416. Synthesis and reactions of some cyclohexadienones

Merchant, J. R.; Desai, V. B.

doi:10.1039/jr9640002258

Cited by 4 publications

(10 citation statements)

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“…4-Chloro-2-ethylbenzoic acid (18) was thus obtained using 2.3 equiv of LDA at -70°C. 13 The 4-bromo-2-ethylbenzoic acid (19) could be prepared from 17 employing the same protocol.…”

Section: Chemistrymentioning

confidence: 99%

“…b Analyses for C, H, Cl, and S are within ±0.4% of the expected value for the formula. c The starting material was 4-chloro-2,3-dimethylbenzoic acid 3 Physical Constants for 5-(Methylsulfonyl)benzoic Acid Methyl Esters 48 − 60 compdR 2 R 3 R 4 methodreaction temperature, a °Coverall yield, %mp, °Crecryst solventformula b 48 Me H Cl E 140 39 152−153 MeOH C 10 H 11 ClO 4 S 49 Me H F E 125 54 137−139 i -PrOH C 10 H 11 FO 4 S·0.25H 2 O 50 Me Cl Cl E 140 69 124−125 Et 2 O C 10 H 10 Cl 2 O 4 S 51 H H F E 140 24 108 i -PrOH C 9 H 9 FO 4 S 52 Et H Br E 120−130 45 102−104 ( i -Pr) 2 O C 11 H 13 BrO 4 S 53 Me H Br E 140 55 146−148 EtOAc C 10 H 11 BrO 4 S 54 Et H Cl E 140 59 98−100 i -PrOH C 11 H 13 ClO 4 S 55 F H F E 155 11 140 EtOAc C 9 H 8 F 2 O 4 S 56 Me Me Cl F 82 137 EtOAc C 11 H 13 ClO 4 S 57 Me H Me E 140 31 141−142 MeOH C 11 H 14 O 4 S 58 Cl H Cl E 140 43 154−155 EtOH C 9 H 8 Cl 2 O 4 S 59 c Me Me Me <...

…”

Section: Chemistrymentioning

confidence: 99%

“…b Analyses for C, H, Cl, and S are within ±0.4% of the expected value for the formula. c The starting material was 4-chloro-2,3-dimethylbenzoic acid …”

Section: Chemistrymentioning

confidence: 99%

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(2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na⁺/H⁺ Antiporter Inhibitors

1997

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The inhibition of the Na+/H+ exchanger during cardiac ischemia and reperfusion has been shown to be beneficial for the preservation of the cellular integrity and functional performance. The aim of the present investigation was to come up with potent and selective benzoylguanidines as NHE inhibitors for their use as an adjunctive therapy in the treatment of acute myocardial infarction. During the course of our investigations it became clear that the substitution ortho to the acylguanidine was of crucial importance for the potency of the compounds. 4-Chloro- and 4-fluoro-2-methylbenzoic acids 6 and 7 were prepared using the directed ortho metalation technique with the carboxylic acid as the directing group. With the LDA/methyl iodide system the 2-methyl group could be extended to an ethyl group. 4-Alkyl groups were inserted by the palladium-catalyzed cross-coupling reaction into the 4-bromo-2-methylbenzoic acid methyl ester (20). Starting with benzoic acids 6-19, the methylsulfonyl group was introduced by a sequence of standard reactions (sulfochlorination, reduction, and methylation). 4-Aryl derivatives 68-75 were synthesized by the palladium-catalyzed Suzuki reaction. A large number of nucleophilic displacement reactions in the 4-position were carried out with S-, O-, and N-nucleophiles as well as with the cyano and trifluoromethyl group. Using the ester method, acid chlorides, or Mukaiyama's procedure, the 5-(methylsulfonyl)benzoic acid derivatives were finally converted to the (5-(methylsulfonyl)benzoyl)guanidines 165-267 with excessive guanidine. In some cases nucleophilic substitutions with pyridinols and piperidine derivatives were carried out at the end of the reaction sequence with the 4-halo-N-(diaminomethylene)-5-(methylsulfonyl)-benzamides. Variations in the 4-position were most reasonable, but the volume of the substituents was of crucial importance. Substitution in the 3- and particularly in the 6-position led to considerable worsening of the inhibitory effects of the Na+/H+ exchanger. The 2-methyl compounds, however, showed without exception higher in vitro activities than their respective demethyl counterparts as they are exemplified by the reference compounds 266 and 267, obviously caused by a conformational restriction of the acylguanidine chain. The development compound (2-methyl-5-(methylsulfonyl)-4-pyrrolobenzoyl)guanidine, methanesulfonate (246) is a NHE-1 subtype specific NHE inhibitor, being 27-fold more potent toward the NHE-1 than the NHE-2 isoform. 246 was found to act cardioprotectively not only when given before an experimentally induced ischemia, but also curatively after the onset of symptoms of acute myocardial infarction when given prior to the induction of reperfusion.

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“…4-Chloro-2-ethylbenzoic acid (18) was thus obtained using 2.3 equiv of LDA at -70°C. 13 The 4-bromo-2-ethylbenzoic acid (19) could be prepared from 17 employing the same protocol.…”

Section: Chemistrymentioning

confidence: 99%

…”

Section: Chemistrymentioning

confidence: 99%

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(2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na⁺/H⁺ Antiporter Inhibitors

1997

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“…1 : mp 146−147 °C (CH 2 Cl 2 / n -C 6 H 14 ) (lit . mp 146−147 °C); 1 H NMR (200 MHz, CDCl 3 ) δ 1.70 (d, 3H, J = 1.2 Hz), 6.46 (d, 2H, J = 8.8 Hz), 7.26 (d, 2H, J = 8.8 Hz); 13 C NMR (50 MHz, CDCl 3 ) δ 24.8 (q), 49.8 (s), 55.9 (s), 130.7 (d, 2C), 148.2 (d, 2C), 184.5 (s); IR (KBr) 1658 cm -1 ; HRMS m / z calcd for C 8 H 7 OBr 3 355.8046, found 355.8010, calcd for C 8 H 7 OBr 2 81 Br 357.8026, found 357.8031, calcd for C 8 H 7 OBr 81 Br 2 359.8006, found 359.8026, calcd for C 8 H 7 O 81 Br 3 361.7986, found 361.8008.…”

Section: Methodsmentioning

confidence: 99%

“…4 : mp 117−118 °C ( n -C 6 H 14 ) (lit . mp 116−117 °C); 1 H NMR (200 MHz, CDCl 3 ) δ 1.68 (s, 3H), 1.98 (d, 3H, J = 1.4 Hz), 6.45 (d, 2H, J = 10.2 Hz), 7.00−7.03 (m, 1H), 7.22 (dd, 1H, J = 10.2, 3.4 Hz); 13 C NMR (50 MHz, CDCl 3 ) δ 16.3 (q), 24.7 (q), 51.2 (s), 55.9 (s), 130.6 (d), 137.6 (s), 143.4 (d), 147.9 (d), 185.2 (s); IR (KBr) 1662, 1638 cm -1 ; HRMS m / z calcd for C 9 H 9 OBr 3 369.8202, found 369.8230, calcd for C 9 H 9 OBr 2 81 Br 371.8182, found 371.8171, calcd for C 9 H 9 OBr 81 Br 2 373.8162, found 373.8148, calcd for C 9 H 9 O 81 Br 3 375.8142, found 375.8117.…”

Section: Methodsmentioning

confidence: 99%

Photoreactions of 4-(Tribromomethyl)-4-methyl-2,5-cyclohexadienone and Its Derivatives with Amines: Radical Cyclization and Ring Expansion Reactions Promoted through Photoinduced Electron Transfer Processes

et al. 1999

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Photoreactions of 4-(tribromomethyl)-4-methyl-2,5-cyclohexadienone (1) and its derivatives with amines were studied. Irradiation of 1 with amine produced 4-bromo-5-methyltropone (2) along with 4-(dibromomethyl)-4-methyl-2,5-cyclohexadienone (3). The effects of solvent, added water, and the structural variation in amine on the product ratio were explored. Isolation of the amine-derived products revealed that oxidative dealkylation of amine proceeded during the photoreaction. On the basis of the results obtained, a reaction mechanism involving fragmentation of the dienone anion-radical and amine cation-radical pair is proposed. Photoreactions of dienone 4 with amine produced the tropones 6 and 7, whereas tropone 9 was produced from 8. Trialkyltin radical-induced reductions of dienones 1 and 4 with tri-n-butyltin hydride demonstrated common features with the photoreactions. It was also found that irradiation of dienone 3 with amine produced 4-methyltropone (10).

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Z incke‐ S uhl Reaction

2007

Hawley's Condensed Chemical Dictionary

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416. Synthesis and reactions of some cyclohexadienones

Cited by 4 publications

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(2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na⁺/H⁺ Antiporter Inhibitors

(2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na⁺/H⁺ Antiporter Inhibitors

Photoreactions of 4-(Tribromomethyl)-4-methyl-2,5-cyclohexadienone and Its Derivatives with Amines: Radical Cyclization and Ring Expansion Reactions Promoted through Photoinduced Electron Transfer Processes

Z incke‐ S uhl Reaction

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416. Synthesis and reactions of some cyclohexadienones

Cited by 4 publications

References 0 publications

(2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na+/H+ Antiporter Inhibitors

(2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na+/H+ Antiporter Inhibitors

Photoreactions of 4-(Tribromomethyl)-4-methyl-2,5-cyclohexadienone and Its Derivatives with Amines: Radical Cyclization and Ring Expansion Reactions Promoted through Photoinduced Electron Transfer Processes

Z incke‐ S uhl Reaction

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About

(2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na⁺/H⁺ Antiporter Inhibitors

(2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na⁺/H⁺ Antiporter Inhibitors