ChemInform Abstract: HALOGENATION OF ALKYL P‐TOLYL SULFONES WITH CARBON TETRAHALIDES. APPLICATION TO THE SYNTHESIS OF AROMATIC KETONES

Kotake, Hiroshi; Inomata, Katsuhiko; Kinoshita, Hideki; Sakamoto, Yohko; Kaneto, Yoko

doi:10.1002/chin.198103166

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“…Deprotonation of the acidic methanesulfonyl group with 1 equiv of n-BuLi resulted in a monoanion which was treated with an excess of carbon tetrachloride. 36 The resulting monochlorosulfonesbeing more acidic than the trichloromethyl anionswas deprotonated and chlorinated. This sequence was repeated until all the acidic hydrogen atoms were replaced by chlorine atoms.…”

Section: Chemistrymentioning

confidence: 99%

“…As the hydrochloride salt was difficult to crystallize, the oxalate salt of the amine was prepared. A saturated solution of anhydrous oxalic acid in dry Et2O was added to a methanolic solution of the amine 12, and the oxalate salt obtained was crystallized from MeOH-Et2O: mp 155-156 °C; EIMS m/z 164 (M + 1, 5), 163 (M + , 46), 162 (M + -1, 100), 134 (70), 132 (60), 130 (20), 117 (24), 105 (94), 91 (85), 77 (68), 51 (36), 44 (28). Anal.…”

Section: -Hydroxymethyl-1234-tetrahydroisoquinoline Oxalate (12)mentioning

confidence: 99%

“…The oil was purified by PCTLC (silica gel, 4 mm) using CH2Cl2/MeOH/NH4OH (250:20:1) as the eluent to give 18 as a viscous colorless liquid (0.117 g, 44 The hydrochloride salt was crystallized from MeOH-Et2O as a colorless solid: mp 225 °C dec (lit. 17 (38), 179 (57), 178 (46), 166 (10), 151 (100), 150 (36), 130 (38), 117 (20), 102 (27), 91 (69), 77 (75), 51 (49), 45 (45). Anal.…”

Section: -Hydroxymethyl-1234-tetrahydroisoquinoline Oxalate (12)mentioning

confidence: 99%

“…The hydrochloride salt was crystallized as a pale-yellow solid from MeOH-Et2O: mp 135-137 °C; IR (KBr) 3400, 1440, 1300 (SO2), 1150 (SO2), 1130, 1090, 880, 720, 680 cm -1 ; EIMS m/z 274 (M + 1, 10), 273 (M + , 33), 272 (M + -1, 100), 244 (21), 132 (M + -SO2Ph, 29), 131 (67), 130 (26), 125 (60), 103 (17), 91 (44), 77 (94), 65 (18), 51 (36) The hydrochloride salt was obtained as a yellow solid: mp 235 °C dec; EIMS m/z 190 (M + , 17), 189 (M + -1, 12), 161 (19), 148 (32), 120 (17), 119 (100), 118 (23), 91 (18), 57 (11). Anal.…”

Section: -Hydroxymethyl-1234-tetrahydroisoquinoline Oxalate (12)mentioning

confidence: 99%

“…7-Benzoyl-1,2,3,4-tetrahydroisoquinoline Hydrochloride (27‚HCl). The hydrolysis procedure as described 26 for the preparation of 7-acetyl-1,2,3,4-tetrahydroisoquinoline was performed on 45 (0.35 g, 1.0 mmol) to yield 27 (0.25 g, 86%) as a colorless solid: mp 244-246 °C dec; IR (KBr) 1640 (CO), 1600, 1580, 1270, 1250, 720 cm -1 ; 1 H NMR (DMSO-d6) δ 9.90 (bs, e, 2 H, NH2 + ), 7.75-7.55 (m, 7 H, ArH), 7.41 (d, 1 H, J ) 8.1 Hz, ArH), 4.34 (s, 2 H, H-1), 3.39-3.37 (m, 2 H, H-3), 3.14-3.12 (m, 2 H, H-4); 13 C NMR (DMSO-d6) δ 195.2 (CO), 137.3, 136.9, 135.2, 132.8, 129.6, 129.0, 128.6, 128.5, 128.2, 43.3 (C-1), 40.1 (C-3), 24.9 (C-4); EIMS m/z 238 (M + 1, 8), 237 (M + , 44), 236 (M + -1, 78), 208 (26), 132 (20), 131 (36), 015 (PhCO + , 34), 77 (100), 51 (30). Anal.…”

Section: -Hydroxymethyl-1234-tetrahydroisoquinoline Oxalate (12)mentioning

confidence: 99%

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Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

et al. 1998

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7-Substituted-1,2,3,4-tetrahydroisoquinolines (7-substituted-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), the enzyme involved in the biosynthesis of epinephrine. Unfortunately, most of these compounds also exhibit strong affinity for the alpha2-adrenoceptor. To design a selective (PNMT vs alpha2-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and alpha2-adrenoceptor affinity were investigated by evaluating a number of 7-substituted-THIQs. A classical quantitative structure-activity relationship (QSAR) study resulted in a three-parameter equation for PNMT (PNMT pKi = 0.599pi - 0.0725MR + 1. 55sigmam + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the alpha2-adrenoceptor (alpha2 pKi = 0.599pi - 0. 0542MR - 0.951sigmam + 6.45; n = 27, r = 0.917, s = 0.397). These equations indicated that steric effects and lipophilicity play a similar role at either active site but that electronic effects play opposite roles at either active site. Two binding orientations for the THIQs were postulated such that lipophilic and hydrophilic 7-substituents would not occupy the same region of space at either binding site. Using these two binding orientations, based on the lipophilicity of the 7-substituent, comparative molecular field analysis (CoMFA) models were developed that showed that the steric and electrostatic interactions at both sites were similar to those previously elaborated in the QSAR analyses. Both the QSAR and the CoMFA analyses showed that the steric interactions are similar at the PNMT active site and at the alpha2-adrenoceptor and that the electrostatic interactions were different at the two sites. This difference in electrostatic interactions might be responsible for the selectivity of THIQs bearing a nonlipophilic electron-withdrawing group at the 7-position. These QSAR and CoMFA results will be useful in the design of potent and selective (PNMT vs alpha2-adrenoceptor affinity) inhibitors of PNMT.

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Section: Chemistrymentioning

confidence: 99%

Section: -Hydroxymethyl-1234-tetrahydroisoquinoline Oxalate (12)mentioning

confidence: 99%

Section: -Hydroxymethyl-1234-tetrahydroisoquinoline Oxalate (12)mentioning

confidence: 99%

Section: -Hydroxymethyl-1234-tetrahydroisoquinoline Oxalate (12)mentioning

confidence: 99%

Section: -Hydroxymethyl-1234-tetrahydroisoquinoline Oxalate (12)mentioning

confidence: 99%

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Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

et al. 1998

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ChemInform Abstract: HALOGENATION OF ALKYL P‐TOLYL SULFONES WITH CARBON TETRAHALIDES. APPLICATION TO THE SYNTHESIS OF AROMATIC KETONES

Abstract: Die Alkyltolylsulfone (I), (III) und (V) werden über die entsprechenden Carbanionen mit CCl4 in die Halogenide (II), (IV) bzw. (VI) übergeführt, wobei die Ergebnisse im Widerspruch zu früheren Literaturangaben stehen.

Cited by 1 publication

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Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

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ChemInform Abstract: HALOGENATION OF ALKYL P‐TOLYL SULFONES WITH CARBON TETRAHALIDES. APPLICATION TO THE SYNTHESIS OF AROMATIC KETONES

Abstract: Die Alkyltolylsulfone (I), (III) und (V) werden über die entsprechenden Carbanionen mit CCl4 in die Halogenide (II), (IV) bzw. (VI) übergeführt, wobei die Ergebnisse im Widerspruch zu früheren Literaturangaben stehen.

Cited by 1 publication

References 1 publication

Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α2-Adrenoceptor,1

Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α2-Adrenoceptor,1

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Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1