The reaction of an aromatic heterocycle with a proton is called a protonation. One of articles about this theory is 《New derivatives of 1,4-disubstituted piperazine》. Authors are Morren, H. G.; Denayer, R.; Linz, R.; Mathieu, J.; Strubbe, H.; Trolin, S..The article about the compound:1-(Bis(4-chlorophenyl)methyl)piperazinecas:27469-61-0,SMILESS:ClC1=CC=C(C=C1)C(N2CCNCC2)C3=CC=C(Cl)C=C3).COA of Formula: C17H18Cl2N2. Through the article, more information about this compound (cas:27469-61-0) is conveyed.
New 1,4-disubstituted piperazines were prepared and their tranquillizing properties and action on gastric ulcers examined ο-(Chlorobenzhydryl)piperazine with Me3N and PhCH2Cl in PhMe gave N-(ο-chlorobenzhydryl)-N’-benzylpiperazine, b0.005 210°; di-HCl salt, m. 223°. By refluxing 2 moles chloroethoxyethanol or chloroethoxyethoxyethanol with 110 g. Me3N and 1 mole of various substituted benzhydrylpiperazines the following N-(R1-substituted-benzhydryl)-N’-(R-substituted) piperazines were prepared (R’ = CH2CH2OCH2CH2OH) (R and b.p./mm. given): ο-Cl, 215°/0.01; p-Br, 224°/0.01; m-Cl, 215°/0.5; m-Br, 225°/0.02; ο-Br, 215-20°/0.1; m-OMe, 225°/ 0.07; m-Me, 210°/0.1; ο-C5H11O, 248°/0.01; m-Bu, 215°/0.01; ο-Me, 205°/0.01. (R = CH2CH2OCH2CH2OCH2CH2OH): m-Br, 240-5°/0.01; ο-Br, 240-5°/0.005; p-Br, 245-50°/0.02; ο-Cl, 240-5°/0.01. In an N atm. 0.1 g. atom Na is dissolved with warming in a convenient alc., after cooling 1-benzhydryl-4-(ω-chloroalkanoyl)piperazine in toluene added, the toluene distilled, the mixture heated 3 hrs at 140°, to the cooled liquid 3:7 EtOH-C6H6 added, the filtrate evaporated, and the residue distilled in vacuo. By this method the following N-(ο-chlorobenzhydryl)-N’-(R-substituted) piperazines were prepared (R and b.p./mm. given): CH2CH2O(CH2)5OH, 225°/0.003; CH2CH2OCH2CH(OH)CH2OH, 200°/0.05; CH2CH2OCH.(CH2)2.CH(OH). CH2.CH2, 260°/0.05. By refluxing 0.1 mole 1-(ο-chlorobenzhydryloxyethyl)piperazine with 0.11 mole triethylamine and 0.1 mole halogenated derivative, RX, in xylene 12 hrs. the following N-(ο-chlorobenzhydryloxyethyl)-N’-(R-substituted)piperazines were prepared (R and b.p./mm. given): Bu, 210°/0.1; (CH2)2OCH2CH2OH, 250°/0.03 (in the presence of excess chloroethoxyethanol); CH2Ph, 230-5°/0.1; ο-MeC6H4CH2, 234-6°/0.01; ο-ClC6H4CH2, 240°/0.1; ο-ClC6H4CO, 255°/0.1; p-Me3CC6H4CH2O(CH2)2, 245-50°/0.1. By refluxing 0.1 mole monosubstituted piperazine with 0.11 mole triethylamine and 0.1 mole of various appropriate ω-chloroalkanoyl and benzhydryl oxides in xylene during 12 hrs. the following N-[(R’-substituted)benzhydryloxyalkylene] – N’ – (R-substituted)piperazines (alkylene = (CH2)n) were prepared (R1, R, n, and b.p./mm. given): ο-Cl, H(I), 2, 193-5°/0.15; ο-Cl, Me, 2, 185-190°/0.1; ο-Cl, CHMe2, 2, 184-6°/0.04; ο-Me, CHMe2, 2, 170°/0.005; ο-Cl, CH2CHMe2, 2, 185-190°/0.02; ο-Cl, (cyclohexyl, 2, 235-40°/0.05; ο-Cl, 3-methylcyclohexyl, 2; 230-2°/0.01; H, CH2CH2OH, 2, 220°/0.1; ο-Cl, CH2CH(OH)CH2OH, 2, – (decompose); ο-Cl, ο-Me-C6H4CH2; 2; 235°/0.05; ο-Me, m-MeC6H4CH2, 2, 224°/0.015; m-Cl, m-MeC6H4CH2, 2, 250°/0.1; ο-Me, ο-MeC6H4CH2, 2, 215°/0.005; ο-Cl, CHMe2, 3, 215°/0.7; ο-Cl, m-MeC6H4CH2, 3, 250°/0.5; ο-Cl, ο-MeC6H4CH2, 3, 260°/0.1; ο-Cl, CHMe2, 4, 210°/0.1; ο-Cl, m-MeC6H4CH2, 4, 245°/0.1; ο-Cl, CHMe2, 6, 230°/0.2; ο-Cl, ο-MeC6H4CH2, 6, 265°/0.1. N-[2-(ο-Chlorobenzhydryloxy)ethyl]-N’-(2-hydroxyethyl)piperazine (II), b0.1 230°, was prepared in 65% yield by melting at 150° 1.1 mole N-hydroxy-N’-ethylpiperazine, adding dropwise 0.5 mole ο-ClC6H4CHClPh, and warming 2 hrs. at 150°. The mixture is cooled at 75° and 250 ml. C6H6 added. After cooling and addition of NaOH the benzene layer is washed, evaporated, and the residue distilled in vacuo. II (0.1 mole) and 0.11 mole NaNH2 in 100 ml. toluene is refluxed until no NH3 is liberated. After cooling at 30° 0.12 mole p-tert-butylbenzyl bromide is added and the mixture refluxed 2 hrs. The cooled mass is extracted with dilute HCl, the acid-extract basified with K2CO3, and extracted with C6H6. After evaporation the residue is distilled in vacuo, giving 45% N-[2-(ο-chlorobenzhydryloxy)ethyl] – N’- [2-(p-tert-butylbenzyloxy)ethyl]piperazine, b0.1 275°. By refluxing 0.1 mole I, 11 g. triethylamine, 100 ml. toluene, and 0.1 mole AcCl during 2 hrs. N-[2-(ο-chlorobenzhydryloxy)ethyl]-N’-acetylpiperazine (III) is formed, b0.02 220-5°. Reduction of III with LiAlH4 yielded 88% N-[2-(ο-chlorobenzhydryloxy)ethyl]-N’-ethylpiperazine, b0.03 178-80°.
This literature about this compound(27469-61-0)COA of Formula: C17H18Cl2N2has given us a lot of inspiration, and I hope that the research on this compound(1-(Bis(4-chlorophenyl)methyl)piperazine) can be further advanced. Maybe we can get more compounds in a similar way.
Reference:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics