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Notes: The products of the thermolysis of N-(1-pyridinio)-2-nitroanilides (1) had previously been interpreted as tris (2-nitrophenyl)-triaziridines (3). The present work shows them to be actually 1, 2-bis[(Z)-(2′-nitrophenyl)-ONN-azoxy]benzenes (5). The revised structural assignment is based on the chemical and the spectroscopic (especially 1H-NMR.) properties of 5 and on the results of a X-ray structural analysis.

Notes: Triaziridines. II. First Examples: Alkyl 2,3-Dialkyl-triaziridine-1-carboxylatesThe first examples of substituted triaziridines 2 are described; they carry an alkoxycarbonyl and two alkyl groups (as in 4). The preparation of these novel threemembered nitrogen homocycles was achieved by photolysis of 1-alkoxycarbonylazimines 3c. In this way, methyl 2, 3-(cis-1, 3-cyclopentylene)triaziridine-1-carboxylate (6a), methyl trans-2, 3-diisopropyl-triaziridine- 1 -carboxylate (8a) and their ethyl ester analogues 6b and 8b were obtained in 50, 18, 65 and 21 % yield, respectively. The structure of the triaziridines 6 and 8 was deduced from their spectroscopic properties which reveal several interesting features: 1) N (2) and N (3), carrying alkyl groups, are pyramidal and invert slowly; 2) the isopropyl groups of 8 are situated trans to each other on the three-membered ring, whereas the two alkyl groups of 6 are cis as forced by the C-ring system; 3) N (1) is also pyramidal, despite its «amidic» nature; it inverts with an activation energy of 62 (± 4) kJ/mol; 4) the alkoxycarbonyl, group does not conjugate with N (1) and rotates rapidly.The triaziridines 6 and 8 are thermally labile, isomerizing slowly at room temperature into the corresponding azimines 5 and 7 by cleavage of one of the bonds to N (1 ). The velocity of this ring opening reaction is almost the same for 6 and 8, so that a dependence on the relative configuration at N (2) and N (3) is not evident. The Arrhenius activation energy for the isornerization of 6a to the corresponding azimine 5a and the enthalpy difference between 6a and 5a were both determined as 100 (± 4) kJ/mol.The photolysis of 1-alkoxycarbonyl-2, 3-diisopropyl-azimines (7) in diethyl ether was accompanied by a side reaction leading to methyl and ethyl N-(1-ethoxyethyl)carbamate (9a and 9b, resp.), presumably by insertion of the alkoxycarbonylnitrene, generated by photofragmentation of the azimines, into the ethereal solvent.

Notes: Triaziridines. Synthesis of cis-2,3-Diisopropyltriaziridine-1-carboxylic EstersIrradiation of the (Z)-azimines 1a, b in Et2O with a Hg high pressure lamp through Corex yielded (besides 30% of the previously described trans-triaziridines 3a, b) 15% of the new cis-triaziridines 4a, b. The same irradiation of the (E)-azimines 2a, b afforded only 15-18% of 3a, b but 20-23% of 4a, b. Thus, these azimine photocyclizations show some stereospecificity. The triaziridines 3a, b and 4a, b formed in this way were always accompanied by the same three types of by-products, namely 10-15% of the ‘triazones’ 5a, b, 11-20% of the carbamic esters 6a, b, and 5-10% of the ether/nitrene insertion products 7a, b. The constitution and configuration of the new cis-triaziridines 4 followed from their spectral properties. Of particular interest are the symmetry properties of 4 derived from the 1H-, 13C-, and 15N-NMR spectra: The stereoisomers 3 and 4 differ only in that the isochronicity of the two constitutionally equivalent molecular halves is temperature dependent in 3 but independent in 4. Both triaziridines 3 and 4 exhibit the IR CO band at (for carbamates) remarkably high frequency. The results confirm that the alkyl-substituted N-atoms of triaziridines are pyramidally stable, that the corresponding acyl-substituted N-atoms (N(1)) are also pyramidal, but can invert more readily, and that rotation around the N(1), C(=O) bond is rapid. Thus, there can be only little amide-type delocalization between a triaziridine N-atom and an acyl substituent of the carbamate type attached to it.

Notes: Triaziridines. Ring Openings of TriaziridinesEleven triaziridine derivatives were heated at 60° in CDCl3 to obtain information on the tendency towards, resp. the resistance to, ring opening of the N3-homocycle by thermolysis. Among these triaziridines, there are three which contain, as one of the substituents, a methoxycarbonyl group (ester derivatives 1, 5 and 16), three a methyl group (methyl derivatives 18, 24, and 26), three an H-atom (14, 27, and 30), and two a negative charge (31 and 32). The other two substituents in each of these four classes of triaziridines are trans-located i-Pr groups (1, 18, 27, and 31), cis-located i-Pr groups (5, 24, 14, and 32), and a 1,3-cis-cyclopentylidene group (16, 26, and 30). As major products these mild thermolyses, we isolated : from the trans-ester 1 and from the annellated ester derivative 16, the 1-acyl-azimines 2 and 17, respectively, from the cis-ester 5, the 3-acyl-triazene 4, from the trans-methyl derivative 18, the (E)-diazene 19, and hexamine 21, from the cis-methyl derivative 24 the 2-methylazimine 25, both from the trans- and cis-H-derivatives 27, and 14, respectively, the H- triazene 13 and, finally, both from the trans-and cis-anion 31 and 32, respectively - after protonation the H-triazene 13 and - after methylation - the methyl-triazene 33. The same thermolysis of the annellated methyl and H-derivatives 26 and 30, respestively, resulted only in decomposition.These results can be uniformly interpreted with a primary opening of the triaziridine ring by rupture of one of the two types of N—N bonds lending to azimines or triazenide anions. Some of the azimines were isolable, namely 2, 17, and 25, and one was spectroscopically observable as an intermediate, namely 11 on the way to the triazene 4. The other azimines are plausible intermediates to the isolated products, namely 15 on the way to 13, and 22 on the way to 19 and 21. The triazenide anion 28 is the evident intermediate on the way to 13 or to 33. The annellated azimines are assumed not be formed from 26 and 30, or then to be be decomposed under the conditions of their formation. We conclude that the triaziridine derivatives 1, 16, and 18 underwent thermal ring opening between N(1) and N(2), while the derivatives 5, 14, 24, 27, 31, and 32 were ruptured between N(2) and N(3); no conclusion was possible on the ring opening of the derivatives 26 and 30.The predominant formation of the (Z)-azimine 2 from the trans-triaziridine 1, and of the (E)-isomer 3 - among the two azimines - from the cis-triaziridine 5 suggests a stereospecificity in the triaziridine ring openings. This would, however, not be expected to be observable in the products from the other triaziridines, since both N—N bonds of the azimine 25 and of the anion 28 probably rotate rapidly and since the secondary trans formations of the other primary products are not able to retain configurational information.

Notes: Stable Pyramidal configurations at the Nitrogen Atoms of Dialkyl-and Trialkyl-triaziridinesStereochemical features of the recently synthesized nine samples of di- and trialkyl-triaziridines, namely the 1,3-cyclopentylen-(series a) and the two stereoisomers of the diisopropyl derivatives (series b and c), containing as the third substituent an H-atom (2), a CH3 group (3)or a CH2OH group (4), were elaborated on the basis of the 1H-, 13C-, and 15N-NMR spectra. The three N-atoms of the saturated N3-homocycle were found to be stable to pyramidal inversion in all cases. According to their NMR spectra, 2-4 of the series a and b possess twofold symmetry (Cs), while 2-4 of series c are asymmetric. Thus, series c has the trans-configuration at N(2)/N(3) and, consequently, the cis-configuration at N(1)/N(2), while series a and b have the cis-configuration at N(2)/N(3) and -since the all-cis-arrangement is excluded-the trans-configuration at N(1)/N(2). The asymmetry of the trans-configurated 2c turned into twofold symmetry (C2), when a little CF3COOH was added. The 1H- and 13C-NMR data of series b and c of our alkyl-triaziridines exhibit a shielding effect, according to which there are two types of i-Pr groups, i-Pr(a) and i-Pr(b). They differ in the NMR signals of the H- and the C-atoms of their CH groups: the H-atoms of i-Pr(a) are more deshielded by 0.75-1.111 ppm and its C-atoms are more shielded by 10.0-160.0 ppm as compared to the corresponding atoms of i-Pr(b). i-Pr(a) is cis (on the N3-homocycle) to a large substituent (such as i-Pr, Me, CH2OH) and to a lone pair, while i-Pr(b)is cis only to a small (H) or to no substituent and to one or two lone pairs. An analogous effect appears in the NMR signals of the CH3 and CH2OH groups at N(1) of 3 and 4 in the series b and c.

Notes: On the Total Synthesis of BetalainsImproved total syntheses of the red-violet aglucone of the beet coloring matter and of the yellow cactus coloring matter indicaxanthine are presented. Formyl-olefination of the piperidone-diester 6 with the acetaldehyde synthon 5 led to the piperidylidene-acetaldehyde derivative 8, which was converted into the 2,4,4-trimethylsemicarbazone of rac-betalamic acid dimethyl ester (10) by treatment with t-BuOCl and then Et3N. Exchanging the semicarbazone moiety with the (S)-cyclodopa derivative 18, with (S)-proline (19) and with indoline (20) transformed 10 to betanidin (21/22), to indicaxantihin (23/24) and to rac-indo-betalaine (25), respectively. The latter, a new, relatively stable betalaine, was hydrolyzed and esterified to rac-betalamic acid dimethyl ester (29). Under the influence of NH3/MeOH, 26 (the dimethyl ester of 25) was dehydrogenated spontaneously to indo-neobetalaine dimethyl ester (27).Synthetic betanidin consisted of a 4:6 mixture of the (natural) (2S, 15S)- (21) and the (2S, 15R)-isomer (22) and both of a 75:25 mixture of the (E)- and the (Z)-isomer. Synthetic indicaxanthin (23/24) and the indo-betalaine (25) represented a 65:35 and a 70:30 mixture, respectively, of (E)- and the (Z)-isomers. All (E)- and (Z)-isomers are rapidly interconvertible. Temperature-dependent 1H-NMR-measurements of 25 established ΔG≠ = 84.7 kJ/mole for the (E)-to-(Z)-conversion.The t-BuOCl/NEt3 method for the introduction of an enaminic double bond was applied to the model transformations of the amines 6, 12 and 15 to the conjugated enamiens 11, 13 and 17, respectively.

Notes: Synthesis of 3-(2-Carboxy-4-pyridyl)-and 3-(6-Carboxy-3-pyridyl)-DL-alanineAs starting materials for potential photochemical approaches to betalaines C(R = COOH) and to muscaflavine F(R = COOH), β-(2-carboxy-4-pyridyl)- and β-(6(carboxy-3-pyridyl))-DL-alanine (A and D with R = COOH or 4 and 11), respectively, were prepared (Scheme 1). The synthesis of 4 (= A, R = COOH) started with the 2-[(4-pyridyl)methyl]malonate 1 and proceeded via the N-oxide 2, cyanation and hydrolysis (Scheme 2). Amino acid 11 was obtained from (3-pyridyl)methyl-bromide (6) via the malonate 7 by an analogous sequence of reactions (Scheme 3).

Notes: Substituent Transformations on TriaziridinesSeveral novel triaziridines were prepared by substituent transformations starting from the known dialkyl-triaziridine-carboxylates 1a-c, with the aim to study the influence of the substitution pattern on the properties of the triaziridine ring. The dialkyl-triaziridines 2a-c were obtained by (t-BuO-)-mediated demethylation and decarboxylation and the dialkyl-triaziridine-methanols 4a-c by LiAlH4 reduction. Further reduction of the tosylates of 4a, b with LiAlH4 gave the methyl-dialkyl-triaziridines 3a, b. The dialkyl-triaziridines 2a, c could not be N-methylated directly with CH3I, but the anions 10a, c, obtained from 2a, c with CH3Li, yielded 3a, c. N-Methylation of 2a with (CH3)3OBF4 did not afford 3a but rather the methyl-triaziridinium salt 11. The dialkyl-triaziridine 2c has pKa 〉 14, its protonated species 〈 2. A concept that the electron pairs on the triaziridine N-atoms are more strongly localized than on amine N-atoms explains (a) that the dialkyl-triaziridine 2c is hardly basic, (b) that the LiAlH4 reductions of the esters 1 stop at the stage of the methanols 4, and (c) that the methanols 4a, b do not cleave like aminomethanols.

Notes: Oxidative Aryl-Aryl-Coupling of 6,6′,7,7′-Tetramethoxy-1,1′,2,2′,3,3′,4,4′-octahydro-1,1′-biisoquinoline DerivativesWe describe the synthesis of 2 by intramolecular oxidative coupling of 1, 1′-biisoquinoline derivatives 1 (Scheme 1). This heterocyclic system can be considered as a union of two apomorphine molecules and may thus exhibit dopaminergic activity. - The readily available tetrahydrobiisoquinoline 6 was methylated to 11 (Scheme 4) and reduced (with NaBH3CN) to rac-7 and (catalytically) to meso-7 (Scheme 3). Reduction of 11 with NaBH4 and of the biurethane rac-9 with LiAlH4/AlCl3 afforded meso- and rac-10, respectively (Scheme 4). Demethylation of 6, meso-10, meso- and rac-7 led to 12, meso-14, meso- and rac-13, respectively (Scheme 5). The latter two phenols were converted with chloroformic ester to the hexaethoxycarbonyl derivatives meso- and rac-15 and subsequently saponified to the biurethanes meso- and rac-16, respectively (Scheme 5). - In order to assure proximity of the two aromatic rings, the ethano-bridged derivatives meso- and rac-18 were prepared by condensing meso- and rac-7 with oxalic ester and reducing the oxalyl derivatives meso- and rac-17 with LiAlH4/AlCl3, respectively (Scheme 6). The 1H-NMR, spectra at different temperatures showed that rac-18 populated two conformers but rac-17 only one, all with C2-symmetry, and that meso-17 as well as meso-18 populated two enantiomeric conformers with C1-symmetry. Whereas both oxalyl derivatives 17 were fairly rigid due to the two amide groupings, the ethano derivatives 18 exhibited coalescence temperatures of -20 and 30°. - The intramolecular coupling of the two aromatic rings was successful under ‘non-phenolic oxidative’ conditions with the tetramethoxy derivatives 7, 10 and 18, the rac-isomers leading to the desired dibenzophenanthrolines, the meso-isomers, however, mostly to dienones (Scheme 9): With VOF3 and FSO3H in CF3COOH/CH2Cl2 rac-7 was converted to rac-19, rac-18 to rac-21 and rac-10 to a mixture of rac-20 and the dienone 23b of the morphinane type. Under the same conditions meso-10 was transformed to the dienone 23a of the morphinane type, whereas meso-18 yielded the dienone 24 of the neospirine type, both in lower yields. The analysis of the spectral data of the six coupling products offers evidence for their structures. With the demethylation of rac-20 and rac-21 to rac-25 and rac-26, respectively, the synthetic goal of the work was reached, but only in the rac-series (Scheme 10). - In the course of this work two cleavages of octahydro-1,1′-biisoquinolines at the C(1), C(1′)-bond were observed: (1) The biurethanes 9 and 16 in both the meso- and rac-series reacted with oxygen in CF3COOH solution to give the 3,4-dihydroisoquinolinium salts 27 and 28; the latter was deprotonated to the quinomethide 30 (Scheme 11). (2) Under the Clarke-Eschweiler reductive-methylation conditions meso- and rac-7 were cleaved to the tetrahydroisoquinoline derivative 32.

Notes: Reduction of 1,2-Bis[(Z)-(2-nitrophenyl)-NNO-azoxy]benzene1: Synthesis of Cyclotrisazobenzene ( = (5E,6aZ,11E,12aZ,17E,18aZ)-5,6,11,12,17,18-Hexaazatribenzo[aei][1,3,5,7,9,11]cyclododeca-hexaene)Na2S reduction of 1,2-bis[(Z)-(2-nitrophenyl)-NNO-azoxy]benzene (2) yielded 3 deoxygenated products: the (known) red 2,2′-((E,E)-1,2-phenylenbisazo)dianiline (3, 23%), the orange 2-[2-((E)-2-aminophenylazo)phenyl]-2H-benzotriazol (4, 55%) and the colorless 2,2′-(1,2-phenylene)di-2H-benzotriazol (5, 13%). The constitutions of 3-5 and of 6, the N-acetyl derivative of 4, were deduced from their 1H-NMR spectra (chemical shifts, couplings, and symmetry properties), and the configurations of 3, 4, and 6 at their N,N-double bonds are assumed to be the same as in 2. Oxidation of 3 with 2 mol-equiv. of Pb(OAc)4 afforded 5 (47%) and a novel, highly symmetrical macrocycle, called cyclotrisazobenzene (7, 24%). The constitution of 7 as a tribenzo-hexaaza[12]annulene and its (E)-configuration at the N,N-bonds was confirmed by X-ray analysis. The molecular symmetry expressed by the 1H-, 13C- and 15N-NMR spectra of 7 reveals a rapid torsional motion around the six N,C bonds. This implies that the N,N-double bonds in the cyclic 12π-electron system (or 24π-electron system if the benzene rings are included) of 7 are highly localized.