautomerism with lead tetraacetate

Compounds capable of imine-enamine tautomerism react preferentially via their enamine tautomer giving a 2-acetoxyaldehyde which equilibrates with the starting imine. This derives from the extra nucleophilicity of the β-carbon of the enamine tautomer. The reaction of the imine isomer to form an aryl- or an alkylnitrenoid species is a minor pathway.     

The directed ortho metalation — Cross-coupling symbiosis in heteroaromatic synthesis

Thirty years after its discovery by Gilman and Wittig, the Directed ortho Metalation (DoM) reaction continues to march in synthetically useful paths. To offer evidence for this statement, this lecture review describes a new and general cumyl Directed Metalation Group (DMG) (Schemes 2–6) and a phosphine oxide DMG (Schemes 7 and 8). Aryl-aryl cross-coupling chemistry is highlighted by polymer support Suzuki-Miyaura (Schemes 10 and 11) and an aryl O-carbamate-Grignard of value in the construction of naphthalenes (Scheme 12) and indoles (Scheme 13) and, for the latter class of compounds, in the generation of 4,5-quinodimethane intermediates (Scheme 14) for the synthesis of corresponding annelated derivatives (Scheme 15). The marriage of DoM with the Negishi cross-coupling reaction is demonstrated in general (Scheme 16). The concept of Directed remote Metalation (DreM) (Schemes 17 and 19) is applied to the synthesis of dibenzopyranones (Scheme 18), xanthones (Scheme 21), acridones, dibenzoazepinones, and oxindoles (Scheme 20). In this context, a carbanionic N-to-ortho-C t-Boc migration leading to anthranilate esters is also achieved (Scheme 20). For provision of diaryl ethers, diaryl sulfides, and diaryl amines, a new copper catalyst is introduced into the venerable Ullmann reaction (Scheme 22) and its extension by DoM, and cross-coupling chemistry is indicated (Scheme 23). A recently evolving link to DoM, the Grubbs metathesis process is manifested in the total synthesis of two natural products (Schemes 25 and 26) and has anticipated use more broadly in heterocyclic synthesis. (Scheme 27).     

Palladium-catalyzed cross-coupling of 5-acyl and 5-formyl-1,2,4-triazines and their derivatives with heteroaromatic tin compounds

The synthesis of novel mono- and di(substituted)-1,2,4-triazine derivatives containing thiophene and furan rings are described. Heteroaromatic rings were provided using palladium-catalyzed cross-coupling reaction between 3-alkylsulfanyl-5-acyl-1,2,4-triazines or 5-cyano-3-alkylsulfanyl-1,2,4-triazines and heteroaromatic tin compounds. New compounds bearing masked acyl groups were also obtained. These reactions were optimized to determine the scope and limitations of this methodology and were used for preparation of oligothiophenes bearing terminal heterocyclic ring.     

The sulfonation of aromatic and heteroaromatic polycyclic compounds

Relative reactivities of a series of polycyclic carbo- and heteroaromatic compounds to sulfonation by sulfur trioxide in nitrobenzene are measured and discussed. The results show the following reactivity in decreasing order: indole, carbazole, pyrene, perylene, naphthalene, phenanthrene, benzene, benzothiophene, and dibenzothiophene.     

Hydro­gen bonding in proton‐transfer compounds of 5‐sulfosalicylic acid with bicyclic heteroaromatic Lewis bases

The crystal structures of quinolinium 3‐carboxy‐4‐hydroxy­benzene­sulfonate trihydrate, C₉H₈N⁺·C₇H₅O₆S⁻·3H₂O, (I), 8‐hydroxy­quinolinium 3‐carboxy‐4‐hydroxy­benzene­sulfonate monohydrate, C₉H₈NO⁺·C₇H₅O₆S⁻·H₂O, (II), 8‐amino­quinolinium 3‐carboxy‐4‐hydroxy­benzene­sulfonate dihydrate, C₉H₉N₂⁺·C₇H₅O₆S⁻·2H₂O, (III), and 2‐carboxy­quinolinium 3‐carboxy‐4‐hydroxy­benzene­sulfonate quinolinium‐2‐carboxylate, C₁₀H₈NO₂⁺·C₇H₅O₆S⁻·C₁₀H₇NO₂, (IV), four proton‐transfer compounds of 5‐sulfosalicylic acid with bicyclic heteroaromatic Lewis bases, reveal in each the presence of variously hydrogen‐bonded polymers. In only one of these compounds, viz. (II), is the protonated quinolinium group involved in a direct primary N⁺—H⋯O(sulfonate) hydrogen‐bonding interaction, while in the other hydrates, viz. (I) and (III), the water mol­ecules participate in the primary intermediate interaction. The quinaldic acid (quinoline‐2‐carboxylic acid) adduct, (IV), exhibits cation–cation and anion–adduct hydrogen bonding but no direct formal heteromolecular interaction other than a number of weak cation–anion and cation–adduct π–π stacking associations. In all other compounds, secondary interactions give rise to network polymer structures.     

NMR study of 4-membered rings. VIII—The sign of the four-bond couplings in adducts of cyclopentenone with vic-dichloroethylenes

The proton spectra of the four stereoisomers prepared by photocycloaddition of 2-cyclopentenone to cis and trans dichloroethylene have been analysed using tickling and INDOR techniques in order to obtain the sign of the cross-ring four-bond coupling constants in the cyclobutane ring. These parameters are correlated with the relative orientation of the protons involved. The complete NMR analysis of the seven-spin system of the cycloadduct endo-7-phenoxybicyclo[3.2.0]hept-2-en-6-one has been carried out and all the four-bond coupling constants have been obtained and discussed. The sign of the cross-ring coupling in the cyclobutanone ring has been determined.     

Conformational studies by dynamic NMR—VI: Torsional barriers in 5-membered heteroaromatic carbamides and thiocarbamides

Thermodynamie parameters involved in the rotation of the partial C-N double bond in a series of 5-membered heteroaromatic N,N-dimethyl-carbamides and -thiocarbamides have been measured by total line shape (TLS) analysis of their NMR. Lanthanide induced shift (LIS) has been applied in two cases to determine the conformation of the CO moiety with respect to the heteroatom. The energy barriers of thiazolyl carbamides and thiocarbamides were found to be larger than those of furyl and thienyl analogues, and explained in terms of a perturbational molecular orbital analysis.     

Saturated 5-membered ring conformations. 2—1H NMR study of protonated N-methylpyrrolidines

The ¹H NMR spectra of the protonated and unprotonated forms of cis- and trans-N-methylhexahydroisoindoline, of 1,3,3,4,4-pentamethylpyrrolidine and of 1,3,3-trimethylpyrrolidine were analyzed. The coupling constants between the NH⊕ and the CH protons α to the nitrogen allowed the study of the conformation of the cyclic systems in pseudorotation.     

The synthesis of heteroaromatic nitro compounds from 3-nitrochromone

3-Nitrochromone ( 1 ) reacts with a series of nucleophiles by Michael addition followed by intramolecular condensation to yield pyrrolyl ( 2 ), phenyl ( 3 ), pyridyl ( 4 ), pyrido ( 5,6 ), pyrimidyl ( 7 ) and pyrazolyl ( 8 ) nitro derivatives. The reactions proceed under basic catalysis in 39–78% yields. Conversion of 4 to 3,4-dihydrobenzofuro[3,2-b]quinol-1-(2H)one ( 12 ) is also described. Carbon-13 data for 2, 5, 6 and 8 are discussed. The one bond C,H coupling constants in the nitropyridines are also reported and used as an analytical tool.     

Reaction of heteroaromatic compounds with carbenes (review)

The literature data on the reactions of heteroaromatic compounds of various classes with halo-, alkyl-, alkoxy-, and ketocarbenes are examined. The mechanisms of these reactions and the effect of the methods used to generate the carbenes and the nature of the heterocycle on the direction of the reaction and the structures and yields of the final products are discussed. An estimate of the possibilities of the preparative utilization of the indicated reactions is given.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 723–743, June, 1982.     

Uracil–4-Hydroxyuracil tautomerism revisited

The tautomerism of the uracil-4-hydroxyuracil system is examined with the 3–21G basis set and full geometry optimization using gradient techniques. Single-point calculations at the 6-31G level were also done and the results compared with the 2-pyridone–2-hydroxypyridine system. The best ΔE(taut) obtained in this work is 74.1 kJ/mol.