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.     

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.     

Synthesis and Properties of 2-(2-Furyl)- and 2-(2-Thienyl)-1-methylphenanthro[9,10-d]imidazoles

Condensation of 9,10-phenanthrenequinone with 2-furaldehyde and 2-thiophenecarbaldehyde in glacial acetic acid in the presence of ammonium acetate gave 2-(2-furyl)- and 2-(2-thienyl)phenanthro[9,10-d]imidazoles which were converted into the corresponding 1-methyl derivatives. The furan and thiophene rings in the products lose their acidophobic properties. Depending on the conditions, electrophilic substitution reactions in 2-(2-furyl)- and 2-(2-thienyl)phenanthro[9,10-d]imidazoles occur both at the furan (thiophene) and phenanthrene moieties.     

Die molekulare und kristalline Struktur von 9,10-Dihydro-4-(3-dimethylamino-propyliden)-4H-benzo[4,5] cyclohepta[1,2-b]thiophen-hydrochlorid. Untersuchungen über synthetishe Arzneimittel, 19. Mitteilung [1]

The α-isomer of 9,10-dihydro-4-(3-dimethylamino-propylidene)-4 H-benzo[4,5] cyclohepta [1, 2-b] thiophen is shown to have the trans configuration by means of an X-ray analysis of its hydrochloride.     

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.     

Degenerate Rearrangement of Long-Lived 9,10-Dimethyl-9-(cis-1-methyl-1-propenyl)phenanthrenium Ion: 1,2-Shift of the Dimethylvinyl Group

Dynamic NMR study showed that 9,10-dimethyl-9-(cis-1-methyl-1-propenyl)phenanthrenium ion generated by reaction of 1,2,2a,10b-tetramethyl-2a,10b-dihydrocyclobuta[l]phenanthrene with HSO3F below -100°C undergoes very fast (G = 22 kJ/mol at -120°C ) degenerate 1,2-shift of the dimethylvinyl group.     

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 .     

The chemistry of arene imines. IV. An unusual silver promoted transformation of N-chlorophenanthrene 9,10-imine into 9,10-phenanthrenequinone dialkyl acetals

Methanolic silver nitrate and perchlorate convert N-chlorophenanthrene 9,10-imine (1) into 10,10-dimethoxy-9(10H)-phenanthrone (2) in 60% yield. Substitution of the mthanol by ethanol, 1- and 2-propanol gives phenanthrenequinone diethyl-, di-1-propyl- and di-2-propylacetals (3-5) , respectively. Silver acetate promotes these transformations only in the presence of a protic acid. The reaction mechanism is assumed to involve the generation of a cyclic nitrenium ion, nucleophilic ring opening by methanol, hydrolysis of the imine function and silver ion promoted oxidation.     

Syntheses and bioactivities of substituted 9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrones. Unusual reactivities with amines

A number of substituted 9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrones have been synthesized and their anticancer and antimalarial activities evaluated. A one-pot synthesis of 2,5,8-trimethoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4-dione (4) was achieved by heating a mixture of 1,4-dimethoxyanthracene, methoxyhydroquinone, silver oxide, and zinc iodide in toluene. Regioselective bromination of 4 and 2-methoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone (7) with N-bromosuccinimide provided 2-bromo-3,5,8-trimethoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4-dione and 2-bromo-3-methoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone (1), respectively. The reactions of 1 with aliphatic primary amines and secondary amines, respectively, produced different products, a result most likely attributed to the different basicities (or nucleophilicities) and steric effects of the two kinds of amines. The structure of the displacement product, 2-bromo-3-[2-(tert-butoxycarbonyl)ethylamino]-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone, from the reaction of 1 with tert-butyl 3-aminopropanoate was unequivocally determined by a single-crystal X-ray analysis. IC(50) values of triptycene bisquinones for the inhibition of L1210 leukemia cell viability are in the 0.11-0.27 microM range and for the inhibition of Plasmodium falciparum 3D7 are in the 4.7-8.0 microM range.     

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 .     

Substitution reactions of phenanthro[9,10-d]triazole with benzyl chlorides

The reaction of the potassium salt of phenanthro[9,10-d]triazole and benzyl chloride gave 2-(benzyl)-2H-phenanthro[9,10-d]triazole ( 2a ) in 15% yield. The other regio-isomer, 1-(benzyl)-1H-phenanthro[9,10-d]-triazole ( 1a ), was obtained as a by-product in 3.9% yield. Similar reactions with benzyl chlorides having a methyl, a chloro or a nitro group on the aromatic ring gave the corresponding two products, 1b-j and 2b-j . In all cases, 2b-j were major products in yields of 14–62%, 1b-j were minor ones in yields of 1.4–7.6%. The structures of the isomers were confirmed by X-ray crystal analyses.     

离子液体[TEAPS]HSO_4催化“一锅法”合成2-取代-1H-菲并[9,10-d]咪唑

在室温离子液体3-(三乙胺基)丙磺酸硫酸氢盐([TEAPS]HSO4)的催化作用下,由菲醌、醋酸铵和芳香醛"一锅法"合成了一系列2-取代-1H-菲并[9,10-d]咪唑化合物.实验中考察了投料比、催化剂用量、溶剂、反应时间对反应的影响,确定了最优反应条件,给出了可能的反应机理.此外催化剂可以方便的回收,且循环使用四次其催化活性并没有显著降低.目标产物经过了1HNMR,13CNMR,IR和MS确证表征.条件温和,反应时间短,产率高,且对环境友好.     

Condensed 1,2,4-Triazines I: Behaviour of Phenanthro[9,10-e]-1,2,4-triazine Derivatives Towards Alkylating and Reducing Agends,Grignard Reagents,and Amines

Alkylation of 3-hydroxy-phenanthro[9,10-e]1,2,4-triazine ( 1a ) yielded the N(2)-alkyl derivatives 2a – 2b ; alkylation of the 3-mercapto analogue 1b yielded the S-alkyl derivatives 1f – 1i . 1a – 1b reacted with alkyl and aralkylmagnesium halides to yield the corresponding 3-hydroxy-, and 3-mercapto-5-alkyl-(aralkyl)-phenanthro[9,10-e]2,3,4,5-tetrahydro-1,2,4-triazines 5a – 5f . Reduction of 1a yielded the hexahydrotriazine derivative 7 . Amination of 1c yielded the 3-amino derivatives 1j – 1o after prolonged heating.     

Structure elucidation of [1,3]oxazolo[4,5‐e][2,1]benzisoxazole and naphtho[1,2‐d][1,3]‐ and phenanthro[9,10‐d]oxazoles using gradient selected gHMBC,gHMQC and gHMQC‐TOCSY NMR techniques

Structure elucidation of compounds in the benzisoxazole series ( 1 – 6 ) and naphtho[1,2‐d][1,3]‐ ( 7 – 10 ) and phenanthro[9,10‐d][1,3]oxazole ( 11 – 14 ) series was accomplished using extensive 2D NMR spectroscopic studies including ¹H–¹H COSY, long‐ range ¹H–¹H COSY, ¹H–¹³C COSY, gHMQC, gHMBC and gHMQC‐TOCSY experiments. The distinction between oxazole and isoxazole rings was made on the basis of the magnitude of heteronuclear one‐bond ¹J_{C2, H2} (or ¹J_{C3, H3}) coupling constants. Complete analysis of the ¹H NMR spectra of 11 – 14 was achieved by iterative calculations. Gradient selected gHMQC‐TOCSY spectra of phenanthro[9,10‐d][1,3]oxazoles 11 – 14 were obtained at different mixing times (12, 24, 36, 48 and 80 ms) to identify the spin system where the protons of phenanthrene ring at H‐5, H‐6 and at H‐9 and H‐7 and H‐8 were highly overlapping. Copyright © 2003 John Wiley & Sons, Ltd.     

Transformations of 1-amino-2-(3-hydroxyalk-1-ynyl)-9,10-anthraquinones in the presence of amines

When heated in piperidine, 1-amino-2-(3-hydroxyalk-1-ynyl)-9,10-anthraquinones undergo cyclization into 2-(1-hydroxyalkyl)naphtho[2,3-g]indole-6,11-diones. In contrast, 1-amino-2-(3-hydroxy-3-phenylpropynyl)-9,10-anthraquinone reacts with primary and secondary amines to give the corresponding 1-amino-2-(1-amino-2-benzoylvinyl)-9,10-anthraquinones, which undergo cyclization into 4-dialkylamino- or 4-alkylamino-2-phenylnaphtho[2,3-h]quinoline-7,12-diones. Heating of the starting phenylpropynol with Et₃N causes its dehydrogenation and isomerization.     

Synthesis and properties of 2-(2-furyl)-1-methyl-1H-acenaphtho[9,10-d]imidazole

2-(2-Furyl)-1-methyl-1H-acenaphtho[9,10-d]imidazole was obtained by the condensation of 9,1-acenaphthenequinone with furfural in the presence of ammonium acetate followed by N-methylation of the obtained 2-(2-furyl)-1H-acenaphtho[9,10-d]imidazole with methyl iodide in N-methylpyrrolid-2-one in the presence of potassium hydroxide. It was established that its electrophilic substitution in an acidic medium only takes place at position 2 of the furan ring while in a neutral medium both position 2 and position 7 of the aromatic part of the molecule undergo electrophilic attack. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 191–196, February, 2006.     

Reaction of 1-amino-2-phenylethynyl-and 2-acylethynyl-1-amino-9,10-anthraquinones with HNO2. Synthesis of 1H-3-acylnaphtho[2,3-g]indazole-6,11-diones

The reactions of 1-amino-2-phenylethynyl-and 2-acylethynyl-1-amino-9,10-anthraquinones with HNO₂ in a mixture of dioxane and a mineral acid at 20 °C were studied. Under these conditions, 2-alkynyl-1-amino-9,10-anthraquinones, irrespective of the structure of the C=CR substituent, are cyclized into 3-substituted 1H-naphtho[2,3-glindazole-6,11-diones. The nature of the acetylenic group in the initial compound and the choice of the mineral acid determine the structure of the substitutent in position 3 of the product (1,1-dichloroalkyl or acyl) but have no effect on the regiospecificity of cyclization. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 110–114, January, 1997.     

Synthesis and transformations of 2-(2-furyl)- and 2-[β-(2-furyl)vinyl] phenanthr [9,10]imidazoles

The corresponding 2-(2-furyl)- and 2-[-(2-furyl)vinyl] phenanthr[9,10]imidazoles were obtained by the condensation of 9,10 phenanthrenequinone with furfural, -(2-furyl)acrolein, and their 5-bromo and 5-nitro derivatives in the presence of ammonium acetate in glacial acetic acid. Their metallation, acetylation, nitration, and replacement of halogen by a nitro group were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1014–1016, August, 1971.     

Alkaline condensation of 9,10-phenanthrenedione with N,N-dialkylguanidines. A novel synthesis of 2′-(dialkylamino)spiro[9H-fluorene-9,4′-[4H]imidazol]-5′(3′H)ones

9,10-Phenanthrenedione was reacted with equimolar amounts of N,N-dimethylguanidine or creatine in 0.2 N potassium hydroxide in ethanol-water, 7:3 to obtain 2′-(dimethylamino)spiro-[9H-fluorene-9,4′-[4H]imidazol]-5′(3′H)one or N-(3′,5′-dihydro-5′-oxospiro[9H-fluorene-9,4′-[4H]imidazol]-2′-yl)-N-methylglycine, respectively. These products are the first derivatives of this ring system with 2′-amino substituents. Formation of these products accounts for the previously reported absence of fluorescence when 9,10-phenanthrenedione reacts with N,N-di-substituted guanidines.     

Photoalkylation of phenanthro[9,10-d] oxazole

The photochemical reaction of phenanthro[9,10-d]oxazole with ethanol, 1-propanol, 2-propanol, or diethyl ether resulted in the substitution of the 1-and/or 2-hydroxyalkyl and/or alkyl groups at the position 2.