The chemistry of polycyclic arene imines. III. N-alkylation of phenanthrene 9,10-imineN-alkylation of phenanthrene 9,10-imine

Phenanthrene 9,10-imine ( 1 ) was shown to undergo N-alkylation without aziridine ring cleavage by (a) metallation with sodium methylsulfinylmethide followed by addition of an alkyl halide at −20° (b) reaction of 1 , sodium hydride and the halide in dimethylformamide at 40° (c) treatment of a dichloromethane solution of 1 , the halide and triethylbenzylammonium chloride with aqueous sodium hydroxide under phase transfer conditions. The syntheses of N-isopropyl-, N-butyl-, N-pentyl-, N-allyl- and N-benzylphenanthrene 9,10-imine ( 2–6 ) are described.     

The chemistry of polycyclic arene imines. I. Substitution at the nitrogen atom of 1a,9b-dihydro-1H-phenanthro[9,10-b]azirine

Chlorides of carboxylic, sulfonic and phosphoric acids proved to convert phenanthrene-9,10-imine into the corresponding rearranged acet- sulfon- and phosphonamidophenanthrene. Trimethylchlorosilane and N,O-bis(trimethylsilyl)acetamide reacted with the imine without destruction of the aziridine ring. The silylated compound could be transferred into the respective N-substituted phenanthrene-9,10-imines when treated with acetyl-, methanesulfonyl-, 4-tosyl- and diethylphosphoryl chloride. A remarkably stable N-chlorophenanthrene-9,10-imine was obtained from the unsubstituted compound and N-chlorosuccinimide.     

1a,11b-dihydrobenz[5,6]anthr[1,2-B]azirine. A non k-region polycyclic arene imine

The synthesis of the title compound 9 is described. Benz[a]anthracene 8,9-oxide (6) was reacted with sodium azide in aqueous acetone and the trans-9-azido-8,9-dihydrobenz[a]anthr-8-ol (7), so formed, was cyclized by tri-n-butylphosphine. Attempts to dehydrogenate 10,11-dihydrobenz[a]anthracene 8,9-imine (4) with DDQ or by allylic bromination followed by base assisted dehydrobromination was unsuccessful. The N-tosyl derivative of 4, prepared from the free imine, N,O-bis(trimethylsilyl)acetamide and tosyl chloride underwent rapid aziridine-ring cleavage by the silylating agent to give trans-8,9,10,11-tetrahydro-8-(4-methyl)benzensulfon-amido-9- [(trimethyl)oxy]benz[a]anthracene (10).     

The chemistry of polycyclic arene imines. II. Photochemistry of phenanthrene 9,10-imine and of its N-butyl derivative

The uv irradiation of phenanthrene 9, 10-imine has been shown to give 9H-tetrabenzo[a, c, g, i]carbazole as the major photo-product both in argon purged acetone and in dichloromethane. Phenanthrazine, N-9-phenanthrenyl-9-phenanthrenamine and phenanthrene were formed in smaller quantities. 9-Phenanthrenamine was found to be a minor by-product. N-Butylphenanthrene 9, 10-imine yielded under similar conditions phenanthrene and N-butyl-9-phenanthrenamine as the only isolable polycyclic compounds. In the presence of air the substituted imine gave mainly 2-propylphenanthro[9, 10-d]oxazole.     

The chemistry of polycyclic arene imines. V. Reactions of phenanthrene 9,10-imine with nucleophiles under phase transfer conditions

Reactions of phenanthrene 9,10-imine (1) with alkyl halides, sodium azide and ammonium thiocyanate in two liquid phase systems were investigated. In the presence of aqueous sodium hydroxide and alkyl halides triethylbenzylammonium (TEBA) salts promote N-alkylation of 1 with preservation of the aziridine ring. Tetrabutylammonium (TBA) salts catalyze nucleophilic substitutions in which the three membered ring is cleaved. Aqueous sodium azide reacts with 1 to give trans-10-azido-9,10-dihydro-9-phenanthrenamine (2) . Ammonium and potassium thiocyanate cause expansion of the aziridine ring; while the unsubstituted imine 1 yields the 2-thiazolamine derivative 4 , N-butylphenanthrene 9,10-imine (8) froms trans-3a,11b-dihydro-3-butylphenanthro[9,10-d]thiazol-2-imine (9) with an exocyclic CN bond. The structure of 9 was established by X-ray crystal analysis.     

The chemistry of polycyclic arene imines. VII. Reactions of phenanthrene 9,10-imine with aromatic carboxaldehydes,carboxylic acids and acetylenic esters

The reactions of phenanthrene 9,10-imine ( 1 ) with aromatic aldehydes, benzoic acids and acetylenedi-carboxylic esters were investigated. The aldehydes were shown to give 1-[N-(arylmethylidene)-9-phenanthreneamine-10-yl]-1a,9b-dihydrophenanthro[9,10-b]azirine 2. The ‘dimeric’ structure of these products was established by X-ray diffraction analysis. The carboxylic acids proved to form in the presence of dicyclohexylcarbodiimide, N-aroylphenanthrene 9,10-imines 7 , that readily undergo rearrangement to N-aroyl-9-phenanthrenamines 8. Esters of acetylenedicarboxylic acid gave the corresponding esters of (Z)-2-(1a,9b-dihydrophenanthro[9,10-b]azirine-1-yl)-2-butendioic acid 10 .     

Arene imine derivatives of chrysene and of benzo[g]chrysene: 1a,11c-dihydrochryseno[5,6-b]azirine and 1a,13c-dihydrobenzo[11,12]chryseno[5,6-b]azirine

The syntheses of the K-iraines (which are also benzo-bay-region derivatives) of chrysene ( 1 ) and benzo[g]-chrysene ( 2 ) are described. The preparation of 1a,11c-dihydrochryseno[5,6-b]azirine ( 5 ) was accomplished by treatment of 1a,11c-dihydrochryseno[5,6-b]oxirene ( 4 ) with sodium azide, and the mixture of trans-azido-alcohols 6 and 7 , so formed, was either cyclized with triethyl phosphite, or converted into E-6-azido-5-chloro-5,6-dihydrochrysene ( 8 ) followed by lithium aluminium hydride reduction. The synthesis of 1a,13c-dihydrobenzo-[11,12]chryseno[5,6-b]azirine ( 12 ) included the transformation of the corresponding oxide 11 into a mixture of E-9-azido-9,10-dihydrobenzo[g]chrysen-10-ol ( 13 ) and E-10-azido-9,10-dihydrobenzo[g]chrysen-9-ol ( 14 ), and reaction with tri-n-butylphosphine to give a mixture of Staudinger adducts 15 and 16 that underwent thermal decomposition into 12 upon heating in boiling dichloromethane.     

Derivatives of benzo[4,5]cyclohepta[1,2-b]thiophene. 4. Synthesis of 1-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yl)-3-alkylaminoazetidines

Thirteen 1-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yl)-3-alkylaminoazetidines 11 have been synthesized in three steps from 4-amino-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophene ( 6 ), which was obtained from the reduction of either 4-azido 4 or 4-hydroxyimino 5 derivatives. All the compounds have been evaluated as potential antidepressive agents.     

Synthesis and photopinacol rearrangement of 1a,9a-dihydro-1a,9b-diphenylphenanthro[9,10-b]oxirene

The synthesis of the title compound is described. Pinacol reduction of 2,2′-dibenzoylbiphenyl followed by dehydration of the trans-diol, so formed, with dimethylformamide dimethyl acetal yielded 55% of the oxirane. Irradiation of the oxide in methylene chloride at 254 nm gave 10,10-diphenyl-9-(10H)phenanthrone as the major photoproduct.     

p-(1H-phenanthro[9,10-d]imidazol-2-yl)- substituted calix[4]arene, a deep cavity for guest inclusion

The reaction of tetra-p-formyltetra-O-propylcalix[4]arene with phenanthrenequinone in the presence of NH(4)OAc affords compound 2, a new class of calixarene with an expanded aromatic cavity, that could be stabilized by hydrogen-bonded bridges and/or ion pairing, thus preventing collapse into fully stacked pinched cone conformations as depicted. Two partially protonated calixarenes interdigitate in the solid state to give rise to a self-assembled face-to-face dimer, stabilized by pi-pi stacking interactions.     

Further studies on heterocyclic arene imines. Preparation of 1a,9b-dihydroazirino[f][1,7]phenanthroline, 3b,4a-dihydroazirino-[2,3]phenaleno[1,9-g,h]quinoline and 1a,13b-dihydrodibenzo[1,2:6,7]phenazino[1,2-b]azirine

The syntheses of the K-imine derivatives of 1,7-phenanthroline, phenaleno[1,9-g,h]quinoline, and dibenzo[a,h]phenazine are described. The parent heterocyclic compounds 4, 9 and 14 were oxidized to the corresponding K-oxides, 5, 10 and 15 , which in turn were reacted with sodium azide in aqueous acetone. The resulting trans-azido alcohols were then cyclized with tributylphosphine to the title compounds 6, 11 and 16 .     

N,N-二[4-(9H-9-咔唑基)苯基]-3,5-二溴苯胺的合成

以3,5-二溴苯胺,碘苯和咔唑为原料,经取代和Ullmann反应合成了一个新的含咔唑三苯胺化合物——N,N-二[4-(9H-9-咔唑基)苯基]-3,5-二溴苯胺,其结构经1H NMR,13C NMR和ESI-MS表征。     

Polycyclic arene sulfides. Preparation of 1a,2,3,11b-tetrahydrobenz-[5,6]anthra[1,2-b]thiirene, 6b,7a,8,9-tetrahydrobenzo[10,11]-chryseno[1,2-b]thiirene,and 7,8,8a,9a-tetrahydrobenzo-[10,11]chryseno[3,4-b]thiirene

The title compounds 5, 7 and 9 which are the first arene sulfides of 7,8-dihydrobenz[a]anthracene, 8,9-and 10,11-dihydrobenzo[a]pyrene, respectively, have been synthesized by treatment of the corresponding arene oxides 4, 6 and 8 with N,N-dimethylthioformamide in the presence of catalytic amounts of trifluoroacetic acid.     

2,3,4,9-Tetrahydro-1H-pyrido[3,4-b]indoles. II. Reversible transformation of 1-alkyl-2-(4,9-dihydro-3H-pyrido[3,4-b]indol-1-yl)cyclohexanol into 1-alkylidene-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoles

Treatment of 2-(4,9-dihydro-3H-pyrido[3,4-b]indol-1-yl)-1-methylcyclohexanol ( 2a ) with acetic anhydride or methyl isocyanate gave 2-acetyl-2,3,4,9-tetrahydro-1-(6-oxoheptylidene)-1H-pyrido[3,4-b]indole ( 3 ) or 1,3,4,9-tetrahydro-N-methyl-1-(6-oxoheptylidene)-2H-pyrido[3,4-b]indole-2-carboxamide ( 4 ), respectively. Simpler analogues, 1-alkyl-4,9-dihydro-3H-pyrido[3,4-b]indoles, 7 , subjected to identical reaction conditions, gave 2-acetyl-1-alkylidene-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoles 8 and 1,3,4,9-tetrahydro-N-methyl-1-alkyli-dene-2H-pyrido[3,4-b]indole-2-carboxamides 9 , respectively. A limited lanthanide shift reagent study to determine stereochemical assignments was also performed.     

Synthesis and autoxidation of new tetracyclic 9H,10H-indolizino[1,2-b]indole-1-ones.

The new tetracyclic 9H,10H-indolizino[1,2-b]indole-1-one derivatives (7a-d, 7ea, 7eb) have been synthesized by modified Fischer indole synthesis from the enol ether of 2,5-dihydroxy-7-methyl-6-cyano-indolizine (3) and arylhydrazines (4a-g). Attempted N-methylation of 7a-d produced a series of autoxidized products including 10-hydroperoxy-1-methoxyindolizino[1,2-b]indole (9a-d) as the major product accompanied with methylperoxides (10a-d and 11a-d) and 2-formyl-3-(pyridine-2-yl)indole (12a, 12c) derivatives as the minor products. A plausible mechanism of the autoxidation is postulated based on the isolation of some intermediates. The reaction is thought to proceed through azaenolate/enamine intermediates following a novel type of autoxidation.     

A modified bischler-napieralski reaction. Synthesis of 2,3,4,9- tetrahydro-1H-pyrido[3,4-B]indole derivatives and their base-catalyzed transformation to N-acetyl-N-[2-[1 -acetyl-2-[1 -(acetyloxy)-1-propenyl]- 1H-indol-3-yl]ethyl]acetamides

The treatment of N-[2-(1H-indol-3-yl)ethyl]alkanamide, 1 (1), with phosphorus oxychloride under controlled conditions gave l-alkyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-ol, 2 . The reaction of 2 with acetic anhydride or with methyl isocyanate at room temperature resulted in the formation of amido carbinol 3 and urea carbinol 7, respectively. The former was transformed into amido ester 4 by boiling acetic anhydride. When the reaction of 3 with acetic anhydride was carried out in the presence of excess triethylamine at 105°, C-N bond cleavage of the tetrahydropyridine ring took place with concurrent bis(N-acetylation) to give the enol ester derivative 5 . The structures of all compounds are consistent with chemical and spectral evidence.     

Synthesis of representative 10-aryl-, 10-aralkyl- and 10-heteraryl-9H-naphtho[1′,2′:4,5]thiazolo[3,2-b]- [1,2,4]triazin-9-ones as potential anti-HIV agents

To prepare the title compounds, cyclocondensation of 1-amino-2-iminonaphtho[1,2-d]thiazole ( 2 ) with some representative glyoxylic acid derivatives was investigated. Heating 2 with methyl phenylglyoxylate ( 3a ) in methanol afforded only the open chain intermediates 4a,b . However, when this reaction was performed in re-fluxing glacial acetic acid, the expected compound, 10-phenyl-9H-naphtho[1′,2′:4,5]thiazolo[3,2-b][1,2,4]- triazin-9-one ( 5a ) was produced in 27% yield. Similar treatment of 2 with benzyl-, 2-furyl- and 2-thienylgly-oxylic acids 3b-d gave the corresponding 10-benzyl-, 10-(2-furyl)- and 10-(2-thienyl)-9H-naphtho[1′,2′:4,5]thi-azolo[3,2-b][1,2,4]triazin-9-ones 5b-d in 48–67% yields. As by-products, 9-benzoyl- and 9-(2-thenoyl)naphtho-[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazoles 6a,d were also isolated. Compound 5a was selected for in vitro anti-HIV evaluation but found to be inactive.     

Approaches to 1H-Cyclopropa[l]phenanthrenes. Eliminations with 1a,9b-Dihydro-1H-cyclopropa[l]phenanthrene Derivatives

Base-induced elimination of the sulfonium salt 2i in the presence of furan affords the addition products 7 and 8 , derived from 1H-cyclopropa[l]phenanthrene ( 1 ) and the isomeric cyclopropene 5a (Scheme 3). Upon oxidation, the selenide 2c yields phenanthrene-9-methanol ( 9 ), presumably via 1 . No evidence for the intermediate 1 is obtained from sulfoxide pyrolysis with 2e , which leads to products formed by radical pathways (Scheme 5). Reductive elimination of the disulfone 3b gives half-reduction to monosulfone 2g and complete reduction to cyclopropane 2 as well as 9-methylphenanthrene ( 15 ), but no evidence for the intermediate 1 .     

1,1-Disubstituted-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indolecarboxylic acid esters and ketones. The base catalyzed transformation of 1-(2′,3′,4′,9′-tetrahydrospiro[cyclohexane-1,1′-[1H]pyrido[3,4-b]indol]-2-yl)alkanones into 2-(4,9-dihydro-3H-pyrido[3,4-b]indol-1-yl)-1 -alkylcyclohexanols

Condensation of 1H-indole-3-ethanamines 1 with cyclic β-keto esters 2 under azeotropic conditions followed by acid-catalyzed ring closure of the resulting enamines 3 gave 2′,3′,4′,9′-tetrahydrospiro[piperidine-3,1′,-[1H]pyrido[3,4-b]indole] -4-carboxylic acid alkyl esters 4 . Condensation of 1 with 2-acylcycloalkanones 8 gave two types of enamines, 10 and 11 , respectively. Enamines 10 on treatment with acid gave 1-(2′,3′,4′,9′-tetrahydro-3H-pyrido[3,4-b]indol-1-yl)-1-alkylcyclohexanols 17 . Compounds 17 were further dehydrated to give cycloalkane derivatives 19.