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The reaction of 1-ethoxycarbonylmethylpyridinium bromides 5a-k with nitro ketene dithioacetal, 1,1-bis(methylthio)-2-nitroethylene (2), in the presence of triethylamine in ethanol gave the desired ethyl 2-methylthioindolizine-3-carboxylates 3a-k in good y

We have determined the rates of acid-catalysed detritiation of the 1-positions of azulene and cyclazine in Aristar acetic acid at 70 deg C.From the known exchange rate ratio between this acid and trifluoroacetic acid at 70 deg C (1.58E8), the partial rate factors for exchange under the latter (standard) conditions are 9.93E13 and 4.34E13, respectively, yielding corresponding ?+ values of -1.60 and -1.56.From the literature rates of deuteriation of indolizine (1- and 3-position), N-methylisoindole (1-position), indole (3-position), and 6-methylpyrrolothiazole (7- and 5-position), partial rate factors under standard conditions may be calculated as 1.95E16, 9.93E16, 6.62E17, 5.52E13, 1.19E17, and 1.68E18, respectively.The corresponding ?+ values are -1.86, -1.94, -2.04, -1.57, -1.95, and -2.08.N-Methylisoindole appears to be the most reactive aromatic compound known.The extreme reactivity of these compounds (indole apart) is attributed to creation of aromaticity in their respective transition states, and is reflected in very small methyl substituent effects as required by the reactivity-selectivity principle.Decomposition at higher acidities prevented determination of rate data for any other sites in azulene or cyclazine but maximum ?+ values for the 2- and 5-8-sites in indolizine may be estimated from literature data to be -1.57 and -1.30, respectively.The reactivity of the 3-position of indole is less than that of the 2-position in pyrrole (?2+ -1.70) as in acetylation.In acetic acid at 50 deg C trans-9,10-dimethyldihydropyrene underwent decomposition at a rate comparable to that of detritiation and no reliable rate data could be determined.Valence Bond Theory provides an easily visualized explanation of positional reactivities.It shows the origin of the reactivity of the most reactive site, and accounts for the relative reactivities of N-methylisoindole, indolizine, and cyclazine, and the positional reactivities in each of the latter two molecules as well as in azulene and 6-methylpyrrolothiazole.It accounts for differences in methyl substituent effects in some of the title molecules, for the predominant 1-substitution in formylation of imidazopyridine (previously considered anomalous), for the exclusive 3-bromination of 2-phenyl-2H-indazole, and shows that nitration of thienopyridopyrazolopyrimidine must take place at the 2- and not the 1-position recently reported.It also accounts for the 1-substitution in azupyrene, and the protonation of pyrrolopyridazine at C-1 in contrast to both theoretical (MO) predictions and the results for the isomeric azaindoles.

The reaction of 3H-pyrrolizines 3 with vinamidinium salts 4 provides a new and generally applicable route to cyclazines 5.Pyrrolizinefulvenes are intermediates of this reaction as shown using 3f as an example. - Cyclopentacyclazines 11 were prepared from the hitherto unknown 3H-pyrrolizines 3b, c, d and the pyrrolizine esters 3e, f with the cyclopentadiene iminium salt 10 under conditions which have been described previously.Additional evidence for a close similarity between cyclazines 11 and the corresponding azulenes has been obtained from the UV spectra of 11.

3H-Pyrrolizine reacts with NN-dimethylformamide and phosphoryl chloride to give a 3-(NN-dimethylaminomethylene)-3H,5H-pyrrolizinium salt (2), isolated as the perchlorate, which can be further converted, with NN-dimethylthioformamide and acetic anhydride, into 3,5-bis-(NN-dimethylaminomethylene)-3H,5H-pyrrolizinium perchlorate (8).The conjugate base of the salt (2) reacts with dimethyl but-2-yne-1,4-dioate to give dimethyl pyrroloindolizine-5,6-dicarboxylate.The salt (8) reacts with nitromethane, in the presence of base, to give 6-nitropyrroloindolizine (9a) and with ammonia to give pyrazinopyrrolizine (10a).Electrophilic substitution reactions of (9a) and (10a), and nucleophilic substitution of (10a), are described.