Synthesis and Characterization of Novel Functionally Substituted Planar Pyrimidothienoisoquinolines and Nonplanar (3aR, 4S, 9aS)-pyrazolo[3,4-g]isoquinolines

Abstract

6,7,-thiones 2a,b are prepared and dehydrated to give 7-acetyl-8-aryl-4-cyano-1,6-dimethyl-6hydroxy-7,8-dihydrodroisoquinolin-3(2H)-thiones 6a,b via a novel method by heating with acetyl chloride in acetic acid. The reaction of both compounds 2a,b and 6a,b with N-aryl-2chloroacetamides 7a−c under two different conditions gave the same corresponding products, 7acetyl-8-aryl-3-(N-aryl)carbamoylmethylsulfanyl-4-cyano-1,6-dimethyl-7,8-dihydroisoquinolines 8a−e, in high yields. On treatment of compounds 8a,b,e in methanol with a slightly excess molar amount of sodium methoxide, they underwent intramolecular Thorpe−Ziegler cyclization followed by spontaneous aromatization, providing the planar 7-acetyl-1-amino-6-aryl-2-(Naryl)carbamoyl-5,8-dimethyl-8,9-dihydrothieno[2,3-c] isoquinolines 9a,b,e in good yield. Cyclocondensation reactions of 6a,b with phenyl hydrazine, thiosemicarbazide, or hydrazine hydrate led to the formation of nonplanar (3aR, 4S, 9aS)-pyrazolo[3,4-g]isoquinolines 11a, 11b, and 13, respectively. The reaction of compound 13 with 2-chloromethylquinazolin-4(3H)-one in the presence of anhydrous sodium acetate gave the expected thienopyrazoloisoquinolone 14. Heating the latter compound ( 14) with triethyl orthoformate in glacial acetic acid afforded the fused heptacyclic compound 15. All of the synthesized compounds were characterized based on their full spectral analyses such as IR, 1 H nuclear magnetic resonance (NMR), and mass spectrometry (MS). Moreover, the crystal structure of compound 6a was elucidated by X-ray diffraction analysis.

Synthesis, characterization and crystal structure of some novel partially hydrogenated isoquinolines and their fused heterocyclic systems

“…We have obtained the tetrahydropyrazoloisoquinoline 13 in its crystalline form that was subjected to X-ray diffraction analysis. The crystal structure indicates that the pyrazole ring takes the tetrahedral angle with the plane of isoquinoline moiety as predicted before in our previous work [26]. In a similar manner, the crystal structure tetrahydroisooxazolo-isoquinoline 14 may possess the same as that of 13; that is, the isooxazole ring takes the tetrahedral angle with the plane of isoquinoline moiety.…”

“…An attempt to synthesize compound 2 by heating compound 3 , which was previously synthesized by reacting of 1 with acetyl chloride in acetic acid [26], with aqueous solution of potassium hydroxide has succeeded. Herein, the conversion of 3 into 2 by the aforementioned method supports the second mechanism for compound 2 (Scheme 4).…”

“…Cyclocondensation of 3 with both hydrazine hydrate and/or hydroxylamine hydrochloride afforded tetrahydropyrazoloisoquinoline 13 [26] and tetrahydroisoxazoloisoquinoline 14 , respectively (Scheme 7).…”

Crystal structure and Hirshfeld surface analysis of 2-{[7-acetyl-4-cyano-6-hydroxy-8-(4-methoxyphenyl)-1,6-dimethyl-5,6,7,8-tetrahydroisoquinolin-3-yl]sulfanyl}acetic acid ethyl ester

“…Other tetrahydroisoquinolines were used as inhibitors including B-raf V600E or p38 kinase inhibitors (Lu et al, 2016;Rosales et al, 2007). The THISQ core can easily be functionalized to build other heterocyclic rings on the carbocyclic ring (Xu et al, 2002;Carroll et al, 2007;Demers et al, 2008, Marae et al, 2021a. Recently, we have used some compounds related to THISQ as durable fluorescent dyes for cotton (Marae et al, 2021b).…”

Pyridine Derivatives as Insecticides. Part 3. Synthesis, Crystal Structure, and Toxicological Evaluation of Some New Partially Hydrogenated Isoquinolines against Aphis gossypii (Glover, 1887)

“…Synthetic Procedures for 7-Ethylsulfanyl-4-phenyl-1-thiocarbamoyl-3,5,9a-trimethyl-3a,4,9,9a-tetrahydro-1H-pyrazolo [3,4- Method B. To a mixture of 7 27 (2.04 g, 5 mmol) and ethyl iodide (0.4 mL, 5 mmol) in ethanol (50 mL), sodium acetate trihydrate (0.75 g, 7 mmol) was added. The reaction mixture was refluxed for 2 h and then allowed to cool.…”