Pyrazolo isoindoles

The nitration of the reduced l//-pyrazolo[5,l-n]isoindole (54) gives the 2,4-dinitrophenyl derivative, without attack at the benzo ring (47JCS829 48JCS1249). 

The pyrazolo[l,2-a]pyridazine (55) reacts with sodium methoxide in boiling methanol, presumably via preliminary deprotonation at benzylic carbon. After 8 h a mixture of (56 72%) and the Hofmann-type elimination product (57 12%) is obtained, but after 25 h only (57 75%) is isolated. The imino bond u 1640 cm ) of (57) may be saturated with sodium borohydride. With potassium t-butoxide in t-butyl alcohol at reflux, the rearranged isoindole (58) is obtained (Scheme 22) (74CPB2142). Scheme 23 shows a rearrangement similar to (55) (56) for which a radical mechanism has been suggested. However, here,... 

Several derivatives of 4//-pyrazolo[l,5-a]indole (597) and 8/f-pyrazolo[5,l-a]isoindole (598) have been found to have contraceptive activity <84EJM215, 82EJM223, 84GEP(0)3314843), and some of the l//-pyrazolo[l,2-a]indazol-4-ium derivatives (599) have been found to act as bronchodilators <82EUP55450). 

A stirred refluxing ethanolic soln. of 3-(4-methoxyphenacyI)phthalide treated consecutively with an aq. soln. of 2 moles hydrazine dihydrochloride and 4 moles triethylamine, and heating continued 2-3 hrs. -> 2-(4-methoxyphenyl)-3,3a-di-hydro-8H-pyrazolo[5,l-a]isoindol-8-one (Y 88.5%) stirred and refluxed 5 hrs. with 2,3-dichloro-5,6-dicyanobenzoquinone, added in 2 portions, in benzene 2-(4-methoxyphenyl)-8H-pyrazolo[5,l-a]isoindol-8-one (Y 83%). F. e. s. E. W. Bous-quet et al., J. Org. Chem. 40, 2208 (1975). 

Methyl-2,3,5,10-tetrahydro-lH-pyrazolo[l,2-b]phthalazinium iodide added to a soln. of K in rt-butanol, and refluxed 3 hrs. under N2 2-(3-methylamino-propyl)isoindole. Y 84%. F. e. s. A. Nakamura and S. Kamiya, Chem. Pharm. Bull. 22, 2142 (1974). 

DPX 1840 3,3a-dihydro-2-(p-methoxyphenyl)-8H-pyrazolo-(S,l-a]-isoindol-8-one, a synthetic growth regulator affecting auxin transport, ethylene production and root growth, etc. in cotton and soybeansi... 

Specificity of the Auxin Transport System. Comparative studies with chemically closely related compounds reveal a positive correlation between auxin activity and degree of basipetal polarity in the transport of these substances (e.g.. Went and White 1939, Leopold and Lam 1961, Jacobs 1967, Hertel etal. 1969, Veen 1972). Further, the basipetal transport of auxins is specifically inhibited by substances such as TIBA, naphthylphthalamic acid (NPA), 3,3a-dihydro-2-(p-methoxyphenyl)-8H-pyrazolo[5,la] isoindol-8-one (DPX 1840) (see Sect. 3.3.4.3) not only in treated sections but also when they are applied to intact plants at the loci of natural auxin production (see p 100). In summary, the numerous transport studies make certain the presence of a unique transport system, which is specific for auxin molecules, and which moves the hormone basipetally from the natural auxin sources in the shoot and then on to the root to regulate growth and other developmental processes. It is clear that this system is fully functional in tissue sections which is the material which has been used most in transport studies. 

Cl5H13NO, 6,7-Dihydro-6-methyl-5H-dibenz[c,e]azepin-5-one, 39B, 211 Cl 5H1 i,Ni,02 f 4,5-Benzo-8,11,11 - trimethyl-1, 2,7,1 0-tetraazatricyclo-[7.3,0.0 ]dodeca-2,9-diene-6,12-dione, 46B, 273 Cl5H1sBr2N, 1,1-Bis(bromoethyl)-l,2,3,4-tetrahydroacridine, 46B, 273 Cl5H15N2O5, Methyl 8-methoxycarbonylmethyl-2-oxo-2,3,3a,8-tetrahyd-ro-1H-pyrazolo[5,1-a]isoindol-3-carboxylate, 41B, 346 Cl5H16N2O2, 5,7-Dihydroxy-6,6-dimethyl 6,7-dihydrodibenzo[d,f](1,3)-diazepine, 44B, 256... 

Intramolecular Direct Arylation of Heterocycles. Pivalic acid can promote a Pd-catalyzed intramolecular C-H activation process to furnish interesting pyrazolo[5,l-a]isoindoles (eq 22). ... 

Both LiCl and pivalic acid were required to maximize product yield and to suppress the formation of the heterodimer, albeit excess LiCl retarded the reaction. Other additives, such as Ag2C03 and AgOAc, were inferior however, AcOH was comparable to PivOH (67% vs. 75%). The chloro analog could be cyclized without LiCl in good yield (55%). A wide range of pyrazolo[5,l-a]isoindoles was accessible. Electron-deficient and electron-rich aryl bromides were compatible. Steric hindrance did not negatively impede the reaction. Other heteroarenes, such as naphthyl, thienyl, and pyridyl moieties, were viable substrates, albeit afforded lower yields of the product (50-55%). In addition, 2-bromo-phenethyl-pyrazole could be cyclized to generate 5,6-dihydropyrazolo[5,l-a]isoquinoline (eq 23). 

The resulting pyrazolo[5,l-a]isoindole could be further functionalized via intermolecular direct arylation (eq 24). 

Scheme 7.17 One-pot synthesis of pyrazolo[5,l-a]isoindoles from l-(2-bromophenyl) buta-2,3-dien-l-one, hydrazine hydrate, and isocyanide...

Tian M, He Y, Zhang X, Fan X (2015) Synthesis of Pyrazolo[5,l-a]isoindoles and Pyrazolo [5,l-a]isoindole-3-carboxamides through one-pot cascade reactions of l-(2-Bromophenyl) buta-2,3-dien-l-ones with isocyanide and hydrazine or acetohydrazide. J Org Chem 80 (15) 7447-7455... 

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