Antitumour polycyclic acridines .1. Synthesis of 7H-pyrido- and 8H-quino-[4,3,2-kl]acridines by Graebe-Ullmann thermolysis of 9-(1,2,3-triazol-1-yl)acridines: application of differential scanning calorimetry to predict optimum cyclisation conditions

被引:48
作者
Hagan, DJ
GimenezArnau, E
Schwalbe, CH
Stevens, MFG
机构
[1] UNIV NOTTINGHAM,DEPT PHARMACEUT SCI,CANC RES LABS,NOTTINGHAM NG7 2RD,ENGLAND
[2] ASTON UNIV,INST PHARMACEUT SCI,BIRMINGHAM B4 7ET,W MIDLANDS,ENGLAND
来源
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 | 1997年 / 18期
关键词
D O I
10.1039/a702299i
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The thermal decomposition of a series of acridines substituted in the 9-position with 1,2,3-triazol-1-yl, benzotriazol-1-yl and naphthotriazol-1-yl groups has been studied by differential scanning calorimetry, Whereas the monocyclic triazole 7a shows a discrete melting endotherm followed by a decomposition exotherm corresponding to formation of the 7H-pyrido[4,3,2-kl]acridine 8, in the benzotriazoles 10a-e and naphthotriazole 10f these processes coincide with a single sharp exothermic transition attributed to cyclisation to polycyclic acridines 11a-f, respectively, The optimum conditions for the preparative scale synthesis of polycyclic acridines from triazole precursors utilised boiling diphenyl ether as the decomposition medium, A benzotriazol-1-ylacridine 10e substituted in the peri position with a methyl group behaved anomalously: as well as affording the expected 8H-quino[4,3,2-kl]acridine 11e, cyclisation also led to radical mediated loss of the methyl group to form the unsubstituted 8H-quino[4,3,2-kl]acridine. 11a and H-abstraction from the methyl group leading to the benzoazepinoacridine 12. Radical cyclisation of 9-(2-iodoanilino)acridine 16 also gave 8H-quino[4,3,2-kl]acridine 11a, The crystal structure of 11a confirms the 8H tautomer arrangement with intermolecular N8-H ... N13 hydrogen bonding and exhibits a polycyclic system that is planar with rms deviation 0.044 Angstrom.
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页码:2739 / 2746
页数:8
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