5,12-Diacylated-5,6,11,12-tetrahydrodibenzo[b,f][1,4]-diazocines and related compounds

Both N,N′ -(o-phenylene)diformamide (1) and N,N′ -(4-chloro-1,2-phenylene)diformamide (30) reacted with α,α-dibromo-o-xylene (2) in DMF at 95–100° to give 5,6,11,12-tetrahydrodibenzo-[b,f][1,4]diazocine-5,12-dicarboxaldehyde (3a) and the corresponding 2-chloro derivative (3b). With potassium hydroxide in ethylene glycol at 110°, 3a and 3b were selectively saponified to the 5-carboxaldehyde derivatives (4) and either 21a or 22a. Reacylation of the latter led to a series of 5,12-unsymmetrically diacylated derivatives, 5–18. Additionally, 4 was subjected (a) to a basecatalyzed addition to acrylonitrile to give the 12-cyanoethyl derivative (19) and (b) alkylation with α-bromotoluene to give the 12-benzyl compound (20). Saponification of both carboxaldehyde groups in 3a,b required potassium hydroxide in ethylene glycol at 135° and gave the N,N′ -unsubstituted heterocycles (23 and 24) ; these were subsequently reacted with several aldehydes to yield the 5,12-methano derivatives (25–29) .     

Reactions ofo-tosylaminobenzaldehyde withp-aminobenzenesulfonamides. Synthesis and structures of 13-(4-aminosulfonylphenyl)-6,12-epimino-5,11-ditosyl-5,6,11,12-tetrahydrodibenzo[b,f]-1,5-diazocine and itsN-substituted derivatives

The reactions ofo-tosylaminobenzaldehyde (1) withp-aminobenzenesulfonamides (2a-c) yielded 13-(p-RNHSO₂C₆H₄)-6,12-epimino-5,11-ditosyl-5,6,11,12-tetrahydrodibenzo[b f]-1,5-diazocines (3a-c) (R=H (a); 2-thiazolyl (b); or 2,6-dimethoxy-4-pyrimidinyl 2,6-dimethoxy-4-pyrimidinyl (c). The structure of compound3c was confirmed by X-ray diffurction study. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2035–2039, November, 1997.     

二苯并[b,f][1,5]二氮杂芳辛四烯衍生物的合成及拆分

以邻氨基二苯甲酮为原料,经自身缩合环化合成了3种二苯并[1,5]二氮杂芳辛四烯衍生物(1a~1c);以邻苯二甲酸酐和溴苯为原料经傅-克反应制得中间体2-(4-溴苯甲酰溴)苯甲酸(M1);M1经叠氮化后自缩合制得6,12-二(4-溴苯基)二苯并[b,f][1,5]二氮杂环辛四烯(1d);以邻氨基苯甲酸甲酯为原料,经自身缩合环化制得中间体二苯并[b,f][1,5]二氮杂环辛四烯-6,12(5H,11H)-二酮(M2);M2经氯化合成6,12-二氯二苯并[b,f][1,5]二氮杂环辛四烯(1e),化合物1a~1e的结构经~1H NMR,~(13)C NMR和ESI-MS表征,其中化合物1c为新化合物。利用超临界色谱(SFC)技术对化合物1a~1e实现了手性拆分,获得5对具有高旋光度的光学活性异构体(ee99%)。     

A Joint Theoretical and Experimental Insight into the Electronic Structure of Chromophores Derived from 6H,12H‐5,11‐Methanodibenzo[b,f][1,5]diazocine

We report on the synthesis and electronic spectra of the chiral, donor‐acceptor (push‐pull) chromophores (±)‐ 4 and (±)‐ 5 with a 6H,12H‐5,11‐methanodibenzo[b,f][1,5]diazocine scaffold (Scheme 1 and Fig. 2). The electronic structures of these compounds were investigated at a quantum‐chemical level (Figs. 2 and 3). The chemical reactivity of 6H,12H‐5,11‐methanodibenzo[b,f][1,5]diazocine ((±)‐ 11 ) towards aromatic electrophilic substitution (Scheme 2 and Table) provided additional information about its electronic structure and confirmed nonnegligible delocalization of the lone pair of the bridge‐head N‐atoms in this heterocyclic system.     

A rapid and efficient access to diaryldibenzo[b,f][1,5]diazocines

2-Benzoylbenzoyl azides undergo facile cyclization under acidic conditions to give substituted dibenzo[b,f][1,5]-diazocines in good yields. This approach shortens the synthetic steps toward these compounds as compared with conventional methods. The mechanism of the diazocine synthesis is assumed to proceed by an unprecedented intermolecular [2 + 2] cyclization.     

A facile synthesis of 2,4,8,10-tetrahalo-6,12-diaryldibenzo[b,f][1,5]diazocines

3,5-Dihalo-2-aminobenzophenones 2 on prolonged reflux in dry pyridine gave 2,4,8,10-tetrahalo-6,12- diaryldibenzo[b,f][1,5]diazocines 3 in high yields. Attempted condensation of 2 with glycine ester hydrochloride under identical reaction conditions failed to afford 1,4-benzodiazepines.     

Synthesis of 2- and 3-substituted-1,2,3,4-tetrahydrodibenzo[f,h]isoquinolines

Some 2- and 3-substituted-1,2,3,4-tetrahydrodibenzo[f,h]isoquinolines were prepared by a synthetic scheme involving a selective Borch reduction of an amide to the corresponding amine and a Friedel-Crafts cyclization to obtain the dibenzo[f,h]isoquinoline system. The title compounds, which have a similarity to the cell growth inhibitory alkaloid cryptopleurine, failed to exhibit significant protein synthesis inhibitory activity.     

The synthesis of cis-6,12-Diaryl-6H,12H-dibenzo[b,f][1,5]dithiocin-6,12-imine and cis-6,12-Diphenyl-6,12-epoxy-6H,12H-dibenzo[b,f][1,5]dithiocin

When treated with concentrated hydrochloric acid or heated beyond its melting point, the versatile thioimine 2 2-mercaptobenzhydrylidenamine was unexpectedly converted to the title ring system. Also, this imine can be converted to 3-phenyl-1,2-benzisothiazoles by prolonged exposure to air.     

Synthesis and Ring Opening Reactions of Tetrahydroimidazo[1,5- b ][1,2,4]oxadiazol-2(1 H )-thiones

1,3-Dipolar cycloaddition of imidazoline 3-oxides 1 with methylisothiocyanate proceeds regio- and diastereoselectively to give tetrahydroimidazo[1,5- b ][1,2,4]oxadiazol-2(1 H )-thiones 3 in high yields. The cis configuration of the adducts were proved by our double cis elimination test as well as by NOESY experiments. The imidazooxadiazol-2-thiones 3a-e were treated with concentrated HCl in ethanol at 50°;C to give the corresponding 4 H -[1,2,4]oxadiazole-5-thione only in the cases where the substituent at C-6 is an aryl.