Development of Novel Aromatic Nucleophilic Substitutions and Its Applicafion to the Highly Efficient Synthesis of Biologically Active Fluorine-Containing Heterocycles

4-二甲氨基喹啉与N-三氟乙酰基吡啶盐进行三氟乙酰化反应，高产率地合成了3-三氟乙酰基-4-二甲氨基喹啉1。以8-二甲氨基喹啉和三氟乙酸酐为原料，合成了5，7-二(三氟乙酰基)-8-二甲氨基喹啉-2。1-二甲氨基萘的二酰化反应和随后的区域选择性脱酰化反应相结合，以较高的产率合成了新的含氟砌块--2-三氟乙酰基-1-二甲氨基萘3。发现新的底物1-3与N-、S-、O-亲核试剂发生了新的芳香族亲核取代反应，高产率地得到了相应的N-N、N-S和N-O交换产物。通过1与双官能团亲核试剂的芳香亲核取代反应和随后的环化反应，可以很容易地合成新的含氟杂环化合物，如吡唑、异恶唑、二氮杂卓、二苯并并吡喃并喹啉和苯并喹啉。3-三氟乙酰基-4-氨基喹啉、氨水和醛、酮三组分的环合反应，以较高的产率得到了相应的含氟嘧啶喹啉和苯并菲。3-三氟乙酰基-4-二烷基氨基喹啉经酸催化的恶嗪成环反应，以较高的产率合成了含氟恶嗪喹啉类化合物。底物2很容易与1，2-二胺和羟胺反应，高产率地合成相应的含氟1，4-二氮杂喹啉和异恶唑喹啉。通过3与双官能团亲核试剂的芳香族亲核取代反应和分子内环合反应，高效地合成了含三氟甲基的苯并吖啶类、苯并喹啉类和苯并硫杂杂菲类化合物。

Trifluoroacetylation of 4-dimethylaminoquinoline with N-trifluoroacetylpyridinium salts gave 3-trifluoroacetyl-4-dimethylaminoquinoline 1 in good yields. 5,7-Bis (trifluoroacetyl)-8-dimethylaminoquinoline 2 was easily prepared by the reaction of 8-dimethylaminoquinoline with trifluoroacetic anhydride. The combination of diacylation reaction and the following regioselective deacylation reaction of 1-dimethylaminonaphthalene provided new fluorine-containing building block, 2-trifluoroacetyl-1-dirnethyaminonaphthalene 3 in good yields. It was found that new substrates 1-3 underwent novel aromatic nucleophilic substitution reactions with N-, S-, O-nucleophiles to give the corresponding N-N, N-S and N-O exchanged products in high yields.New fluorine-containing heterocyclic compounds such as pyrazoles, isoxazoles, diazepines, dibenzonaphthyridines, benzothiopyranoquinolines and benzoquinolines were readily synthesized by the novel aromatic nucleophilic substitutions of 1 with bifunctional nucleophiles and the subsequent cyclization reactions. The three components cyclocondensation reactions of 3-trifluoroacetyl-4-aminoquinoline, ammonia water and aldehydes or ketones afforded the corresponding fluorine-containing pyrimidoquinolines and benzonaphthyridines in excellent yields. 3-Trifluoroacetyl-4-dialkylaminoquinoline underwent acid-catalyzed oxazine-ring formation reactions to give fluorine-containing oxazinoquinolines in good yields. Substrate 2 easily reacted with 1,2-diamines and hydroxylamines to afford the corresponding fluorine-containing 1,4-diazepinoquinolines and isoxazoloquinolines in high yields. Benzacridines, benzoquinolines and benzothioxanthenes having a trifluoromethyl group were highiy efficiently synthesized by the aromatic nucleophilic substitution reaction of 3 with bifunctional nucleophiles and the following intramolecular cyclizations.