Conversion of pyrrolo[1,2-?]pyrazinium salts to 8-aminoindolizines

Butkevich

Иванов

2006

Chem Heterocycl Compd

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The pyrrolo[1,2-a]pyrazine system is relatively stable against the action of weak electrophiles, as shown by the fact that 6-acetylpyrrolo[1,2-a]pyrazine is formed with a yield of only 16% when unsubstituted pyrrolo[1,2-a]pyrazine is boiled with an excess of acetic anhydride for 24 h [1].While studying the acetylation of 1-methylpyrrolo[1,2-a]pyrazine (1a) and 1,6-dimethylpyrrolo[1,2-a]-pyrazine (1b), in addition to the products from substitution of the pyrrole ring, we quite unexpectedly obtained the products from the cross-linking of two molecules of the heterocycle.

mentioning

confidence: 99%

Dimerization of 1-methyl-substituted pyrrolo[1,2-a]pyrazines during acetylation

Butkevich

Иванов

2006

Chem Heterocycl Compd

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“…The reaction course was monitored by thin-layer chromatography on Silufol UV-254 plates. Starting pyrrolo[1,2-a]pyrazines 1-10 were prepared according to our previous procedure [10].…”

Section: Methodsmentioning

confidence: 99%

Trifluoroacetylation of pyrrolo[1,2-a]pyrazines

Kabanova

Tselishcheva

et al. 2007

Chem Heterocycl Comp

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A study was carried out on the reaction of pyrrolo [1,2-a]pyrazines containing an alkyl, aryl, or aralkyl substituent at C-1 with trifluoroacetic anhydride. Trifluoroacetylation products may be formed either by reaction in the pyrrole ring or at the aryl or aralkyl groups at C-1. Products of electrophilic substitution at C-6 are formed in the trifluoroacetylation of pyrrolo [1,2-a]pyrazines containing at C-1 a substituent bulkier than a methyl group but lacking substituents at C-6 (the α-position of the pyrrole ring).The pyrrolo[1,2-a]pyrazine bicyclic aromatic system has not been studied extensively, perhaps due to the difficulties in its preparation and its relatively low reactivity. The relative stability of the pyrrolo[1,2-a]pyrazine system to the action of weak electrophilic agents is indicated, for example, by the formation of the 6-acetyl derivative in only 16% yield upon heating 1,7-dimethylpyrrolo[1,2-a]pyrazine with excess acetic anhydride at reflux for 24 h [1]. The bromination of unsubstituted pyrrolo[1,2-a]pyrazine leads to a 1:1 mixture of 8-bromo and 6,8-dibromo derivatives [2, 3], while formylation of this model leads to 8-formylpyrrolo[1,2-a]pyrazine in 60% yield as the authors [2] affirm, although the 1 H NMR spectrum given for this compound leaves doubt concerning its structural identification. Paudler and Dunham [3] were unable to formylate unsubstituted pyrrolo[1,2-a]pyrazine by the Vilsmeier-Haack procedure. Attempts to obtain nitroso or azo derivatives of pyrrolo[1,2-a]pyrazines in reactions with nitrous acid and phenyldiazonium chloride also proved unsuccessful [4].Hence, we undertook a systematic study of the behavior of pyrrolo[1,2-a]pyrazines 1-10 in reactions with electrophiles such as acylation with trifluoroacetic anhydride, which is a stronger acylating agent than acetic anhydride. The trifluoroacetyl cation is a rather strong electrophile. Thus, the acylation of pyrroles by trifluoroacetic anhydride proceeds rapidly at 0°C [5]. In previous work [6], we showed that dipyrrolo[1,2-a:2',1'-c]pyrazines form ditrifluoroacetyl derivatives as the major reaction products with excess trifluoroacetic anhydride even at room temperature. On the other hand, much more complicated behavior is found for 3,4-dihydropyrrolo[1,2-a]pyrazines, for which the direction of the reaction depends on the structure of the starting compounds and substrate/reagent ratio [7].The α-position of the pyrrole ring in 1-methylpyrrolo[1,2-a]pyrazine (1) is unoccupied and we might expect that the most likely product in its reaction with trifluoroacetic anhydride would be 6-trifluoroacetylpyrrolo[1,2-a]pyrazine by analogy to acylation by acetic anhydride [1]. However, the reaction of 1 with a 2.5-fold excess of trifluoroacetic anhydride in benzene (method A) yielded three products. NMR spectroscopy and mass spectrometry indicated the formation of 1-(3,3,3-trifluoro-2-oxopropylidene)-__________________________________________________________________________________________ M. V. Lomonosov

“…The course of the reaction was monitored by TLC on Silufol UV-254 plates. The starting pyrrolo [1,2-a]pyrazines were synthesized by the procedure in [5]. The physicochemical and spectral characteristics of the compounds obtained are presented in Tables 1-3.…”

Section: Methodsmentioning

confidence: 99%

Nitration of Pyrrolo[1,2-a]pyrazines

Butkevich

Плешкова

2005

Chem Heterocycl Compd

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Pyrrolodiazine derivatives have attracted the attention of researchers because they have a broad spectrum of physiological activity. Azole and azine moieties are encountered in many natural biologically active compounds such as alkaloids and biogenic amines. The bicyclic aromatic system of pyrrolo[1,2-a]pyrazine has been poorly studied due to the relative difficulty of obtaining it, its low reactivity relative to electrophiles, and also the ambiguous reaction pathways of these compounds [1]. The relative stability of the pyrrolo[1,2-a]pyrazine system with respect to treatment with weak electrophilic reagents is suggested by the fact that the unsubstituted pyrrolo[1,2-a]pyrazine, when boiled with excess acetic anhydride for 24 h, forms 6-acetylpyrrolo[1,2-a]pyrazine in only 16% yield [2].Earlier we studied the nitration reaction for asymmetrically substituted dipyrrolo[1,2-a;2',1'-c]pyrazine systems. Nitration was carried out by treatment with a mixture of nitric acid (d = 1.42 g/ml) and acetic anhydride at -10°C. The nitronium ion attacks the free α-position of the pyrrole ring to form the mononitro and dinitro derivatives [3].We have studied nitration reactions of pyrrolo[1,2-a]pyrazines containing alkyl and aralkyl substituents at the 1 and 6 positions of the heterocycle when treated with a nitrating mixture, with acetyl nitrate, and with nitric acid. N N R N N R O 2 N N N R NO 2 N N R NO 2 O 2 N HNO 3 conc. H 2 SO 4 1a-d 2a-d 3a-d 4a-d + + + 1-4 a R = Me; b R = Et; c R = Pr; d R = i-Pr __________________________________________________________________________________________ 1 M.