Facile Assembly of Benzo[b]naphtho[2,3‐d]azocin‐6(5 H)‐ones by a Palladium‐Catalyzed Double Carbometalation

The palladium‐catalyzed reaction of 2‐alkynylanilines with 2‐(2‐bromobenzylidene)cyclobutanone as an efficient route to 7,8‐dihydrobenzo[b]naphtho[2,3‐d]azocin‐6(5 H)‐ones was developed. The fused eight‐membered ring was constructed conveniently. During the reaction process, double carbometalation was involved, which resulted in excellent selectivity with the formation of three new bonds. This transformation is highly efficient and leads to fused polycycles in good to excellent yields with good functional group tolerance.     

2,2′‐Anhydro‐1‐(3′,5′‐di‐O‐acetyl‐β‐D‐arabinofuranosyl)uracil,a cyclouridine nucleoside with a C4′‐endo furanosyl conformation

2,2′‐Anhydro‐1‐(3′,5′‐di‐O‐acetyl‐β‐D‐arabinofuranosyl)uracil, C₁₃H₁₄N₂O₇, was obtained by refluxing 2′,3′‐O‐(methoxymethylene)uridine in acetic anhydride. The structure exhibits a nearly perfect C4′‐endo (⁴E) conformation. The best four‐atom plane of the five‐membered furanose ring is O—C—C—C, involving the C atoms of the fused five‐membered oxazolidine ring, and the torsion angle is only −0.4 (2)°. The oxazolidine ring is essentially coplanar with the six‐membered uracil ring [r.m.s. deviation = 0.012 (5) Å and dihedral angle = −3.2 (3)°]. The conformation at the exocyclic C—C bond is gauche–trans which is stabilized by various C—H...π and C—O...π interactions.     

Synthesis of Highly Substituted Cyclobutane Fused‐Ring Systems from N‐Vinyl β‐Lactams through a One‐Pot Domino Process

In this contribution, aminocyclobutanes, as well as eight‐membered enamide rings, have been made from N‐vinyl β‐lactams. The eight‐membered products have been formed by a [3,3]‐sigmatropic rearrangement, whereas the aminocyclobutanes have been derived from a domino [3,3]‐rearrangement/6π‐electrocyclisation process. The aminocyclobutanes have been obtained in a highly diastereoselective fashion. The cyclobutane ring system tolerates fusion even if adjacent quaternary centres are present. Systems containing up to four fused rings are readily accessible. The reaction profile has been investigated by using Gaussian 03. This study suggests that two reaction pathways for aminocyclobutane formation are possible. In one pathway the [3,3]‐sigmatropic rearrangement is the rate‐limiting step and in the second pathway the electrocyclisation is rate limiting. Taken together, these reactions should facilitate the construction of fused heterocycles.     

Studies on the chemical transformations of rotenoids. 6 Synthesis and antitumor‐promoting activity of benzofuro[2,3‐d]pyridazines fused with 1,2,4‐triazole, 1,2,4‐triazine and 1,2,4‐triazepine

[1]Benzofuro[2,3‐d]pyridazines fused with 1,2,4‐triazole ( 6 and 7 ), 1,2,4‐triazine ( 8–10 ) and 1,2,4‐tri‐azepine (12) were prepared by the ring closure of 4‐hydrazino‐[1]benzofuro[2,3‐d]pyridazine ( 5 ), derived from naturally occurring rotenone. Compounds ( la and lb ) exhibited significant inhibitory activity against 12‐O‐tetradecanoylphorbol 13‐acetate (TPA)‐induced Epstein‐Barr virus early antigen (EBA‐EA) activation in Raji cells. In contrast, the fused [1]benzofuro[2,3‐d]pyridazines except 6c and 8 were quite inactive.     

Carbamoyl Radical‐Mediated Synthesis and Semipinacol Rearrangement of β‐Lactam Diols

In an approach to the biologically important 6‐azabicyclo[3.2.1]octane ring system, the scope of the tandem 4‐exo‐trig carbamoyl radical cyclization—dithiocarbamate group transfer reaction to ring‐fused β‐lactams is evaluated. β‐Lactams fused to five‐, six‐, and seven‐membered rings are prepared in good to excellent yield, and with moderate to complete control at the newly formed dithiocarbamate stereocentre. No cyclization is observed with an additional methyl substituent on the terminus of the double bond. Elimination of the dithiocarbamate group gives α,β‐ or β,γ‐unsaturated lactams depending on both the methodology employed (base‐mediated or thermal) and the nature of the carbocycle fused to the β‐lactam. Fused β‐lactam diols, obtained from catalytic OsO₄‐mediated dihydroxylation of α,β‐unsaturated β‐lactams, undergo semipinacol rearrangement via the corresponding cyclic sulfite or phosphorane to give keto‐bridged bicyclic amides by exclusive N‐acyl group migration. A monocyclic β‐lactam diol undergoes Appel reaction at a primary alcohol in preference to semipinacol rearrangement. Preliminary investigations into the chemo‐ and stereoselective manipulation of the two carbonyl groups present in a representative 7,8‐dioxo‐6‐azabicyclo[3.2.1]octane rearrangement product are also reported.     

Novel five‐membered ring formation by oxidative photocyclization of 4‐(2‐arylvinyl)benzo[a]quinolizinium salts

Oxidative photocyclization of 4‐(2‐arylvinyl)benzo[a]quinolizinium salts ( 6 ) gave five‐ or six‐mem‐bered rings depending on the aryl substituent. The olefins 6a and 6b with a phenyl or naphthyl substituent resulted in a normal six‐membered ring formation to afford 6a‐azoniapicene and 6a‐azoniabenzo[b]picene salts ( 7 and 8 ), respectively. In contrast, the photo‐reaction of pyridyl substituted derivative 6c resulted in novel five‐membered ring formation to yield 3b‐azonia‐5‐(2‐pyridyl)acephenanthrylene salt ( 10 ).     

Two isomeric 2‐[4‐chloro‐2‐fluoro‐5‐(prop‐2‐ynyloxy)phenyl]hexahydro­isoindole‐1,3‐dione compounds

The molecular structures of 2‐[4‐chloro‐2‐fluoro‐5‐(prop‐2‐ynyloxy)phenyl]‐1,3,4,5,6,7‐hexahydro­isoindole‐1,3‐dione, C₁₇H₁₃ClFNO₃, (I), and the isomeric compound 2‐[4‐chloro‐2‐fluoro‐5‐(prop‐2‐ynyloxy)phenyl]‐cis‐1,3,3a,4,7,7a‐hexahydro­isoindole‐1,3‐dione, (II), are, as anticipated, significantly different in their conformations and in the distances between the farthest two atoms. The six‐membered ring of the 1,3,4,5,6,7‐hexahydro­isoindole‐1,3‐dione moiety in (I) adopts a half‐chair conformation. The dihedral angle between the five‐membered dione ring of (I) and the benzene ring is 50.96 (7)°. The six‐membered ring of the cis‐1,3,3a,4,7,7a‐hexahydro­isoindole‐1,3‐dione moiety in (II) adopts a boat conformation. The dihedral angle in (II) between the five‐membered dione ring and the benzene ring is 61.03 (13)°. In the crystal structures, the molecules are linked by C—H⋯O hydrogen bonds and weak π–π interactions. Compound (I) is a much more potent herbicide than (II). The Cl⋯H distances between the farthest two atoms in (I) and (II) are 11.37 and 9.97 Å, respectively.     

由邻苯二胺合成苯并咪唑、喹喔啉以及1-H-2,3－二氢1,5-苯并氮杂卓

A series of benzo-fused heteroaromatic compounds with 5-, 6- and 7-membered tings, such as benzimidazole,quinoxaline and 1H-1,5-benzodiazepine derivatives, were synthesized through condensation reaction of o-pheny1-enediamine with ary1 aldehydes or ketones. The experimental conditions were carefully examined, and the products were characterized by ^1H NMR, ^13C NMR, MS, IR and elemental analyses. In addition, the structure of a benzodiazaepine derivative with 7-membered ring was confirmed by single crystal X-ray diffraction analysis.     

First Approach to Nitrogen‐Containing Fused Aromatic Hydrocarbons as Targets for Organoelectronics Utilizing a New Transformation of O‐Protected Diaryl Methanols

A new concise approach for the construction of heteroatom analogues of polycyclic aromatic benzo[g]quinoline, benzo[b]carbazole, and pyrido[b]carbazole systems via diaryl methanols is described. This transformation involves formation of a central benzene ring fused to two aromatic 5‐ or 6‐membered rings of pyrrole and/or pyridine by using a combination of two aromatic aldehydes, of which at least one contains a ring nitrogen. Analysis of the UV and fluorescent properties, Stokes shifts, quantum yields in solution, and π‐stacking interactions in the crystal structures of the new materials was performed. These polycyclic aromatic compounds show potential as small‐molecule organoelectronic materials.     

Chemical Reactivity of 4,9‐Dimethoxy‐5‐oxo‐5H‐furo[3,2‐g]chromene‐6‐Carboxaldehyde Toward Some Nucleophilic Reagents

The chemical reactivity of 4,9‐dimethoxy‐5‐oxo‐5H‐furo[3,2‐g ]chromene‐6‐carboxaldehyde (6‐formylkhellin) ( 1 ) was studied toward a diversity of nitrogen nucleophilic reagents. Reaction of carboxaldehyde 1 with some primary amines and heterocyclic amines afforded the corresponding Schiff bases. Also, the reactivity of carboxaldehyde 1 was studied toward some hydrazine derivatives, namely 7‐chloro‐4‐hydrazinoquinoline, 3‐hydrazino‐5,6‐diphenyl‐1,2,4‐triazine, N⁴‐phenylthiosemicarbazide, and S‐benzyldithiocarbazate. 6‐Formylkhellin ( 1 ) underwent ring transformation upon treatment with hydroxylamine hydrochloride producing 5‐hydroxy‐4,9‐dimethoxy‐7‐oxo‐7H‐furo[3,2‐g ]chromene‐6‐carbonitrile ( 22 ). Some pyrimidine, [1,2,4]triazolo[4,3‐a ]pyrimidine, tetrazolo[1,5‐a ]pyrimidine, and diazepine derivatives linked benzofuran were efficiently synthesized. Reaction of carboxaldehyde 1 with a variety of 1,4‐binucleophiles produced furochromone‐fused benzodiazepine, pyridotriazepine, benzoxazepine, and benzothiazepine derivatives. Some unsymmetrical thiocarbohydrazones were also synthesized. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

Synthesis of pyrimidinones by action of benzamidine on a benzocycloheptenic β‐keto ester

The synthesis of a polycyclic heterocyclic ring system compound, ethyl 7‐hydroxy‐4‐oxo‐2‐phenyl‐4,5‐dihydro‐3H‐benzo[6,7]cyclohepta[1,2‐d]pyrimidine‐6‐carboxylate was carried out by condensation of benzamidine on diethyl 5,9‐dihydroxy‐7H‐benzo[a]cycloheptene‐6,8‐dicarboxylate, after opening and then closure of the seven membered ring.     

The Photocyclodimers of 2,3‐Dihydro‐2,2‐dimethyl‐4H‐pyran‐4‐one

On irradiation (350 nm) in benzene solution, dihydropyranone 3 affords predominantly (75%) the cis‐anti‐cis HH‐dimer 4 , but in smaller amounts (12%) also dimer 5 , wherein one of the six‐membered rings is trans‐fused to the (central) cyclobutane ring. The constitution and configuration of 5 was fully elucidated by NMR‐analysis. On contact with SiO₂, 5 isomerizes quantitatively to the cis‐anti‐cis HT‐dimer 7 , the structure of which was established by X‐ray crystal‐structure determination.     

Synthesis of 3‐(4‐Oxo‐4H‐quinolizinyl‐3) and 3‐(4‐Oxo‐4H‐pyridino[1,2‐a]pyrimidinyl‐3) substituted lactic acid derivatives

A one‐step ‘ring switching’ transformation of (S)‐3‐[(dimethylamino)methylidene]‐5‐(methoxycarbonyl)tetrahydrofuran‐2‐one ( 4 ) with 2‐pyridineacetic acid derivatives ( 5–7 ) and 2‐aminopyridines ( 8, 9 ) afforded the corresponding 3‐(4‐oxo‐4H‐quinolizinyl‐3)‐ (15–17) and 3‐(4‐oxo‐4H‐pyridino[1,2‐a]pyrimidinyl‐3)‐2‐hydroxypropanoates ( 18, 19 ), respectively.     

Ring transformations of heterocyclic compounds. XXIII. The UV irradiation product of photochromic 2,4,6‐triaryl‐1‐(spiro[2H‐l‐benzopyran‐2,2′‐indoline]‐6‐yl)pyridinium salts ‐ A phenolate betaine or a pyridinium substituted merocyanine dye?

The synthesis of the novel 2,4,6‐triaryl‐1‐(spiro[2H‐1‐benzopyran‐2,2′‐indoline]‐6‐yl)pyridiniumper‐chlorates 4 by reaction of 5 ‐nitrosalicylaldehydes 6 with 1,3,3‐trimethyl‐2‐methyleneindoline ( 7 ) to 6‐nitro‐spiro[2H‐1‐benzopyran‐2,2′‐indolines] 1 , their stannous chloride reduction to the 6‐amino derivatives 8 , followed by a 2,6‐[C₅+N] ring transformation with 2,4,6‐triarylpyrylium perchlorates 9 , is reported. UV irradiation experiments in twenty solvents of different polarity prove their photochromic properties and show that the photochemically generated negative solvatochromic dyes 5 , formed by ring opening of the benzopyran moiety of 4 , are rather merocyanine than pyridinium phenolate betaine dyes.     

3/4‐phenylene bisheterocycles from ring transformation reaction of sydnone derivatives: Synthesis of 3‐[3/4‐heterocyclyl]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones from 3/4‐acetylphenylsydnones and their biological properties

The bifunctional 3/4‐[acetyl]phenylsydnones 1a, 1b were subjected to a one‐pot ring conversion to 3‐[3/4‐acetyl]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones 2a, 2b , which on further bromination yielded the 3‐[3/4‐bromoacyl]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones 3a, 3b . Reaction of these compounds with thiourea yielded the 3‐[3/4‐(2‐aminothiazol‐4‐yl)]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones 4a, 4b . The other thiazole derivatives 5a, 5b–7a, 7b were prepared by using thiosemicarbazide, thioacetamide, and thiobenzamide, respectively. In another reaction of the bromoacetyl compounds ( 3a, 3b ) with 2‐aminopyridine and 2‐aminothiazole, the fused biheterocyclic compounds 3‐[3/4‐imidazo‐[1,2‐a]pyridine‐2‐yl]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones 8a, 8b and 3‐[3/4‐imidazo‐[2,1‐b]‐thiazol‐6‐yl]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones 9a, 9b were obtained. The 3‐[3/4‐(benzofuran‐2‐carbonyl)]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones 10a, 10b were obtained by treatment of compounds 3a, 3b with o‐hydroxy benzaldehyde. Most of these compounds exhibited antifungal activity greater than the reference drugs used. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:50–54, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20255     

5,5‐Dimethyl‐2,8‐diphenyl‐5H‐dibenzo[b,f]silepine: a synchrotron study

The molecule of the title silepine compound, C₂₈H₂₄Si, lies on a crystallographic general position but has almost exact mirror symmetry. The seven‐membered silepine ring has a boat conformation, with a fold angle of 99.99 (9)° between the C—C=C—C stern and the C—Si—C prow. The planes of the phenyl substituents are rotated by 32.23 (6) and 31.80 (7)° out of the planes of the respective fused benzene rings. Similar folded conformations are found for other dibenzo[b,f]silepines, while analogous dibenzo[b,f]borepines, in which the B atom can participate in conjugation, have a more flattened heterocyclic ring.     

3′,4′‐Bis(4‐chloro­phenyl)­spiro­[chroman‐3,5′(4′H)‐isoxazol]‐4‐one

The title compound, C₂₃H₁₅Cl₂NO₃, crystallizes with two independent mol­ecules in the asymmetric unit. The chroman­one moiety consists of a benzene ring fused with a six‐membered heterocyclic ring which adopts a sofa conformation. The five‐membered spiro­isoxazoline ring is in an envelope conformation. The p‐chloro­phenyl rings bridged by the five‐membered ring are nearly perpendicular to each other. The chromanone moiety of one mol­ecule packs into the cavity formed by the p‐chloro­phenyl rings of a second mol­ecule through the formation of C—H?π interactions. The structure is stabilized by weak C—H?O, C—H?Cl and C—H?π interactions.     

A Study on the Intramolecular Mitsunobu Reaction of N6‐(ω‐Hydroxyalkyl)adenines

The cyclization of N ⁶‐(ω‐hydroxyalkyl)adenines with a N⁶H‐group leads to N⁶,N1 ring closure regardless of the method of the cyclization that was used. Five‐membered to eight‐membered rings were obtained using NBS/PPh₃; however, under Mitsunobu conditions, the eight‐membered fused purine was not formed. Surprisingly, the cyclization of N ⁶‐methyl‐N ⁶‐(4‐hydroxybutyl)adenine only leads to N⁶,N7 ring closure using both methods.     

Diversity Oriented Synthesis of Indoloazepinobenzimidazole and Benzimidazotriazolobenzodiazepine from N1‐Alkyne‐1,2‐diamines

A one‐pot protocol for the diversity oriented synthesis of two N‐polyheterocycles indoloazepinobenzimidazole and benzimidazotriazolobenzodiazepine from a common N¹‐alkyne‐1,2‐diamine building block is described. The approach involves sequential formation of benzimidazole through cyclocondensation and oxidation, which is followed by the formation of either an azepine ring (through alkyne activation and 6‐endo‐dig cyclization, 1,2‐migration with ring expansion, and re‐aromatization), or diazepine and triazole rings through 1,3‐dipolar cycloaddition.     

3β,7α,12α‐Tri­formyl­oxy‐24‐nor‐5β‐chol‐22‐ene

The title compound, alternatively called 24‐nor‐5β‐chol‐22‐ene‐3β,7α,12α‐triyl triformate, C₂₆H₃₈O₆, has a cis junction between two of the six‐membered rings. All three of the six‐membered rings have chair conformations that are slightly flattened and the five‐membered ring has a 13β,14α‐half‐chair conformation. The 3β, 7α and 12α ring substituents are axial and the 17β group is equatorial. The 3β‐formyl­oxy group is involved in one weak intermol­ecular C—H⋯O bond, which links the mol­ecules into dimers in a head‐to‐head fashion.