Pyrrolo quinoxalines reactions

Interesting constructs of molecules such as pyrrolo-pyridines, pyrrolo-quinolines, pyrrolo-pyrazines, pyrrolo-quinoxalines and pyrrolo-pyrimidines could be constructed by intramolecular Chichibain-type reaction. Davis and co-workers were the first to show the first of these examples, where p-methylazines react with nitriles to give the corresponding fused bicycle in the presence of excess base (2.5 equiv). For example, P-picoline reacts with benzonitrile in the presence of LDA to give the pyrrolo-pyridine adduct 61 in a 90% yield and traces of 62a. Under similar conditions and if... 

A Cu-catalyzed domino reaction has been developed by Cacchi and his group [305] for the synthesis of pyrrolo[2,3-b]quinoxalines 6/4-101 using a 2-bromo-3-tri-fluoroacetamido quinoxaline 6/4-98 and a tolane 6/4-99 containing electron-donating or -withdrawing groups as substrates, and with 6/4-100 as a proposed intermediate (Scheme 6/4.24). 

Quinoxaline and 2-methylquinoxaline form 1 1 adducts (111) with diphenylcyclopropenone,122 and an analogous pyrrolo[l,2-a]quin-oxaline has been isolated from the reaction of quinoxaline with di-phenylcyclopropenethione.123... 

Vilsmeier reaction, 4, 1051 Furo[3,2-6]pyrroles MO calculations, 6, 979 synthesis, 4, 1069 6, 1009 Furo[3,4-a]pyrrolo[2,1,5-cd]indolizine nomenclature, 1, 22 Furopyrylium salts, 4, 993-995 Furoquinolines biosynthesis, 4, 992 occurrence, 4, 988 pharmacology, 4, 992 reactions, 4, 988 synthesis, 4, 989 Furo[3,2-c]quinolines, 4, 991 Furo[3,4-fe]quinoxaline, 1,3-diphenyl-synthesis, 4, 993 Furoquinoxalines, 4, 992 Furo[2,3-6]quinoxalines synthesis, 4, 992 Furosemide toxicity, 1, 136 Furospinulosin UV spectra, 4, 587 Furospongin-I mass spectrometry, 4, 583 Furo[3,4-d][l,2,3]triazole, 2,6-dihydro-synthesis, 6, 996 Furo[3,4 -d][ 1,2,3]triazoles synthesis, 6, 996 Furoxan, 4-amino-3-aryl-tautomerism, 6, 404 Furoxan, 4-amino-3-methyl-synthesis, 4, 414 Furoxan, 4-aryl-3-methyl-rearrangement, 6, 408 Furoxan, 3-aryl-4-nitro-synthesis, 6, 414 Furoxan, 4-benzoyl-3-methyl-oxime... 

There is a paucity of functional group reactions associated with the pyrrolopyrazines. A few examples may be found within the references describing their syntheses. However, a reaction has been reported which describes the [4 + 2] cycloaddition of pyrrolopyrazines. Ring expansion of 2-phenyl-2//-pyrrolo[3,4-/ ]pyrazine (32) occurs through cyclocondensation of the trimethylsilyl ether (33) with, amongst other dienophiles, methyl acrylate, and a mixture of quinoxalines (34) is obtained in 38% yield (Scheme 2) <86JHC1641>. 

It is interesting to note that, due to the reversible character of the cycloaddition, isomerization favoring the product which is thermodynamically more stable may occur and an appropriate side-chain substituent may participate. For example, the thiazolo [4,5-b] quinoxalines 55, formed in the reaction of quinoxalinium salts with thioamides under kinetically controlled conditions, are able to undergo two different isomerizations (Scheme 45). When compound 55 contains an aryl group at C-2 (R2 = aryl) and this compound is heated in an ethanolic solution, the thiazoloquinoxaline 57 is formed. In the case of R2 = CH3, the methyl group participates in the isomerization process, yielding pyrrolo [2,3-b]quinoxalin-2-thione 58 (Scheme 45) (85KGS396). 

Nitrogen Heterocycles.- Reactions of iminophosphoranes have been used to prepare a wide range of heterocycles. Examples of compounds prepared by intramolecular aza-Wittig reactions include 3,4-dihydroquinazolines (191) and quinazolines (192), quinazoline derivatives (e.g. 193),pyrrolo( 1,2-a)quinoxalines (194), indolo[3,2-clquinolines (195), and indolo[l,2-c]quinazolines (196),"8 imidazolinones (197),"9 quinazolinones (198),"9, 120 pyrido[2,3-d]pyrimidine derivatives (199), 21 and 4,5-dihydropyrazolo(3,4-d]pyrimidine derivatives (200). 22 Tributyl(cyclohepta-1,3,5-trienylimino)phosphorane (201), prepared by thermal isomerization of the 2,4,6-derivative, reacts with a,p-unsaturated ketones to give 9H-cyclohepta[b]pyridine derivatives (202). 23 a synthesis of (2,4)pyridinophanes (204) by the reaction of N-vinyliminophosphoranes (203) with a,P-unsaturated ketones has been reported. 24... 

Kobayashi, K., Matoba, T., Irisawa, S., Matsumoto, T., Morikawa, O., Konishi, H. Synthesis of pyrrolo[1,2-a]quinoxaline and its 4-(1-hydroxyalkyl) derivatives by Lewis acid-catalyzed reactions of 1-(2-isocyanophenyl)pyrrole. Chem. Lett. 1998, 551-552. 

Several different approaches have been adopted for the synthesis of pyrrolo[l,2-a]quinoxalines. Particularly useful are approaches involving cyclization reactions of o-aminophenylpyrroles. Alternative syntheses have involved the use of o-phenylenediamine, the cyclization of /3-quinoxalinylpropionic acids, quaternization of quinoxaline derivatives, as well as several other routes less amenable to classification. 

Routes via o-aminophenylpyrroles present the most convenient syntheses of a wide variety of pyrrolo[l,2-a]quinoxalines. Thus reaction of the amino compound 6 with acetic anhydride in acetic acid gave the acetamido derivative which was cyclized with phosphoryl chloride to give the 4-methyl compound 7 (R = Me) in 56% yield. The 4-phenyl compound 7 (R = Ph) has been prepared similarly. An even more convenient synthesis of 4-aryl compounds is achieved by reaction of compound 6 with aromatic aldehydes to give the 4,5-dihydro derivatives These are readily oxidized to 4-arylpyrrolo[l,2-a]quinoxalines 9 with manganese dioxide. This approach may be carried out in one step by reaction of compound 6 with aromatic aldehydes (e.g., benzaldehyde) in the presence of cupric acetate. Reaction of the aminophenylpyrrole 6 with 90% formic acid gave pyrrolo[l,2-a]quinoxaline (7, R = H) directly in 98% yield. Pyrrolo[l,2-a]quinoxalines substituted in the l-position and the 7-position have also been prepared from appropriately substituted... 

The adduct 14, from the reaction of the amino compound 6 with dimethyl acetylenedicarboxylate, was cyclized to the pyrrolo[l,2-a]quinoxaline 15 using polyphosphoric acid. The anilino compound 17... 

A 1,5-dihydro-l-oxo derivative (47) of pyrrolo[l,2-a]quinoxaline has been shown to be the product of a supposed Diels-Alder reaction between 2,3-dimethylquinoxaline (46) and maleic anhydride. 2-Methylquinoxaline and 2-methyl-3-phenylquinoxaline give the corresponding derivatives 48. " The reaction between 2,3-dimethyl quinoxaline and maleic anhydride proceeds in 80% yield when the reactants are fused together. " ... 

Reaction of the 8-diketone 78 with ethyl orthoformate did not give the hoped for pyrano[2,3-h]quinoxaline 79 but gave a mixture of the pyrrolo[l,2-a]quinoxalines 80. ... 

Pyrrolo[l,2-a]quinoxaline undergoes smooth electrophilic substitution. The distribution of products obtained depends on the size of the incoming electrophile, as with bulky reagents steric interactions tend to inhibit reaction at the most electron-rich carbon-1 atom." Theoretical calculations predict that the most favored positions for electrophilic substitution, in decreasing order of susceptibility, are 1>3>6>2. Reports have appeared describing electrophilic substitution at the 1,3- and 2-positions, but no reaction at the 6-position has yet been observed. 

Nitration of pyrrolo[l,2-a]quinoxaline by adding a mixture of the compound and potassium nitrate to concentrated sulfuric acid yields a mixture of 25% 1-nitro and 48% 3-nitro derivatives. No significant reaction was observed with potassium nitrate in trifluoroacetic acid, or in fuming nitric acid alone or fuming nitric acid and acetic anhydride." The attempts to avoid the use of sulfuric acid were made because of the ease with which the heterocycle undergoes sulfonation. Thus treatment with concentrated sulfuric acid at room temperature readily gave the 3-sulfonic acid. Apparently the electrophile is too large to allow formation of detectable amounts of the isomeric 1-sulfonic acid. The 1-methyl and... 

Reaction of pyrrolo[l,2-a]quinoxaline with potassium amide in liquid ammonia affords the 4-amino derivative in 56% yield. Treatment of the... 

Miscellaneous Mn02-mediated Reactions. Treatment of a quinoxalinium salt with various alkenes in the presence of Mn02 has been found to effect a novel 1,3-dipolar cycloaddition reaction to give the corresponding pyrrolo[l,2-a]quinoxalines (eq 65). ... 

Cyclization of the quinoxaline chloride 50 to prepare pyrrolo[2,3-f ]quinoxaline under usual conditions is slow and the yield is low, because the aminoquinoxa-lines are strong chelating agents and poison Pd catalysts. However, the locked Pd catalyst is released and the reaction proceeds smoothly under Jeffery s ligandless conditions to give the pyrrolo[2,3- ]quinoxaline 51 in 67 % yield [38]. 

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