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The IR spectra in the hydroxyl group stretching vibration region of the simplest hydroxyalkylpyrrolizidines have been examined. The spectra were taken in the form of pure liquids, dilute solutions in carbon tetrachloride, and for individual bases in the gas phase. It was shown that in dilute solutions ΔνOH depends on the geometric parameters of the intramolecular hydrogen bond (IMHB). The energy of the IMHB of 3-(2-hydroxyethyl)pyrrolizidine was measured in dilute solution and in the gas phase.

The cis-trans conversion in pyrrolizidines and the deciding effect of steric factors on their conformational equilibrium are discussed. Work on the synthesis and characteristics of sterically strained pyrrolizidines is analyzed and discussed. It is shown that such compounds (predominantly trans-fused) have a series of features in their properties that greatly distinguish them from unstrained pyrrolizidines. The first results from study of the thermodynamics of cis-trans conversion of the pyrrolizidine bicycle are summarized.

Data have been summarized of several studies on the separation of isomeric pyrrolizidine alcohols by GLC using liquid polar stationary phases. It was shown that the order of emergence of isomers from the chromatographic column is determined to a significant extent by competition of intermolecular hydrogen bonds formed in the sorbate-sorbent systems and intramolecular hydrogen bonds in the molecules of the same pyrrolizidine alcohols. The preference for one or other type of hydrogen bond depends on the stereochemistry of the pyrrolizidine alcohols. Analysis of the geometric conditions for the formation of intramolecular hydrogen bonds in the investigated compounds in conjunction with chromatographic resolution data enables their configurations to be assigned. The anomalously short retention times of highly strained 5-hydroxyalkyl-3-methylpyrrolizidines are explained by the existence in them of a bicyclic conformation predominantly with a trans linkage and with f avora ble geometric conditions for forming intramolecular hydrogen bonds in them.

A simple method for the synthesis of 5,5-dimethyl-4-cyanomethylene-2-cyanomethyl-2-[1-methyl-1-(carbamoyloxy)ethyl]-1,3-dithiolanes was developed on the basis of the reaction of 5,5-dimethyl-4-cyanomethylene-1,3-oxathiolan-2-one with amines (primary and secondary) and ammonia.

Known methods for the synthesis of 1,2-dihydropyrrolizines are presented in a systematized form. Literature data on the chemical properties of 1,2-dihydropyrrolizines are summarized and correlated; and synthetic, physiologically active substances belonging to this group of compounds are examined critically.

13C NMR spectra were obtained for pyrrolizidinium salts and their homologs and their signals were assigned. With the exception of highly strained cis-3,8-H-cis-5,8-H-3,5-dimethylpyrrolizidine (VI), all the bases studied upon their direct mixing with CF3CO2H form salts only with cis-fused rings in the cation. Mixtures of salts with cis- and trans-fused pyrrolizidinium fragments are formed upon the reaction of cis-3,8-H-methy1- (III) and cis-3,8-H-cis-5,8-H-3,5-dimethylpyrrolizidine (VI) under conditions close to those for kinetically-controlled amine protonation. The13C NHR spectra of the isomeric pyrrolizidinium salts obtained as a result of the absorption of base VI by sulfuric acid were used to evaluate the conformational equilibrium in the starting compound VI. The13C NMR chemical shifts of unsubstituted trans-fused pyrrolizidinium salts were predicted.

Substituted 1,3-thiazinoazoles were obtained by treating benzimidazole-2-thione, 4,5-diphenylimidazole-2-thione, and 1,2,4-triazole-3-thione with tertiary cyanoacetylenic alcohols and their acetals in the presence of lithium hydroxide. Treatment of the 1,3-thiazinobenzimidazoles with base destroyed the thiazino ring forming benzimidazol-2-one.

1-(2-Furyl)-3-amino-4,4-dimethylpentane was used to obtain 3-tert-butyl-1,2-dihydropyrrolizine, the catalytic hydrogenation of which over Rh/Al2O3 at room temperature gives a mixture of cis- and trans-3,8-H-3-ter-butylpyrrolizidines with predominance of the cis isomer, whereas hydrogenation at 90–100 °C gives a mixture containing the trans isomer as the principal component. The three-dimensional structures of the isomers follow from data on the catalytic hydrogenation and isomerization and the IR, Raman, and PME spectra. A considerable percentage of the trans-fused form is characteristic for cis-3,8-H-3-tert-butylpyrrolizidine.

The basicities of pyrrolizidine and its homologs in aqueous and aqueous acetonitrile solutions at 25 ° C were determined. It is shown that among 3-alkylpyrrolizidines, the isomers with cis configurations have higher pKa values than the isomers with trans configurations. On the basis of a comparative study of the 1H and 13C NMR spectra it was concluded that cis-3,8-H-cis-5,8-H-3,5-dimethylpyrrolizidine in aqueous solutions exists chiefly in the trans-fused form, whereas conformationally heterogeneous pyrrolizidines with primarily cis-fused rings experience a shift of the equilibrium to favor an increase in the cis-fused conformations when a nonpolar solvent is replaced by a polar solvent. The basicity of the trans-fused conformation of pyrrolizidine is predicted on the basis of the data obtained.

Nitration of 1,2-dihydropyrrolizine and its homologs with a mixture of nitric acid and acetic anhydride has been shown to give a mixture of 5-, 6-, and 7-nitro-1,2-dihydropyrrolizines. The distribution of isomers with respect to the position of alkyl substituents in the nonaromatic portion of the bicyclic is discussed.

Mixtures of isomeric 5-, 6-, and 7-carbethoxymethyl-1,2-dihydropyrrolizines were obtained by reaction of 1,2-dihydropyrrolizines with ethyl diazoacetate. The effect of the position of the alkyl groups in the two-membered ring on the ratio of isomers in the reaction products is demonstrated. A method for the isolation of 5-carbethoxymethyl-1,2-dihydropyrrolizines from the mixtures of isomers based on the difference in their reactivities in diazo coupling is described. The preferred conformations of the two-membered rings in the 5-carbethoxymethyl-1,2-dihydropyrrolizines are judged from the PMR spectral data.

The enthalpy of the cis-trans conversion of quinolizidine was calculated by two independent methods on the basis of the literature data on the heat content of decalins, the difference in the enthalpies of the N-H-axial and N-H-equatorial conformations of piperidine, and the hydrogen bond energies in the quinuclidine-phenol and quinolizidine-phenol systems. The calculations yielded ΔH values of 3.7 and 4.3 kcal/mole for gaseous quinolizidine and 3.3 kcal/mole in favor of the trans-fused form for the liquid.

The reaction of phenylcyanoacetylene with imidazolethiones was studied. It is shown that in the presence of 5–10% KOH the addition of phenylcyanoacetylene is accompanied by intramolecular cyclization with the formation of imidazo-1,3-thiazines. An increase in the amount of catalyst to 20% leads to cleavage of the thiazine ring at the C-S bond and the formation of the corresponding acrylonitrile derivatives. Products of addition of 2 moles of phenylcyanoacetylene were obtained.

The conditions for carrying out the condensation of 1,2-dihydropyrrolizine, 2-methyl-1,2-dihydropyrrolizine, and 3-methyl-1,2-dihydropyrrolizine with ethylene oxide were investigated. The NMR spectra indicated that hydroxyethylation proceeds at the 5 and 7 positions of the 1,2-dihydropyrrolizine system.

The stereochemistry of the catalytic hydrogenation of 5- and 7-(β-hydroxyethyl)-1,2-dihydropyrrolizines on 2.5% Rh/Al2O3 and Raney nickel under various conditions has been studied. On the basis of information on the configurational catalytic isomerization and the competing quaternization of the isomers, a consideration of the relative retention times, and an analysis of the geometries of the molecules of the 1- and 3-(β-hydroxyethyl)pyrrolizidines a configurational assignment of the stereoisomers has been made.

The selectivity of the position of nitration of 1-methylpyrrole, 1,2-dimethylpyrrole, 1,2-dihydropyrrolizine, and 5,6,7,8-tetrahydropyrrocoline was found. In contrast to the selectivity of substitution during nitration of their carbocyclic analogs, o-xylene, indane and tetraline, the fraction of the α-nitro-isomer in the nitration products of 1,2-dimethylpyrrole is smaller than the fraction of α-nitro derivatives of 1,2-dihydropyrrolizine and 5,6,7,8-tetrahydropyrrocoline, and in the two latter cases the isomers are almost equally distributed. During nitration of the above bicyclic pyrroles, the Mills-Nixon effect does not appreciably influence the selectivity of the position of the reaction.

1,2,4-Triazolo[3,2-b]-1,3-thiazines were obtained by the reaction of 1,2,4,-triazole-3-thiones with an equimolar amount of 1-phenyl-2-cyanoacetylene in the presence of triethylamine or potassium hydroxide. It is shown that triazolethiones form N,S diadducts upon reaction with a twofold excess of cyanoacetylene. The nature of the heteroatom in the exo position of the heteroring affects the direction of addition to phenylcyanoacetylene. 2,4-Bis(1-phenyl-2-cyanovinylene)-1,2,4-triazol-3-one was synthesized.

Furan and tetrahydrofuran amines with the amino group at position 4 or 5 in the side chain are intramolecularly dehydrated to the corresponding 1-azabicyclo compounds when passed over Al2O3-ZrO2 catalyst at 325–330°.

The composition of mixtures of epimeric 3-methylpyrrolizidines obtained by four methods was determined by gas-liquid chromatography (GLC). The data presented make it possible to select a method for the preparation of a mixture of isomers of 3-methylpyrrolizidine with predominance of trans- or cis-3,8-H-3-methylpyrrolizidine.

Opening of the 1,3-oxathiolane ring with the formation of 8-mercaptoalkylcarbamate II evidently occurs in the first step under the influence of the amine; the subsequent dimerization of II via the addition of the mercapto group of one molecule to the double bond of a second molecule leads to intermediate III. This is followed by intramolecular substitution of the carbamoyl grouping with the formation of the 1,3-dithiolane ring.

During the reaction of l-cyano-3-methyl-3-hydroxy-l-pentyne (I) with Na2S'9H20 in the presence of potassium hydroxide (in the ratio of 0.4:1:1; 20~ dioxane), 2-methyl-2-ethyl3,4-di(cyanomethylene)oxetane (III), a product of the autoheterocyclization of carbinol I, was obtained instead Of the expected sulfide according to [i]. It is possible that cyanoethylene, formed as the result of the inverse Favorski reaction, is added in the form of an anion to the triple bond of the initial carbinol, which is very electrophilic in character. Then, the intermediate carbinol II cyclizes into III in a yield of 55%, mp 89~ (from ether). IR spectrum (KBr): 1650 (C----CH), 2220 cm -~ (CN); PMR spectrum (i00 MHz, CDCI3): 1.65 (s, 2-CH~); 1.20 (t, 2-CH2-CH3) and 1.88 (qu, 2-CH2); 5.55 (s, 3'-CH); 5.13 ppm (s, 4'-CH), f3',4' = 0.6 Hz.

In order to study the reaction mechanism of the catalytic intramolecular conversion of heterocycles [1–3] and to broaden the field of their application, we have studied the dehydration over Al2O3 of 1-amino-3-(α-tetrahydrofuryl) propane (I), 1-methylamino-1-(α-tetrahydrofuryl) propane (II), and 2-(3-hydroxy-1-propyl)-1-methylpyrrolidine (III), leading in all three cases to pyrrolizidine (IV).