Synthesis of 1,4-phenylene bridged bis-heterocyclic compounds

The synthesis of 1,4-phenylene bis-heterocyclic compounds is comprehensively reviewed.


Introduction
Heterocyclic chemistry comprises at least half of all organic chemistry research worldwide.][8][9][10][11][12] Therefore, it is not surprising that research on the synthesis of polyfunctionalized heterocyclic compounds has received significant attention.In recent years, attention has been increasingly paid to the synthesis of bis-heterocyclic compounds which exhibit various biological activities, [13][14][15][16][17][18][19][20] including antibacterial, fungicidal, tuberculostatic, antiamoebic, and plant growth regulative properties.The current first specialized review covers the synthesis of 1,4-phenylene-bisheterocyclic compounds from the late 1972 until 2011, and our survey of the literature on the synthesis of these heterocyclic has been divided according to the number of heteroatom in the heterocyclic.

1,4-Phenylene-bis-pyrroles
The 1,4-bis(1H-pyrrol-2-yl)benzene derivatives 18 were prepared by modification of the method of Engel and Steglich, 25 in accordance with the general pathway set out in Scheme 5.The acid chlorides 14 were reacted with allylamine 15 to give aryl bis(allylamides) 16.Subsequent treatment with phosgene furnished the aryl bis(allylimino chlorides) 17, which were used without isolation or purification in the following step.Compounds 17 were cyclized under basic conditions to form 18 (Scheme 5). 26,27

Scheme 50
The 1,4-bis(terpyridine)benzene 154 83 and 155 84 were synthesized by condensation of terephthalaldehyde 1 with a fourfold excess of 4-and/or 2-acetylpyridine in the presence of ammonium acetate in acetic acid (grinding method) 83 and/or under the action of a base in polyethylene glycol (PEG-300) 84 at 0 o C (Figure 19).

Figure 19
Shaker et al. 85 have been reported a synthetic route to 1,4-bis(4-pyridyl)benzenes 156 via the reaction of terephthalaldehyde ) with two equivalents of malononitrile and acetylhetarenes in the presence of ammonium acetate (Scheme 51).

Conclusions
Literature data published in the last 40 years have been summarized to help the reader to find information appropriate for the high synthetic potential of 1,4-phenylenebridged bis-heterocyclic compounds.Syntheses of many biologically active heterocyclic compounds belonging to this structural class have been reported.

Figure 25 Also
Figure 25

Figure 28 The
Figure 28