Pyrrolo pyrazoles, 1,6-dihydro

The structure of dihydro-4,5-6//-pyrrolo[l,2-3]pyrazoles 23 and 24 have been determined by X-ray crystallography <2004BML3581>. 

An easy synthesis of the 2-oxo-2,3-dihydro-l/7-pyrrolo[l,2- ]pyrazole system can be performed by reaction of 1,2-diaza-1,3-butadienes 33 with dialkyl 1,3-acetonedicarboxylate 34 in the presence of potassium carbonate. At first, 1-aminopyrroles 36 was produced by dehydration in the presence of copper(n) trifluoromethanesulfonate. Treatment of these compounds with sodium hydride led to ATZ-substituted 2-oxo-2,3-dihydro-17/-pyrrolo[l,2-A]pyrazole 38. Under the same reaction conditions, and after acidic treatment, NH-BOC-protected 1-aminopyrrole was transformed to NH-unsubstituted 2-oxo-2,3-dihydro-l//-pyrrolo[l,2-A]pyrazole 37 (BOC =/-butylcarbonyl) (Scheme 1). 

While cycloaddition approaches have been discussed extensively in this chapter, there are certain substitution patterns that are not amendable to such approaches. In these cases, the more traditional annelative approaches are necessary. For example, the 5,6-dihydropyrrolo[3,4-rf]imidazol-4(3//)-one (286) is obtained from the diamine (285) and triethyl orthoformate. If formamide is used in excess, 6-(formamidomethylene)-5,6-dihydropyrrolo[3,4-d]imidazol-4(3//)-one (287) is obtained (Scheme 53) <70JPS1732>. A variant of the Thorpe cyclization was employed in the preparation of 3-amino-4//-pyrrolo[3,4-c]isoxazoles (289) from a-cyanooximes (288) (Equation (66)) <68JMC453>. 3-Acyltetramic acid (290 X = NR2) and 3-acyltetronic acid (292 X = O) hydrazones undergo ready cyclization in refluxing xylene with catalytic p-toluenesulfonic acid to afford 4-oxo-l,4-dihydro-6/f-pyrrolo[3,4-c]pyrazoles (291) and 4-oxo-l,4-dihydro-6//-furo[3,4-c]pyrazoles (293), respectively (Equation (67)) <82SC43l>. The novel synthesis of 5-amino-6a-hydroxydihydro-6//-pyrrolo[2,3-j]isoxazole (296) from 3,4-disubstituted 4-(amino)isoxazol-(4//)-ones (294) is hypothesized to occur by the cyclization of the ketene aminal intermediates (295) (Scheme 54) <91S127>. 

Condensation of acetyl-tetronic or -tetramic acids with methyl- or phenyl-hydrazine leads to 3-(l-hydrazinoethyl)-tetronic and -tetramic add, respectively, which upon dehydration form 1-substituted 4-oxo-l,4-dihydro-6//-furo[3,4-c]pyrazoles (X=0) and -pyrrolo[3,4-c]pyrazoles (X=NH) (equation 20) (82SC431). 

Phenyl-5,6-dihydro-4H- < pyrrolo-[1,2-b]pyrazol) (Withasomnin)107 Schmp. 117-118,5°... 

Four examples of the pyrrolo[l,2-ft]pyrazole nucleus are described 5,6-dihydro-4//- <83TL1067, 85SC259), l,2,5,6-tetrahydro-4Ff-, 3a,4,5,6-tetrahydro-3//-<83TLi067>, and 6-oxo- <87JCS(P1)653, 87JCS(P1)657>. 

Proton NMR data of a series of 5,6-dihydro-4 f-pyrrolo[l,2-b]pyrazoles (25) have been described in a paper related to synthesis of the alkaloid withasomnine (R = Ph, R = H) <83TL1067>, and are collected in Table 2. 

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