Thermische (E), (Z)-Isomerisierungen bei substituierten Propenylbenzolen

Thermal (E), (Z)-Isomerizations of Substituted Propenylbenzenes The thermal isomerizations of (E)- and (Z)-3,5-dimethyl-2-(1′-propenyl)phenol ((E)- and (Z)- 3 ), (E)- and (Z)-N-methyl-2-(1′-propenyl)anilin ((E)- and (Z)- 4 ), (E)- and (Z)-3,5-dimethyl-2-(1′-propenyl)anilin ((E)- and (Z)- 5 , (E)- and (Z)-2-(1′-propenyl)mesitylene ((E)- and (Z- 6 ), (E)- and (Z)-2-(1′-propenyl)mesitylene ((E)- and (Z)- 7 ), (E)- and (Z)-2-(1′-propenyl)toluene ((E)- and (Z)- 8 ), (E)- and (Z)-4-(1′-propenyl)toulene ((E)- and (Z)- 9 ) as well as of (E)- and (Z)-2-(2′-butenyl)-mesitylene ((E)- and (Z)- 10 ) in decane solution were studied (Scheme 2). Whereas the isomerization of the 2-propenylphenols (E)- and (Z)- 3 occurs already between 130 and 150° (cf. Table 1), the isomerization of the 2-propenylanilins 4 and 5 takes place only at temperatures between 220 and 250° (cf. Tables 2 and 3). The activation values and the experiments using N-deuterated 4 (cf. Scheme 4) show that 2-propenylphenols and -anilins isomerize via sigmatropic [1,5]-hydrogen-shifts. For the isomerization of the methyl-substituted propenylbenzenes temperatures > 360° are required (cf. Tables 4 and 5). The activation values of the isomerization of (E)- and (Z)- 6 and (E)- and (Z)- 9 are in accord with those of other (E), (Z)-isomerizations which occur via vibrationally excited singlet biradicals (cf. Table 7). Nevertheless, thermal isomerization of 2′-d-(Z)- 8 (cf. Scheme 6) demonstrates that during the reaction deuterium is partially transfered into the ortho-methyl group, i.e. 1,5-hydrogen-shifts must have participated in isomerization of (E)- and (Z)- 8 (cf. Scheme 8). Under the equilibrium conditions 2,4,6-trimethylindan ( 17 ) is formed slowly at 368° from (E)- and (Z)- 6 , very probably via a radical 1,4-hydrogen-shift (cf. Scheme 9). In a similar way 2-ethyl-4,6-dimethylindan ( 19 ; cf. Table 6) arises from (E)- and (Z)- 7 . Thermolysis of (E)- and (Z)- 10 in decane solution at 367° results in almost no (E),(Z)-isomerization. At prolonged heating 19 and 2,5,7-trimethyl-1,2,3,4-tetrahydronaphthalene ( 20 ) are formed; these two products arise very likely from an intermolecular radical process (cf. Scheme 10).     

Photochemische Reaktionen 111. Mitteilung [1] Zur Photochemie α, β-ungesättigter γ, δ-Epoxyester I: Singulett- versus Triplettreaktivität

On triplet excitation (E)- 2 isomerizes to (Z)- 2 and reacts by cleavage of the C(γ), O-bond to isomeric δ-ketoester compounds ( 3 and 4 ) and 2,5-dihydrofuran compounds ( 5 and 19 , s. Scheme 1). - On singulet excitation (E)- 2 gives mainly isomers formed by cleavage of the C(γ), C(δ)-bond ( 6–14 , s. Scheme 1). However, the products 3–5 of the triplet induced cleavage of the C(γ), O-bond are obtained in small amounts, too. The conversion of (E)- 2 to an intermediate ketonium-ylide b (s. Scheme 5) is proven by the isolation of its cyclization product 13 and of the acetals 16 and 17 , the products of solvent addition to b . - Excitation (λ = 254 nm) of the enol ether (E/Z)- 6 yields the isomeric α, β-unsaturated ε-ketoesters (E/Z)- 8 and 9 , which undergo photodeconjugation to give the isomeric γ, δ-unsaturated ε-ketoesters (E/Z)- 10 . - On treatment with BF₃O(C₂H₅)₂ (E)- 2 isomerizes by cleavage of the C(δ), O-bond to the γ-ketoester (E)- 20 (s. Scheme 2). Conversion of (Z)- 2 with FeCl₃ gives the isomeric furan compound 21 exclusively.     

Eine neue Aminoazirin-Reaktion. Bildung von 3,6-Dihydropyrazin-2(1H)-onen

A New Aminoazirine Reaction. Formation of 3,6-Dihydropyrazin-2(1H)-ones The reaction of 3-(dimethylamino)-2H-azirines 1 and 2-(trifluoromethyl)-1,3-oxazol-5(2H)-ones 5 in MeCN or THF at 50–80° leads to 5-(dimethylamino)-3,6-dihydropyrazin-2(1H)-ones 6 (Scheme 3). Reaction mechanisms for the formation of 6 are discussed: either the oxazolones 5 react as CH-acidic heterocycles with 1 (Scheme 4), or the azirines 1 undergo a nucleophilic attack onto the carbonyl group of 5 (Scheme 6). The reaction via intermediate formation of N-(trifluoroacetyl)dipeptide amide 8 (Scheme 5) is excluded.     

Bortrifluorid-katalysierte Umsetzungen von 3-Amino-2H-azirinen mit Aminosäure-estern und Aminen

Boron-Trifluoride-Catalyzed Reactions of 3-Amino-2H-azirines with Amino-acid Esters and Amines After activation by protonation or complexation with BF₃, 3-amino-2H-azirines 1 react with the amino group of α-amino-acid esters 3 to give 3,6-dihydro-5-aminopyrazin-2(1H)-ones 4 by ring enlargement (Scheme 2, Table 1). The configuration of 3 is retained in the products 4 . With unsymmetrically substituted 1 (R¹ ≠ R²), two diastereoisomers of 4 (cis and trans) are formed in a ratio of 1:1 to 2:1. With β-amino-acid esters 5 and 7 , only openchain α-amino-imidamides 6 and 8 , respectively, are formed, but none of the seven-membered heterocycle (Scheme 3). Primary amines also react with BF₃-complexed 1 to yield α-amino-imidamides of type 9 (Scheme 4, Table 2). Compound 9b is characterized chemically by its transformation into crystalline derivatives 10 and 12 with 4-nitrobenzoyl chloride and phenyl isothiocyanate, respectively (Scheme 5). The structure of 12 is established by X-ray crystallography. Mechanisms for the reaction of activated 1 with amino groups are proposed in Schemes 6 and 7.     

Introduction of Amino Alcohols in the Ring-Opening Reaction of 3-bromo-2,5-dimethylthiophene 1,1-dioxide. A short diastereoselective synthesis of substituted ‘tetrahydrobenzo[a]pyrrolizidines’ (= octahydro-1H-pyrrolo[2,1-a]isoindoles) using L-prolinol

Tetrahydrobenzo[a]pyrrolizidines (= octahydro-1H-pyrrolo[2,1-a]isoindoles) and tetrahydrobenzo[a]indo-lizidines, (= decahydropyrido[2,1-a]isoindoles) were prepared stereoselectively in four steps through an amineinduced ring-opening of 3-bromo-2,5-dimethylthiophene 1,1-dioxide ( 1 ) with L -prolinol ( 9 ), piperidine-2-methanol ( 10 ), and piperidine-2-ethanol ( 11 ), yielding the dienes (2S)-1-[(2E,4Z)-4-bromohexa-2,4-dienyl]pyrrolidine-2-methanol ( 12 ), 1-[(2E,4Z)-4-bromohexa-2,4-dienyl]piperidine-2-methanol ( 13 ), and 1-[(2E,4Z)-4-bromo-hexa-2,4-dienyl]piperidine-2-ethanol ( 14 ; Scheme2), which, after conversion into their α,β-unsaturated esters, cyclized in a TiCl₄-catalyzed intramolecular Diets-Alder reaction (Scheme3). A discussion on the mechanism of the ring opening reaction including semiempirical and ab initio calculations is also presented.     

Ringerweiterung von 1,2-Thiazol-3(2H)-on-1,1-dioxiden und 3-Amino-2H-azirinen zu 4H-1,2,5-Thiadiazocin-6-on-1,1-dioxiden

Ring Enlargement of 1,2-Thiazol-3(2H)-one-1,1-dioxides and 3-Amino-2H-azirines to 4H-1,2,5-Thiadiazocin-6-one-1,1-dioxides Reaction of 3-amino-2H-azirines 2 with the 1,1-dioxides 4 and 7 of 1,2-thiazol-3(2H)-ones and 1,2-thiazoli-din-3-ones, respectively, in i-PrOH at room temperature leads to 4H-1,2,5-thiadiazocin-6(5H)-one-1,1-dioxides 5 (Scheme 2, Table) and the corresponding 7,8-dihydro derivatives 8 (Scheme 4), respectively. The structure of some of the new 8-membered heterocycles as well as the structure of the minor by-product 6 (Scheme 3) have been established by X-ray crystallography (Chapt. 4). The proposed reaction mechanism for the ring expansion to 5 and 8 (Scheme 2) is in accordance with previously published results of reactions of 2 and NH-acidic heterocycles and is further supported by the results of the reaction of 4a and the (1-¹⁵N)-labelled aminoazirine 2a *.     

Reaktionen von 3-(Dimethylamino)-2H-azirinen mit 1,3-Benzoxazol-2(3H)-thion

Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Benzoxazole-2(3H)-thione The reaction of 3-(dimethylamino)-2H-azirines 2 with 1,3-benzoxazole-2(3H)-thione ( 5 ), which can be considered as NH-acidic heterocycle (pK_aca. 7.3), in MeCN at room temperature, leads to 3-(2-hydroxyphenyl)-2-thiohydantoins 6 and thiourea derivatives of type 7 (Scheme 2). A reaction mechanism for the formation of the products via the crucial zwitterionic intermediate A ′ is suggested. This intermediate was trapped by methylation with Mel and hydrolysis to give 9 (Scheme 4). Under normal reaction conditions, A ′ undergoes a ring opening to B which is hydrolyzed during workup to yield 6 or rearranges to give the thiourea 7. A reasonable intermediate of the latter transformation is the isothiocyanate E (Scheme 3) which also could be trapped by morpholine. In i-PrOH at 55–65° 2a and 5 react to yield a mixture of 6a , 2-(isopropylthio)-1,3-benzoxazole ( 12 ), and the thioamide 13 (Scheme 5). A mechanism for the surprising alkylation of 5 via the intermediate 2-amino-2-alkoxyaziridine F is proposed. Again via an aziridine, e.g. H ( Scheme 6 ), the formation of 13 can be explained.     

Reaktion von 3-(Dimethylamino)-2H-azirinen mit 1,3-Thiazolidin-2-thion

Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Thiazolidine-2-thione Reaction of 3-(dimethylamino)-2H-azirines 1 and 1,3-thiazolidine-2-thione ( 6 ) in MeCN at room temperature leads to a mixture of perhydroimidazo[4,3-b]thiazole-5-thiones 7 and N-[1-(4,5-dihydro-1,3-thiazol-2-yl)alkyl]-N′,N′-dimethylthioureas 8 (Scheme 2), whereas, in i-PrOH at ca. 60°, 8 is the only product (Scheme 4). It has been shown that, in polar solvents or under Me₂NH catalysis, the primarily formed 7 isomerizes to 8 (Scheme 4). The hydrolysis of 7 and 8 leads to the same 2-thiohydantoine 9 (Scheme 3 and 5). The structure of 7a, 8c , and 9b has been established by X-ray crystallography (Chapt. 4). Reaction mechanisms for the formation and the hydrolysis of 7 and 8 are suggested.     

Zur Imidazolbildung aus 2H-Azirinen bzw. Vinylaziden und Nitrilen unter Säurekatalyse

Acid-Catalysed Formation of Imidazoles from 2H-Azirines or Vinylazides and Nitriles The reaction of 2H-azirines with nitriles in the presence of boron trifluoride etherate to yield the corresponding imidazoles is described. 2,3-Diphenyl-2H-azirine ( 10 ) gives 2-substituted 4,5-diphenyl imidazoles in moderate bis good yields (see Table 1). The reaction of 10 with acrylonitrile only leads to the formation of 4,5-diphenyl-2-vinylimidazole ( 17 ). No products resulting from an addition to the C,C double bond are observed. 2H-Azirine 10 and ethyl cyanoacetate yield the expected imidazole 18 (30%) but also 2-cyanomethyl-4,5-diphenyloxazole ( 20 ; 7%) (see Scheme 4). The yield of imidazole formation mainly depends on the substituents in position 2 of the 2H-azirines (see Scheme 6), a change of the substitutents in position 3 having only little influence. The best yields are observed with a phenyl group at C(2) of the 2H-azirines. These observations are in agreement with the occurrence of 1-azaallyl cations formed by ring opening of the 2H-azirines linked to the Lewis acid (boron trifluoride). Similar results are obtained with the corresponding vinyl azides with the exception of 1-azido-1-phenylethylene ( 28 ). Whereas the corresponding 3-phenyl-2H-azirine ( 24 ) gives 2,4-diphenylimidazole ( 33 ; Scheme 6) in the presence of benzonitrile and boron trifluoride etherate, the azide 28 yields only acetanilide (86%). In the presence of triethyloxonium tetrafluoroborate 2H-azirines and benzonitrile react to yield the corresponding 1-ethylimidazoles (see Scheme 9). This again demonstrates that 1-azaallyl cations must be intermediates which react with the nitrile presumably in a Ritter type reaction. ¹³C-NMR. spectra of 2H-azirines are also reported (Table 2).     

Herstellung neuer polycyclischer Verbindungen durch intramolekulare Diels-Alder-Reaktionen von Cyclohexa-2,4-dien-1-on-Abkömmlingen

Synthesis of new polycyclic compounds by means of intramolecular Diels-Alder reactions of cyclohexa-2,4-dien-1-one derivatives Thermal rearrangement of mesityl penta-2,4-dienyl ether ( 1 ), consisting of the isomers E (93%) and Z (7%), furnished, besides mesitol, the two mesityl penta-1,3-dienyl ethers 2 (24%) and 3 (3%), and the two tricyclic ketones 4 (4,5%) and 5 (12,5%) (Scheme 1). A probable mechanism for this formation of 2 involves a [1,5]-hydrogen shift in (Z)- 1 . Isomerisation of (E)- 1 to (Z)- 1 at 145° occurs via reversible sigmatropic [3,3]- and [5,5]-rearrangements of (E)- 1 to the cyclohexadienones 38 and 39 respectively (see Chapter A p. 1710, and Scheme 15). Formation of 3 from either (Z)- 1 or 2 is rationalized by a series of pericyclic reactions as outlined in Chapter A and Scheme 16. The tricyclic ketones 4 and 5 are undoubtedly formed by internal Diels-Alder reactions of the 6-pentadienyl-cyclohexa-2,4-dien-1-one 6 (Scheme 2). In fact, at 80° 6 is converted into 4 (5%) and 5 (35%). At 80° the cyclohexadienone derivative 7 furnished the corresponding tricyclic ketones 8 (15%) and 9 (44%) (Scheme 2). 5 and 9 contain a homotwistane skeleton. 8 and 9 are easily prepared by reaction of sodium 2,6-dimethylphenolate with 3-methyl-penta-2,4-dienyl bromide at ambient temperature, followed by heating, and finally separation by cristallization and chromatography. The cyclohexadienones 6 and 7 have mainly (E)-configuration. Here too (E) → (Z) isomerization is a prerequisite for the internal Diels-Alder reaction, and this partly takes place intramolecularly through reversible Claisen and Cope rearrangements (Scheme 17). On the other hand, experiments in the presence of 3,5-d₂-mesitol have shown (Table 1) that intermolecular reactions, involving radicals and/or ions, are also operating (see Chapter B , p. 1712). Two different modi (I and II) exist for intramolecular Diels-Alder reactions (Scheme 18). Whereas only modus I is observed in the cyclization of 5-alkenyl-cyclohexa-l,3-dienes, in that of (2)-cyclohexadienones 6 and 7 (Scheme 2) both modi are operating. Only in modus 11-type transitions is the butadienyl conjugation of the side chain retained, so that modus 11-type addition is preferred (Chapter C p. 1716). Analogously to the synthesis of the tricyclic ketones 4 , 5 , 8 and 9 , the tricyclic ketone 15 (Scheme 4) and the tetracyclic ketone 11 (Scheme 3) are prepared from mesitol, pentenyl bromide and cycloheptadienyl bromide, respectively. From the polycyclic ketones derivatives such as the alcohols 16 , 17 , 18 , 19 , 23 , 24 and 25 (Schemes 9 and 11), policyclic ethers 20 , 21 , 22 and 26 (Scheme 10), epoxides 30 , 32 (Scheme 13), diketones 31 , 33 (Scheme 13) and ether-alcohols 35 and 36 (Scheme 14) have been prepared. Most of these conversions show high stereoselectivity.     

Aromatische sigmatropische Wasserstoffverschiebungen in 2-Vinyl- und 2-Allylphenolen

Aromatic Sigmatropic Hydrogen-Shifts in 2-Vinyl- and 2-Allyl-phenols It is shown by deuterium labeling experiments that 2-vinylphenols, on heating at 142,5°, undergo aromatic [1,5]-H-shifts whereby o-quinone methides are formed as intermediates (Scheme 7). Thus, heating of 2-isopropenylphenol ( 6 ) in a D₂O/dioxane mixture leads to a rapid deuterium incorporation into the methylidene group of the isopropenyl moiety (Table 1) whereas its methyl group shows only a slow uptake of deuterium. The latter exchange process can be attributed to intermolecular reactions (Scheme 8). The quinone methide intermediates (e.g. 26 , Scheme 8) can be regarded as vinyl homologues of alkyl ketones. Therefore, 26 can exchange hydrogen in both methyl groups by an acid- and base-catalysed mechanism. Indeed, when 6 is heated in D₂O/pyridine or D₂O/CH₃COOD/dioxane, an almost statistical incorporation of deuterium into the methylidene and the methyl group of the isopropenyl moiety is observed (Table 3). As a consequence of thermally induced [1,5]-H-shifts, 2-(1′-propenyl)-phenols undergo rapid (E,Z) isomerization with first order kinetics on heating above 140° in decane solution. Activation parameters are given in Table 4. The observed primary +++++ H/D isotope effect of 3.3 in the (E,Z) isomerization of phenol 8 is in +++ment with intramolecular H/D-shifts in the rate determing step (Scheme 9 +++ Table 5). As expected aromatic sigmatropic [1,5]-H-shifts in 2-(1′-propenyl)-+++ are much faster than aromatic homosigmatropic [1,5]-H-shifts in 2-(2′-+++++)phenols (Scheme 1 and Table 6). The structurally comparable phenols +++ (Z)- 10 and (E)/(Z)- 14 (Scheme 3) show k([1,5])/k(homo-[1,5]) ≈ 2300 at ++++

1 A more detailed discussion in English is given in [1].

.     

Photochemische Cycloadditionen von 3-Phenyl-2H-azirinen mit Triphenyl-vinylphosphoniumbromid. 36. Mitteilung über Photoreaktionen

On irradiation in acetonitrile 3-phenyl-2H-azirines of type 1 react with triphenyl vinyl phosphonium bromide to form in approximative 50% yield 2H-indoles of type 4 (Scheme 1). In analogy to other photochemical reactions with 2H-azirines [2] [3] it is assumed that the photochemically generated dipoles 2 react with the triphenyl vinyl phosphonium salt (Scheme 1). The conversion of 1 to 4 represents a new synthesis for 2H-pyrroles.     

Über die «aus dem Ring»-Claisen-Umlagerung von Naphthalinderivaten

When a mixture of (E)- and (Z)-1-propenylnaphth-2-yl-allylether ((E/Z)- 5 ) is heated to 182° only the (E)-isomer rearranges to give the ‘out-of-ring’ product (E/Z)- 16 , (Z)- 5 remains unchanged. At higher temperature (Z)- 5 yields 2-methyl-naphtho[2,1-b]furane ( 15 ) as the main product. The mixture of β-chloro-allyl derivatives (E/Z)- 6 behaves in a similar way. These findings led us to suspect that the ‘out-of-ring’ products 16 and 18 are formed by direct [1, 5s] allyl migration from the starting ethers (E)- 5 and (E)- 6 . Kinetic' measurements made on (E)- and (Z)- 5 and the independently synthesized (E)- and (Z)-1-allyl-1-propenyl-1 H-naphthalen-2-ones ((E)- and (Z)- 17 ) show however, that the ethers (E)- 5 and (E)- 6 undergo a double [3s, 3s] rearrangement (i.e. Claisen followed by Cope rearrangement) and hydrogen migration to yield the ‘out-of-ring’ products (E/Z)- 16 and (E/Z)- 18 (Scheme 9). In the (Z)-series steric factors prevent the intermediate naphthalenones (Z)- 17 and (Z)-19 from undergoing the Cope rearrangement and instead, at higher temperature, cleavage of the allyl group occurs (Scheme 11). The isopropenyl derivative 7 behaves in a similar way (Scheme 5). Rearrangement of (E/Z)-1-propenylnaphth-2-yl benzyl ether ( 8 ) requires a higher temperature (214°). The nature of the products obtained (Scheme 4) makes the occurrence of a direct sigmatropic [1,5s] shift of the benzyl group very unprobable. In the case of (E/Z)-2-propenylnaphth-1-yl allyl ether ( 10 ) both isomers rearrange to yield the ‘out-of-ring’ product 30 and the para-Claisen product 32 (Scheme 7). This experiment also provides evidence against a sigmatropic [1,5s] shift of the allyl group. The same conclusion can be drawn from the thermal behaviour of (E/Z)-2-propenylphenyl allyl ether (11) and 6-t-butyl-2-propenylphenyl allyl ether ( 12 ) where only 11 yields traces of the ‘out-of-ring’ product 35 (Scheme 8). Up to this date there is no evidence whatsoever for the existence of a sigmatropic [1,5s] migration of an allyl group from oxygen to carbon. Thermal rearrangement of (E/Z)-1-propenylnaphth-2-yl propargyl ether ( 9 ) yields only (E/Z)-1-propenyl-benz[e]indan-2-one ( 27 ) (and its secondary product 28 ). The mechanism for this reaction is given in Scheme 12. Treatment of a mixture of (E/Z)- 18 with base yields the (Z)-cyclisation product 2,4-dimethylnaphth[2,1-b]oxepine ( 43 ) (Scheme 13).     

Unexpected Thermal Transformation of Aryl 3‐Arylprop‐2‐ynoates: Formation of 3‐(Diarylmethylidene)‐2,3‐dihydrofuran‐2‐ones

A number of aryl 3‐arylprop‐2‐ynoates 3 has been prepared (cf. Table 1 and Schemes 3 – 5). In contrast to aryl prop‐2‐ynoates and but‐2‐ynoates, 3‐arylprop‐2‐ynoates 3 (with the exception of 3b ) do not undergo, by flash vacuum pyrolysis (FVP), rearrangement to corresponding cyclohepta[b]furan‐2(2H)‐ones 2 (cf. Schemes 1 and 2). On melting, however, or in solution at temperatures >150°, the compounds 3 are converted stereospecifically to the dimers 3‐[(Z)‐diarylmethylidene]‐2,3‐dihydrofuran‐2‐ones (Z)‐ 11 and the cyclic anhydrides 12 of 1,4‐diarylnaphthalene‐2,3‐dicarboxylic acids, which also represent dimers of 3 , formed by loss of one molecule of the corresponding phenol from the aryloxy part (cf. Scheme 6). Small amounts of diaryl naphthalene‐2,3‐dicarboxylates 13 accompanied the product types (Z)‐ 11 and 12 , when the thermal transformation of 3 was performed in the molten state or at high concentration of 3 in solution (cf. Tables 2 and 4). The structure of the dihydrofuranone (Z)‐ 11c was established by an X‐ray crystal‐structure analysis (Fig. 1). The structures of the dihydrofuranones 11 and the cyclic anhydrides 12 indicate that the 3‐arylprop‐2‐ynoates 3 , on heating, must undergo an aryl O→C(3) migration leading to a reactive intermediate, which attacks a second molecule of 3 , finally under formation of (Z)‐ 11 or 12 . Formation of the diaryl dicarboxylates 13 , on the other hand, are the result of the well‐known thermal Diels‐Alder‐type dimerization of 3 without rearrangement (cf. Scheme 7). At low concentration of 3 in decalin, the decrease of 3 follows up to ca. 20% conversion first‐order kinetics (cf. Table 5), which is in agreement with a monomolecular rearrangement of 3 . Moreover, heating the highly reactive 2,4,6‐trimethylphenyl 3‐(4‐nitrophenyl)prop‐2‐ynonate ( 3f ) in the presence of a twofold molar amount of the much less reactive phenyl 3‐(4‐nitrophenyl)prop‐2‐ynonate ( 3g ) led, beside (Z)‐ 11f , to the cross products (Z)‐ 11fg , and, due to subsequent thermal isomerization, (E)‐ 11fg (cf. Scheme 10), the structures of which indicated that they were composed, as expected, of rearranged 3f and structurally unaltered 3g . Finally, thermal transposition of [¹⁷O]‐ 3i with the ¹⁷O‐label at the aryloxy group gave (Z)‐ and (E)‐[¹⁷O₂]‐ 11i with the ¹⁷O‐label of rearranged [¹⁷O]‐ 3i specifically at the oxo group of the two isomeric dihydrofuranones (cf. Scheme 8), indicating a highly ordered cyclic transition state of the aryl O→C(3) migration (cf. Scheme 9).     

4-Amino-1,5-dihydro-2H-pyrrol-2-one aus Bortrifluorid-katalysierten Umsetzungen von 3-Amino-2H-azirinen mit Carbonsäure-Derivaten

4-Amino-1,5-dihydro-2H-pyrrol-2-ones from Boron Trifluoride Catalyzed Reactions of 3-Amino-2H-azirines with Carboxylic Acid Derivatives Reaction of 3-amino-2H-azirines 1 with ethyl 2-nitroacetate ( 6a ) in refluxing MeCN affords 4-amino-1,5-dihydro-2H-pyrrol-2-ones 7 and 3,6-diamino-2,5-dihydropyrazines 8 , the dimerization product of 1 (Scheme 2). Thus, 6a reacts with 1 as a CH-acidic compound by C? C bond formation via C-nucleophilic attack of deprotonated 6a onto the amidinium-C-atom of protonated 1 (Scheme 5). The scope of this reaction seems to be rather limited as 1 and 2-substituted 2-nitroacetates do not give any products besides the azirine dimer 8 (see Table 1). Sodium enolates of carboxylic esters and carboxamides 11 react with 1 under BF₃ catalysis to give 4-amino-1,5-dihydro-2H-pyrrol-2-ones 12 in 50–80% yield (Scheme 3, Table 2). In an analogous reaction, 3-amino-2H-pyrrole 13 is formed from 1c and the Li-enolate of acetophenone (Scheme 4). A reaction mechanism for the ring enlargement of 1 involving BF₃ catalysis is proposed in Scheme 6.     

Umsetzung von 3-Amino-2H-azirinen mit Salicylohydrazid

Reaction of 3-Amino-2H-azirines with Salicylohydrazide 3-Amino-2H-azirines 1a–g react with salicylohydrazide ( 7 ) in MeCN at 80° to give 2H, 5H-1,2,4-triazines 10 , 1,3,4-oxadiazoles 12 and, in the case of 1d , 1,2,4-triazin-6-one 11a (Scheme 3). The precursor of these heterocycles, the amidrazone of type 9 , except for 9c and 9g , which could not be isolated, has been found as the main product after reaction of 1 and 7 in MeCN at room temperature. 3-(N-Methyl-N-phenylamino)-2-phenyl-2H-azirin ( 1g ) reacts with 7 to give mainly the aromatic triazines 15b₁ and 15b₂ . In this case, two unexpected by-products, 16 and salicylamide ( 17 ), occurred, probably by disproportionation of a 1:1 adduct from 1g and 7 (Scheme 8). Oxidation of 10f with DDQ leads to the triazine 15a . The structure of 10c, 11a, 12c, 13 (by-product in the reaction of 1b and 7 ), the N′-phenylureido derivative 14 of 9d (Scheme 4) as well as 15b₂ has been established by X-ray crystallography. The ratio of 10/12 as a function of substitution pattern in 1 and solvent has been investigated (Tables 1, 3, 4, and 7). A mechanism for the formation of 10 and 12 is proposed in Scheme 7.     

Studies on the Stereochemistry of 2-(Nitromethylidene)-Heterocycles

The ¹H-NMR spectra of 2-(nitromethylidene)pyrrolidine ( 7 ), 1-methyl-2-(nitromethylidene)imidazolidind ( 10 ) and 3-(nitromethylidene)tetrahydrothiazine ( 11 ) in CDCl₃ and (CD₃)₂SO indicate that these compounds have the intramolecularly H-bonded structures (Z)- 7 , (E)- 10 and (Z)- 11 while the N-methyl derivative 8 of 7 is (E)-configurated in both solvents. 1-Benzylamino-1-(methyltio)-2-nitroehtylene ( 13 ), an acylic model, has the H-bonded configuration (E)- 13 in CDCl₃ and in (CD₃)₂SO. 2-(Nitromethylidene)thiazolidine ( 3 ) has the (E)-configuration in CDCl₃ but exists in (CD₃)₂SO as a mixture of (Z)- and (E)-isomers with the former predominating. Both species are detected to varying proportions in a mixture of the two solvents. ¹⁵N-NMR spectroscopy of 3 ruled out unambiguously the nitronic acid structure 6 and the nitromethyleimine structure 5 . The N-methyl derivative 4 of 3 is (Z)-configurated in (CD₃)₂SO. Comparison of the olefinic proton shifts of (Z)- 3 and (Z)- 4 with those of analogues and also of 1,1-bis(methylti)-2-nitroethylene ( 12 ) shows decreased conjugation of the lone pair of electrons of the ring N-atom in (Z)- 3 and (Z)- 4 . This is also supported by ¹³C-NMR studies. Plausible explanations for the phenomenon are offered by postulating that the ring N-atoms are pyramidal in (Z)- 3 and (Z)- 4 and planar in other cases or, alternatively, that the conjugated nitroenamine system gets twisted due to steric interaction between the NO₂-group and the ring S-atom. Single-crystal X-ray studies of 3 and 8 show that the former exists in the (Z)-configuration and the latter in (E)-configuration; the ring N-atom in the former has slightly more pyramidal character than in the latter.     

Dipolare (1:1)-Addukte aus der Reaktion von 3-Amino-2H-azirinen mit 1,3,4-Oxadiazol- und 1,3,4-Thiadiazol-2(3H)-onen

Dipolar 1:1 Adducts from the Reaction of 3-Amino-2H-azirines with 1,3,4-Oxadiazol- and 1,3,4-Thiadiazol-2(3H)-ones 3-Amino-2H-azirines 1 react with 5-(trifluoromethyl)-1,3,4-oxadiazol-2(3H)-one ( 2 ) as well as with different 5-substituted 1,3,4-thiadiazol-2(3H)-ones ( 5a–e ) in 2-propanol at room temperature to give dipolar 1:1 adducts of type 3 and 6 , respectively, in reasonable-to-good yields (Schemes 3 and 6, Tab. 1 and 2). The structure of two of these dipolar adducts, 6a and 6e , which are formally donor-acceptor-stabilized azomethin imines, have been elucidated by X-ray crystallography (Figs. 1-4). In the reaction of 2 and sterically crowded 3-amino-2H-azirines 1c–e with a 2-propyl and 2-propenyl substituent, respectively, at C(2), a 4,5-dihydro-1,2,4-triazin-3(2H)-one of type 4 is formed as minor product (Scheme 3 and Table 1). Independent syntheses of these products proved the structure of 4 . Several reaction mechanisms for the formation of compounds 3 and 4 are discussed, the most likely ones are described in Scheme 4: reaction of 2 as an NH-acidic compound leads, via a bicyclic zwitterion of type A , to 3 as well as to 4 . In the latter reaction, a ring-expanded intermediate B is most probable.     

Reaktion von Phenyldiazomethan mit 1,3-Thiazol-5(4H)-thionen: Basenkatalysierte Ring-Öffnung des Primäradduktes

Reaction of Phenyldiazomethane with 1,3-Thiazole-5(4H)-thiones: Base-Catalyzed Ring Opening of the Primary Adduct Reaction of 1,3-thiazole-5(4H)-thiones 1 and phenyldiazomethane ( 2a ) in toluene at room temperature yields the thiiranes trans- and cis-1,4-dithia-6-azaspiro[2.4]hept-5-enes (trans- and cis- 4 ; Scheme 2). With Ph₃P in THF at 70°, these thiiranes are transformed stereospecifically into (E)- and (Z)-5-benzylidene-4,5-dihydro-1,3-thiazoles 5 , respectively. In the presence of DBU, 1 and 2a react to give 1,3,4-thiadiazole derivatives 6 or 7 via base-catalyzed ring opening of the primary cycloadduct (Scheme 3). In the case of 2-(alkylthio)-substituted 1,3-thiazole-5(4H)-thiones 1c and 1d , this ring opening proceeds by elimination of the corresponding alkylthiolate, yielding isothiocyanate 7 . The structures of (Z)- 5c and 6b have been established by X-ray crystallography.     

Chiral [2H]-Labelled Methylene Groups in Trienoic- and Dienoic Fatty Acids: A Facile Approach via Asymmetric Epoxidation of [2H] Allyl Alcohols

Chiral [²H] -labelled methylene groups flanked by two double bonds within (poly)unsaturated fatty acids are readily available from trans-2,3-epoxy[2,3-²H₂] alk-4-yn-l-ols, obtained in their turn by asymmetric epoxidation of the corresponding (E)-[2,3-²H₂] alk-2-en-4-yn-l-ols (see Scheme 3). The procedure is exemplified for (8S,3Z,6Z,9Z)-[7,8-²H₂] trideca-3,6,9-trienoic acid ((8S)- 11 ) and (8R)- 11 (Scheme 4) as well as for (5S,3Z,6Z)-[4,5^?2H₂]deca-3,6-dienoic acid ((5S)- 13 ) and (5R)- 13 (Scheme 5).