1,10-Phenanthroline synthesis 3-methyl

The first synthesis of a derivative of 2,8-phenanthroline was reported by Merz, Weidlich, and Fink13 in 1964. They prepared 5,6-dimethoxy-2,8-phenanthroline (34) (isolated as the dipicrate) in very low yield by conducting a double Pomeranz-Fritsch isoquinoline synthesis on 4,5-dimethoxyisophthalaldehyde. The parent compound was prepared 2 years later12 in 25-35% yield, along with 1,9-phenanthroline (4%), by the photocyclization of trans-1 (3-pyridyl)-2-(4-pyridyl)ethylene in benzene. This reaction was used by Hiinig and his colleagues15 to prepare an N,N -dimethyl diquaternary salt of 2,8-phenanthroline by methylating the crude product from the irradiation reaction. 

Phenanthroline was first claimed to have been synthesized by a double Pomeranz-Fritsch isoquinoline synthesis.11 It has recently been prepared12 in about 12% yield by the irradiation of trans-l,2-di(3-pyridyl)ethylene in benzene, along with 1,8-phenanthroline (12-20%) and 1,10-phenanthroline (1-2%). The melting point is quite different from that recorded earlier by Ruggli and Schetty.11 This latter method has subsequently been used15 to prepare an AT, AT -dimethyl diquaternary salt of 3,8-phenanthroline by methylating the crude product from the irradiation reaction. 

The first phenanthroline to be prepared was 1,7-phenanthroline by Skraup and Vortmann in 1882, followed one year later by the synthesis of 4,7-phenanthroline. 2-Methyl-1,10-phenanthroline was the first 1,10-phenanthroline to be reported, the parent compound being synthesized 9 years later by Blau. 1,8-Phenanthroline was prepared in 1945. The synthesis of the 3,8-isomer was claimed in 1940, but there is doubt about the structure of the product. The remaining isomers, 1,9-, 2,7-, 2,8-, 2,9-, 3,7-, and authentic 3,8-phenanthroline, were not obtained until 1966, when Perkampus and Kassebeer formed all the phenanthrolines by irradiation of appropriate l,2-di(pyridyl)ethylenes. A derivative of 2,8-phenanthroline had, however, been synthesized 2 years earlier. ... 

The first phenanthroline to be prepared was 1,7-phenanthroline by Skraup and Vortmann6 in 1882, followed one year later by the synthesis of 4,7-phenanthroline.7 2-Methyl-1,10-phenanthroline was the first 1,10-phenanthroline to be reported,8 the parent compound being synthesized... 

Improvements in the double Skraup synthesis of 1,7-phenanthroline from m-phenylenediamine now enable a yield of 70% to be achieved.163 The Skraup reaction continues to be used for the synthesis of 1,7-phen-anthrolines starting from the substituted 5-aminoquinolines. S-Chloro-6-hydroxy-1,7-phenanthroline (18) has been prepared in this way,164 and an improved synthesis of 6-hydroxy-1,7-phenanthroline was reported.165 As expected, the Skraup reaction on 5-aminoquinaldine affords 8-methyl-1,7-phenanthroline,166 not 2-methyl-1,7-phenanthroline as it was previously named.8 The extension of the Skraup reaction using methyl vinyl ketone instead of glycerol has been applied to 5-aminoquinoline to afford 4-methyl-1,7-phenanthroline.166 A related condensation using 2-hydroxymethylenecyclohexanone provides a route to benzo-substituted 1,7-phenanthrolines.167 7-Aminoquinoline with mesityl oxide in the presence of iodine gives 8,8,10-trimethyl-7,8-dihydro-l,7-phenanthroline (19).168... 

Applications of the Conrad-Limpach reaction to the synthesis of 1-hydroxy-4,7-phenanthrolines or, more correctly, l-oxo-l,4-dihydro-4,7-phenanthrolines, from p-phenylenediamine or 6-aminoquinolines continue to be reported. l,10-Dihydroxy-3,8-dimethyl-4,7-phenanthroline has again been prepared from p-phenylenediamine,234 hot diphenyl ether being used to effect the cyclization. Other examples include the new or improved preparations of l-hydroxy-3-methyl-, 10-amino-l-hydroxy-3-methyl-,232 2-(y-chlorocrotonyl)- l,10-dihydroxy-3,8-dimethyl-, and 2,9-bis (y- chlorocrotonyl)-1,10- dihydroxy - 3,8 - dimethyl - 4,7 - phenanthro-lines.235 Compounds prepared in this way have been patented as antiasthmatic agents.178 A closely related synthesis employing poly-phosphoric acid as cyclizing agent has yielded l-hydroxy-3-phenyl-4,7-phenanthroline.236... 

Further examples of the Knorr reaction for the synthesis of 3-hydroxy-4,7-phenanthrolines are reported. A modification of the original synthesis239 of 3-hydroxy-1-methyl-4,7-phenanthroline involves isolation of the intermediate acetoacetanilide followed by ring closure with sulfuric acid.232 10-Amino-3-hydroxy-l-methyl-4,7-phenanthroline was obtained similarly from 4-amino-6-acetoacetamidoquinoline. Several 2-substituted l,3-dihydroxy-4,7-phenanthrolines were obtained likewise from diethyl alkylmalonates.101... 

The synthesis of 2-methyl-1, 10-phenanthroline starting from 8-amino-2-methylquinoline was achieved by Heindel and Ohnmacht383 by a seven-stage sequence, using DM AD. 

ET-initiated alkylation of azines in the presence of alkyl halides has been found to occur under electrochemical conditions according to Scheme 43. Either alkylated dihydroheterocycles or the rearomatized products are obtained. As an example, electroreduction of quinoline in the presence of 1-bromoadamantane gives alkylated quinolines (10 % in position 2, 5 % in position 7) and 2-methyl- and 2-methoxyquinoline give the 7-adamantyl derivative in 20 and 23 % yield, respectively. 1,10-Phenanthroline gives bis(adamantyl) derivatives, whereas isoquinoline and phenanthridine give the 6-adamantyl-5,6-dihydro and the 9-adamantyl-9,10-dihydro derivatives, respectively [132]. Reaction with terr-butyl chloride also gives alkylated dihydroheterocycles [133]. Arylation has also been performed, e.g. in the synthesis of pyrazolophenanthridines (62, Scheme 44) [134]. 

Several examples have been reported of the preparation of 4,7-phenanthrolines from substituted 6-aminoquinolines by the Skraup and related reactions. In this way, 5-methoxy-, 5-chloro-, 3-methyl-6-methoxy-, l-methyl-, and l,2,3,4-tetrahydro-4-methyl-4,7-phenanthrolines have been synthesized while improvements have been made to the synthesis of the 3-methyl derivative. The Skraup reaction has also been applied to quaternary salts of 6-aminoquinolines. For example, 5-chloro-4-methyl-4,7-phenanthrolinium iodide (36) was obtained from the methiodide of 6-acetamido-8-chloroquinoline (35). Cyclizations starting from aminocarbostyrils have also been reported. Thus, 6-amino-1-methylcarbostyril (37) was condensed with paraldehyde in the presence of concentrated hydrochloric acid to afford 3,4-dihydro-4,8-dimethyl-3-oxo-4,7-phenanthroline (38), while under Skraup conditions, with glycerol as condensing agent, 6-amino-4-methylcarbostyril afforded 3,4-dihydro- l-methyl-3-oxo-4,7-phen-... 

Template synthesis 2,6-diacetylpyridine + 2,9-di(l-methyl-hydrazino)- , 10-phenanthroline + Ni(BF4)2 hydrate in H2O... 

Leventis, N, Rawashdeh, A-M M, Elder, I A, Yang, J, Dass, A, Sotiriou-Leventis, C (2004) Synthesis and Characterization of Ru(II) Tris( 1,10-phenanthroline)-Electron Acceptor Dyads Incorporating the 4-benzoyl-N-methylpyridinium cation or N-Benzyl-N -methyl-viologen Improving the Dynamic Range, Sensitivity and Response Time of Sol-Gel Based Optical Oxygen Sensors. Chem Mater 16 1493-1506. 

Leventis N, Rawashdeh A-M M, Elder 1 A, Yang J, Dass A, Sotiriou-Leventis C (2004) Synthesis and characterization of Ru(ll) tris(l,10-phenanthroline)-electron acceptor dyads incorporating the 4-benzoyl-Af-methylpyridinium cation or JV-benzyl-/V -methyl viologen. Improving the dynamic range, sensitivity, and response time of sol-gel-based optical oxygen sensors. Chem Mater 16 1493-1506. 

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