Some Unusual Products from the Thermal Reaction of Azulenes with Dimethyl Acetylenedicarboxylate

The thermal reaction of azulene-1-carbaldehydes 5 and 6 with excess dimethyl acetylenedicarboxylate (ADM) in decalin leads mainly to the formation of (1 + 1) and (1 + 2) adducts arising from the addition of ADM at the seven-membered ring of the azulenes (cf. Schemes 2 and 4). The (1 + 2) adducts are formed in a homo-Diels-Alder reaction of ADM and isomeric tricyclic carbaldehydes which are derived from the primary tricyclic carbaldehydes by reversible [1s5s]-C shifts (cf. Schemes 3 and 5). The thus formed pentacyclic carbaldehydes seem to undergo deep-seated skeletal rearrangements (cf. Scheme 7) which result finally in the formation of the formyl-tetrahydrocyclopenta[bc]acenaphthylene-tetraesters 12 and 19 , respectively. In other cases, e.g., azulene-1-carbaldehydes 7 and 8 (cf. Scheme 8), the thermal reaction with excess ADM furnishes only the already known tetracycfic (1 + 2) adducts of type anti- 26 to ‘anti’- 29 . The thermal reaction of 1,3,4,8-tetramethylazulene ( 9 ) with excess ADM in decalin resulted in the formation of two (1 + 2) and one (1 + 3) adduct in low yields (cf. Scheme 9). The latter turned out to be the 2,6-bridged barrelene derivative 32 . There are structural evidences that 32 is formed by similar pathways as the formyl-tetrahydrocyclopenta[bc]acenaphthylene-tetraesters (cf. Schemes 7 and 11). [²H₃]Me-Labelling experiments are in agreement with the proposed mechanisms (cf. Scheme 13).     

Thermal and Ru-catalyzed Reactions of Styryl-Substituted Azulenes with Dimethyl Acetylenedicarboxylate

The thermal reaction of 1-[(E)-styrl]azulenes with dimethyl acetylenedicarboxylate (ADM) in decalin at 190–200° does not lead to the formation fo the corresponding heptalene-1,2-dicarboxylates (Scheme 2). Main products are the corresponding azulene-1,2-dicarboxylates (see 4 and 9 ), accompanied by the benzanellated azulenes trans- 10a and trans- 11 , respectively. The latter compounds are formed by a Diels-Alder reaction of the starting azulenes and ADM, followed by an ene reaction with ADM (cf. Scheme 3). The [RuH₂(PPh₃)₄]-catalyzed reaction of 4,6,8-trimethyl-1-[(E)-4-R-styryl]azulenes (R=H, MeO, Cl; Scheme 4) with ADM in MeCN at 110° yields again the azulene-1,2-dicarboxylates as main products. However, in this case, the corresponding heptalene-1,2-dicarboxylates are also formed in small amounts (3–5%; Scheme 4). The benzanellated azulenes trans- 10a and trans- 10b are also found in small amounts (2–3%) in the reaction mixture. ADM Addition products at C(3) of the azulene ring as well as at C(2) of the styryl moiety are also observed in minor amounts (1–3%). Similar results are obtained in the [RuH₂(PPh₃)₄]-catalyzed reaction of 3-[(E)-styryl]guaiazulene ((E)- 8 ; Scheme 5) with ADM in MeCN. However, in this case, no heptalene formation is observed, and the amount of the ADM-addition products at C(2) of the styryl group is remarkably increased (29%). That the substitutent pattern at the seven-membered ring of (E)- 8 is not responsible for the failure of heptalene formation is demonstrated by the Ru-catalyzed reaction of 7-isopropyl-4-methyl-1-[(E)-styryl]azulene ((E)- 23 ; Scheme 11) with ADM in MeCN, yielding the corresponding heptalene-1,2-dicarboxylate (E)- 26 (10%). Again, the main product is the corresponding azulene-1,2-dicarboxylate 25 (20%). Reaction of 4,6,8-trimethyl-2-[(E)-styryl]azulene ((E)- 27 ; Scheme 12) and ADM yields the heptalene-dicarboxylates (E)- 30A / B , purely thermally in decalin (28%) as well as Ru-catalyzed in MeCN (40%). Whereas only small amounts of the azulene-1,2-dicarboxylate 8 (1 and 5%, respectively) are formed, the corresponding benzanellated azulene trans- 29 ist found to be the second main product (21 and 10%, respectively) under both reaction conditions. The thermal reaction yields also the benzanellated azulene 28 which is not found in the catalyzed variant of the reaction. Heptalene-1,2-dicarboxylates are also formed from 4-[(E)-styryl]azulenes (e.g. (E)- 33 and (E)- 34 ; Scheme 14) and ADM at 180–190° in decalin and at 110° in MeCN by [RuH₂(PPh₃)₄] catalysis. The yields (30%) are much better in the catalyzed reaction. The formation of by-products (e.g. 39–41 ; Scheme 14) in small amounts (0.5–5%) in the Ru-catalyzed reactions allows to understand better the reactivity of zwitterions (e.g. 42 ) and their triyclic follow-up products (e.g. 43 ) built from azulenes and ADM (cf. Scheme 15).     

New Results in the Synthesis of Styrylazulene Derivatives: Application of the ‘Anil synthesis’ to the preparation of azulenes substituted with styryl groups at the seven-membered ring

The synthesis of 4,6,8-trimethyl-1-[(E)-4-R-styryl]azulenes 5 (R=H, MeO, Cl) has been performed by Wittig reaction of 4,6,8-trimethylazulene-1-carbaldehyde ( 1 ) and the corresponding 4-(R-benzyl)(triphenyl)phosphonium chlorides 4 in the presence of EtONa/EtOH in boiling toluene (see Table 1). In the same way, guaiazulene-3-carbaldehyde ( 2 ) as well as dihydrolactaroviolin ( 3 ) yielded with 4a the corresponding styrylazulenes 6 and 7 , respectively (see Table 1). It has been found that 1 and 4b yield, in competition to the Wittig reaction, alkylation products, namely 8 and 9 , respectively (cf. Scheme 1). The reaction of 4,6,8-trimethylazulene ( 10 ) with 4b in toluene showed that azulenes can, indeed, be easily alkylated with the phosphonium salt 4b . 4,6,8-Trimethylazulene-2-carbaldehyde ( 12 ) has been synthesized from the corresponding carboxylate 15 by a reduction (LiAlH₄) and dehydrogenation (MnO₂) sequence (see Scheme 2). The Swern oxidation of the intermediate 2-(hydroxymethyl)azulene 16 yielded only 1,3-dichloroazulene derivatives (cf. Scheme 2). The Wittig reaction of 12 with 4a and 4b in the presence of EtONa/EtOH in toluene yielded the expected 2-styryl derivatives 19a and 19b , respectively (see Scheme 3). Again, the yield of 19b was reduced by a competing alkylation reaction of 19b with 4b which led to the formation of the 1-benzylated product 20 (see Scheme 3). The ‘anil synthesis’ of guaiazulene ( 21 ) and the 4-R-benzanils 22 (R=H, MeO, Cl, Me₂N) proceeded smoothyl under standard conditions (powered KOH in DMF) to yield the corresponding 4-[(E)-styryl]azulene derivatives 23 (see Table 4). In minor amounts, bis(azulen-4-yl) compounds of type 24 and 25 were also formed (see Table 4). The ‘anil reaction’ of 21 and 4-NO₂C₆H₄CH=NC₆H₅ ( 22e ) in DMF yielded no corresponding styrylazulene derivative 23e . Instead, (E)-1,2-bis(7-isopropyl-1-methylazulen-4-yl)ethene ( 27 ) was formed (see Scheme 4). The reaction of 4,6,8-trimethylazulene ( 10 ) and benzanil ( 22a ) in the presence of KOH in DMF yielded the benzanil adducts 28 to 31 (cf. Scheme 5). Their direct base-catalyzed transformation into the corresponding styryl-substituted azulenes could not be realized (cf. Scheme 6). However, the transformation succeeded smoothly with KOH in boiling EtOH after N-methylation (cf. Scheme 6).     

Formation of 6,10‐Diphenyl‐Substituted Heptalene‐4,5‐dicarboxylates

It is shown that 4,8‐diphenylazulene ( 1 ) can be easily prepared from azulene by two consecutive phenylation reactions with PhLi, followed by dehydrogenation with chloranil. Similarly, a Me group can subsequently be introduced with MeLi at C(6) of 1 (Scheme 2). This methylation led not only to the expected main product, azulene 2 , but also to small amounts of product 3 , the structure of which has been determined by X‐ray crystal‐structure analysis (cf. Fig. 1). As expected, the latter product reacts with chloranil at 40° in Et₂O to give 2 in quantitative yields. Vilsmeier formylation of 1 and 2 led to the formation of the corresponding azulene‐1‐carbaldehydes 4 and 5 . Reduction of 4 and 5 with NaBH₄/BF₃ ? OEt₂ in diglyme/Et₂O 1 : 1 and BF₃ ? OEt₂, gave the 1‐methylazulenes 6 and 7 , respectively. In the same way was azulene 9 available from 6 via Vilsmeier formylation, followed by reduction of azulene‐1‐carbaldehyde 8 (Scheme 3). The thermal reactions of azulenes 1, 6 , and 7 with excess dimethyl acetylenedicarboxylate (ADM) in MeCN at 100° during 72 h afforded the corresponding heptalene‐4,5‐dicarboxylates 11, 12 , and 13 , respectively (Scheme 4). On the other hand, the highly substituted azulene 9 gave hardly any heptalene‐4,5‐dicarboxylate.     

Ru-Catalyzed Heptalene Formation from Azulenes and Dimethyl Acetylenedicarboxylate

It is shown that azulenes react with dimethyl acetylenedicarboxylate (ADM) in solvents such as toluene, dioxan, or MeCN in the presence of 2 mol-% [RuH₂(PPh₃)₄] already at temperatures as low as 100° and lead to the formation of the corresponding heptalene-1,2-dicarboxylates in excellent yields (Tables 1 and 2). The Ru-catalyzed reaction of ADM with 1-(tert-butyl)-4,6,8-trimethylazulene ( 31 ) takes place even at room temperature, yielding the primary tricyclic addition product 32 and its thermal retro-Diels-Alder product dimethyl 4,6,8-trimethylazulene-1,2-dicarboxylate ( 21 ; Scheme 4). At 100° in MeCN, 32 yields 90% of 21 and only 10% of the corresponding heptalene. These observations demonstrate that [RuH₂(PPh₃)₄] catalyzes the first step of the thermal formation of heptalenes from azulenes and ADM which occurs in apolar solvents such as tetralin or decalin at temperatures > 180° (cf. Scheme 1).     

Thermal Reaction of Azulene-1-carbaldehydes with Dimethyl Acetylenedicarboxylate

Azulene-1-carbaldehydes which have Me substituents at C(3) and C(8) and no substituent at C(6) react with excess dimethyl acetylenedicarboxylate (ADM) in decalin at 200° to yield exclusively the Diels-Alder adduct at the seven-membered ring (cf. Scheme 3). The corresponding 1-carboxylates behave similarly (Scheme 4). Azulene-1-carbaldehydes which possess no Me substituent at C(8) (e.g. 11 , 12 in Scheme 2) gave no defined products when heated with ADM in decalin. On the other hand, Me substitutents at C(2) may also assist the thermal addition of ADM at the seven-membered ring of azulene-1-carbaldehydes (Scheme 6). However, in these cases the primary tricyclic adducts react with a second molecule of ADM to yield corresponding tetracyclic compounds. The new tricyclic aldehydes 16 and 17 which were obtained in up to 50% yield (Scheme 3) could quantitatively be decarbonylated with [RhCl(PPh₃)₃] in toluene at 140° to yield a thermally equilibrated mixture of four tricycles (Scheme 8). It was found that the thermal isomerization of these tricycles occur at temperatures as low as 0° and that at temperatures > 40° the thermal equilibrium between the four tricycles is rapidly established via [1,5]-C shifts. The establishment of the equilibrium makes the existence of two further tricycles necessary (cf. Scheme 8). However, in the temperature range of up to 85° these two further tricycles could not be detected by ¹H-NMR. When heated in the presence of excess ADM in decalin at 180°, the ‘missing’ tricyclic forms could be evidenced by their tetracyclic trapping products ‘anti’- 45 and ‘anti’- 48 , respectively (Scheme 9).     

Cyclopropanization of Methyl Carboxylates with Tebbe-Type Reagents

The methylenation reaction of methyl azulene-2-carboxylates (cf. Schemes 1 and 2) with Tebbe's or Takai's reagent is described. When the prescribed amount of Takai's reagent is applied in a four-fold excess, the corresponding cyclopropyl methyl ethers are formed instead of the enol ethers (cf. Schemes 2 and 3). Similarly, methyl benzoate and methyl 2-naphthoate yield, after treatment with Takai's reagent and hydrolysis, the corresponding cyclopropanols 18 and 19 , respectively (Scheme 3). The cyclopropyl methyl ether 4 or cyclopropanol 5 rearrange, on acid catalysis, into the l-(azulen-2-yl)propan-l-one 20 (Scheme 4). whose reduction with Et₃SiH in CF₃COOH yields the 2-propylazulene 21 .     

An Improved and Simplified Synthesis of 4-Styrylazulenes

It is shown that 4- or 8-[(E)-styryl]-substituted azulenes can easily be prepared from 4- or 8-methylazulenes in the presence of potassium tert-butoxide (t-BuOK) with the corresponding benzaldehydes in tetrahydrofuran (THF) at −5 to 25° (see Schemes 1 and 2). 6-(tert-Butyl)-4,8-dimethylazulene ( 5 ) with both Me groups in reactive positions leads to the formation of a mixture of the mono- and distyryl-substituted azulenes 6 and 7 , respectively (Scheme 3). Vilsmeier formylation of 6 results in the formation of 3 : 2 mixture of the azulene-carbaldehydes 8a and 8b , which can be separated by chromatography on silica gel. Reduction of 8a and 8b with NaBH₄ in trifluoroacetic acid (TFA)/CH₂Cl₂ gives the 1-methyl forms 9a and 9b , respectively, in good yields (Scheme 4). The latter two azulenes are not separable on silica gel.     

Thermal Reaction of Azulenes with Dimethyl Acetylenedicarboxylate in Supercritical Carbon Dioxide

1,3,4,6,8-Pentamethylazulene ( 9 ), when heated at 100° in supercritical CO₂ at 150 bar in the presence of 4 equiv. of dimethyl acetylenedicarboxylate (ADM), led to the formation of 16% of a 1:1 mixture of dimethyl 3,5,6,8,10-pentamethylheptalene-1,2-dicarboxylate 12a ) and its double-bond-shifted isomer 12b as well as 4% of the corresponding azulene-1,2-dicarboxylate 13 (Scheme 4). The formation of the [1 + 2] adduct 11 (cf. Scheme 2) was not observed. Similarly, benz[a]azulene ( 25 ) yielded in supercritical CO₂ (150°/170 bar) in the presence of 4 equiv. of ADM dimethyl benzo[d]heptalene-6,7-dicarboxylate ( 29 ; 30%) and dimethyl benzo[a]cyclopent[cd]azulene-1,2-dicarboxylate ( 28 ; 22%; Scheme 5). The reaction of 5,9-diphenylbenz[a]azulene ( 26 ) and ADM in supercritical CO₂ (100°/150 bar) gave the corresponding benzo[d]heptalene-6,7-dicarboxylate 31 (22%) and dimethyl 5,9-diphenyl-4b,10-etheno-10H-benz[a]azulene-11,12-dicarboxylate( 30 ; 25%; Scheme 5).     

Radical Arylation Reactions of 4, 6, 8-Trimethylazulene

The synthesis of 1- and 2-aryl-substituted (aryl = Ph, 4-NO₂? C₆H₄, and 4-MeO? C₆H₄) 4, 6, 8-trimethylazulenes ( 4 and 3 , respectively) in moderate yields by direct arylation of 4, 6, 8-trimethylazulene ( 8 ) with the corresponding arylhydrazines 13 in the presence of Cu^IIions in pyridine (see Scheme 4) as well as with 4-MeO? C₆H₄Pb(OAc)₃ ( 16 ) in CF₃COOH (see Scheme 5) is described. With 13 , also small amounts of 1, 2- and 1, 3-diarylated azulenes (see 14 and 15 , respectively, in Scheme 4) are formed. The 4-methoxyphenylation of 8 with 16 yielded also the 1, 1′-biazulene 17 in minor amounts (see Scheme 5). 4, 6, 8-Trimethyl-2-phenylazulene ( 3a ) was also obtained as the sole product in moderate yields by the reaction of sodium phenylclopentadienide ( 1a ) with 2, 4, 6-trimethylpyrylium tetrafluoroborate ( 2 ) in THF (Scheme 1). The attempted phenylation of 8 as well as of azulene ( 9 ) itself with N-nitroso-N-phenylacetamide ( 10 ) led only to the formation of the corresponding 1-(phenylazo)-substituted azulenes 12 and 11 , respectively (Scheme 3).     

Formation of Unusual Products from the Acid-Catalyzed Reaction of Azulenes with Dimethyl Acetylenedicarboxylate

The reaction of guaiazulene ( 4 ) and dimethyl acetylenedicarboxylate (ADM) in tetralin or toluene, catalyzed by 5 mol-% of trifluoroacetic acid (TFA) at ambient temperature, leads to the formation of the corresponding heptalene-4,5-dicarboxylate 6 and a guaiazulenyl-substituted 2,2a,4a,8b-tetrahydrocyclopent[cd]azulene derivative 7 beside the expected guaiazulenyl-substituted ethenedicarboxylates (E)- 5 and (Z)- 5 as main products (Scheme 2). The structure of 7 was unequivocally established by an X-ray crystal-structure analysis (Fig. 1). Precursor of 7 must be the 2a,4a-dihydrocyclopent[cd]azulene-3,4-dicarboxylate 9 which reacts, under TFA catalysis, with a second molecule of 4 (Scheme 3). No formation of products of type 7 has been observed in the TFA-catalyzed reaction of 4,6,8-trimethyl- and 1,4,6,8-tetramethylazulene ( 13 and 16 , respectively) and ADM (Scheme 4). On the other hand, the TFA-catalyzed reaction of azulene ( 18 ) itself and ADM at ambient temperature gives rise to a whole variety of new products (Scheme 5), the major part of which is derived from dimethyl 2a,4a-dihydrocyclopent[cd]azulene-3,4-dicarboxylate ( 25 ) as the main intermediate (Scheme 6). Nevertheless, for the formation of the 2a,4a,6,8b-tetrahydrocyclobut[a]azulene derivatives (E)- 24a and (E)- 24b , a corresponding 2a,8b-dihydro precursor 29 has to be postulated as crucial intermediate (Scheme 8).     

Asymmetric induction bny enantiotopically differentiating retro-claisen reaction of P{rochiral bicyclic β-diketones

The possibility of preparing cycloalkanones with an asymmetric β-C-atom by enantiotopically differentiating retro-Claisen reactions of bicyclic diketones a (Scheme l) is tested with the decalin-1,8-diones 1 and 7 , as well as with the bicyclo[3.3.0]octane-2,8-diones 10 and 11 . Treatment of the reactive dione 1 with chiral tetra-alkyl titanate catalysts results in a low optical induction (13%, Scheme 2). Cleavage with the Nasalts of a-amino-alcohols and hydrolysis of the resulting amides or esters gives much better optical yields, reaching 86% ee with dione 1 and (?)-ephedrine (Scheme 3). Almost as efficient is N-methylephedrine with 75% optical induction (Scheme 5). Lower enantiotopical differentiation is, however, observed with (?)-ephedrine and diones 7 (44% ee), 10 (8% ee), and 11 (48% ee) (Schemes 3 and 4, Table l), or with dione 1 and _L-prolinol (37% ee) or (?)-2-amino-1-butanol (11% ee) (Scheme 5, Table 2). The moderate chemical yields of these transformations (500–70%) can be ascribed to side-reactions of the ketones under the strongly basic conditions.     

Formation of Heptaleno[1,2-c]furans and Heptaleno[1,2-c]furanones

The dehydrogenation reaction of the heptalene-4,5-dimethanols 4a and 4d , which do not undergo the double-bond-shift (DBS) process at ambient temperature, with basic MnO₂ in CH₂Cl₂ at room temperature, leads to the formation of the corresponding heptaleno[1,2-c]furans 6a and 6d , respectively, as well as to the corresponding heptaleno[1,2-c]furan-3-ones 7a and 7d , respectively (cf. Scheme 2 and 8). The formation of both product types necessarily involves a DBS process (cf. Scheme 7). The dehydrogenation reaction of the DBS isomer of 4a , i.e., 5a , with MnO₂ in CH₂Cl₂ at room temperature results, in addition to 6a and 7a , in the formation of the heptaleno[1,2-c]-furan-1-one 8a and, in small amounts, of the heptalene-4,5-dicarbaldehyde 9a (cf. Scheme 3). The benzo[a]heptalene-6,7-dimethanol 4c with a fixed position of the C?C bonds of the heptalene skeleton, on dehydrogenation with MnO₂ in CH₂Cl₂, gives only the corresponding furanone 11b (Scheme 4). By [²H₂]-labelling of the methanol function at C(7), it could be shown that the furanone formation takes place at the stage of the corresponding lactol [3-²H₂]- 15b (cf. Scheme 6). Heptalene-1,2-dimethanols 4c and 4e , which are, at room temperature, in thermal equilibrium with their corresponding DBS forms 5c and 5e , respectively, are dehydrogenated by MnO₂ in CH₂Cl₂ to give the corresponding heptaleno[1,2-c]furans 6c and 6e as well as the heptaleno[1,2-c]furan-3-ones 7c and 7e and, again, in small amounts, the heptaleno[1,2-c]furan-1-ones 8c and 8e , respectively (cf. Scheme 8). Therefore, it seems that the heptalene-1,2-dimethanols are responsible for the formation of the furan-1-ones (cf. Scheme 7). The methylenation of the furan-3-ones 7a and 7e with Tebbe's reagent leads to the formation of the 3-methyl-substituted heptaleno[1,2-c]furans 23a and 23e , respectively (cf. Scheme 9). The heptaleno[1,2-c]furans 6a, 6d , and 23a can be resolved into their antipodes on a Chiralcel OD column. The (P)-configuration is assigned to the heptaleno[1,2-c]furans showing a negative Cotton effect at ca. 320 nm in the CD spectrum in hexane (cf. Figs. 3–5 as well as Table 7). The (P)-configuration of (–)- 6a is correlated with the established (P)-configuration of the dimethanol (–)- 5a via dehydrogenation with MnO₂. The degree of twisting of the heptalene skeleton of 6 and 23 is determined by the Me-substitution pattern (cf. Table 9). The larger the heptalene gauche torsion angles are, the more hypsochromically shifted is the heptalene absorption band above 300 nm (cf. Table 7 and 8, as well as Figs. 6–9).     

Reductive Elimination of Phenylsulfonyl Groups in the 3‐Position of Benzo[a]heptalene‐2,4‐diols

3‐(Phenylsulfonyl)benzo[a]heptalene‐2,4‐diols 1 can be desulfonylated with an excess of LiAlH₄/MeLi?LiBr in boiling THF in good yields (Scheme 6). When the reaction is run with LiAlH₄/MeLi, mainly the 3,3′‐disulfides 6 of the corresponding 2,4‐dihydroxybenzo[a]heptalene‐3‐thiols are formed after workup (Scheme 7). However, the best yields of desulfonylated products are obtained when the 2,4‐dimethoxy‐substituted benzo[a]heptalenes 2 are reduced with an excess of LiAlH₄/TiCl₄ at ?78→20° in THF (Scheme 10). Attempts to substitute the PhSO₂ group of 2 with freshly prepared MeONa in boiling THF led to a highly selective ether cleavage of the 4‐MeO group, rather than to desulfonylation (Scheme 13).     

Surprising Formation of Highly Substituted Azulenes on Thermolysis of 4,5,6,7,8‐Pentamethyl‐2H‐cyclohepta[b]furan‐2‐one and Heptalene Formation with the New Azulenes

Heating of 4,5,6,7,8‐pentamethyl‐2H‐cyclohepta[b]furan‐2‐one ( 1a ) in decalin at temperatures >170° leads to the development of a blue color, typical for azulenes. It belongs, indeed, to two formed azulenes, namely 4,5,6,7,8‐pentamethyl‐2‐(2,3,4,5,6‐pentamethylphenyl)azulene ( 4a ) and 4,5,6,7,8‐pentamethylazulene ( 5a ) (cf. Scheme 2 and Table 1). As a third product, 4,5,6,7‐tetramethyl‐2‐(2,3,4,5,6‐pentamethylphenyl)‐1H‐indene ( 6a ) is also found in the reaction mixture. Neither 4,6,8‐trimethyl‐2H‐cyclohepta[b]furan‐2‐one ( 1b ) nor 2H‐cyclohepta[b]furan‐2‐one ( 1c ) exhibit, on heating, such reactivity. However, heating of mixtures 1a / 1b or 1a / 1c results in the formation of crossed azulenes, namely 4,6,8‐trimethyl‐2‐(2,3,4,5,6‐pentamethylphenyl)azulene ( 4ba ) and 2‐(2,3,4,5,6‐pentamethylphenyl)azulene ( 4ca ), respectively (cf. Scheme 3). The formation of small amounts of 4,6,8‐trimethylazulene ( 5ba ) and azulene ( 5ca ), respectively, besides 1H‐indene 6a is also observed. The observed product types speak for an [8+2]‐cycloaddition reaction between two molecules of 1a or between 1b and 1c , respectively, with 1a , whereby 1a plays in the latter two cases the part of the two‐atom component (cf. Figs. 5 – 7 and Schemes 4 – 6). Strain release, due to the five adjacent Me groups in 1a , in the [8+2]‐cycloaddition step seems to be the driving force for these transformations (cf. Table 3), which are further promoted by the consecutive loss of two molecules of CO₂ and concomitant formation of the 10π‐electron system of the azulenes. The new azulenes react with dimethyl acetylenedicarboxylate (ADM) to form the corresponding dimethyl heptalene‐4,5‐dicarboxylates 20 , 22 , and 24 (cf. Scheme 7), which give thermally or photochemically the corresponding double‐bond‐shifted (DBS) isomers 20′ , 22′ , and 24′ , respectively. The five adjacent Me groups in 20 / 20′ and 24 / 24′ exert a certain buttressing effect, whereby their thermal DBS process is distinctly retarded in comparison to 22 / 22′ , which carry `isolated' Me groups at C(6), C(8), and C(10). This view is supported by X‐ray crystal‐structure analyses of 22 and 24 (cf. Fig. 8 and Table 5).     

Thermal Reaction of Highly Alkylated Azulenes with Dimethyl Acetylenedicarboxylate: HOMO(Azulene) vs. SHOMO(Azulene) Control in the Primary Thermal Addition Step

The reaction of highly alkylated azulenes with dimethyl acetylenedicarboxylate (ADM) in decalin or tetralin at 180–200° yields, beside the expected heptalene- and azulene-1,2-dicarboxylates, tetracyclic compounds of type ‘anti’- V and tricyclic compounds of type E (cf. Schemes 2–4 and 8–11). The compounds of type ‘anti’- V represent Diels-Alder adducts of the primary tricyclic intermediates A with ADM. In some cases, the tricyclic compounds of type E also underwent a consecutive Diels-Alder reaction with ADM to yield the tetracyclic compounds of type ‘anti’- or ‘syn’- VI (cf. Schemes 2 and 8–11). The tricyclic compounds of type E , namely 4 and 8 , reversibly rearrange via [1,5]-C shifts to isomeric tricyclic structures (cf. 18 and 19 , respectively, in Scheme 6) already at temperatures > 50°. Photochemically 4 rearranges to a corresponding tetracyclic compound 20 via a di-π-methane reaction. The observed heptalene- and azulene-1,2-dicarboxylates as well as the tetracyclic compounds of type ‘anti’'- V are formed from the primary tricyclic intermediates A via rearrangement (→heptalenedicarboxylates), retro-Diels-Alder reaction (→ azulenedicarboxylates), and Diels-Alder reaction with ADM. The different reaction channels of A are dependent on the substituents. However, the main reaction channel of A is its retro-Diels-Alder reaction to the starting materials (azulene and ADM). The highly reversible Diels-Alder reaction of ADM to the five-membered ring of the azulenes is HOMO(azulene)/LUMO(ADM)-controlled, in contrast to the at 200° irreversible ADM addition to the seven-membered ring of the azulenes to yield the Diels-Alder products of type E . This competing reaction must occur on grounds of orbital-symmetry conservation under SHOMO(azulene)/LUMO(ADM) control (cf. Schemes 20–22). Several X-ray diffraction analyses of the products were performed (cf. Chapt. 4.1).     

Thermal Reaction of Azulene and Some of Its Symmetrically Substituted Methyl Derivatives with Dimethyl Acetylenedicarboxylate

It is shown that azulene ( 1 ) and dimethyl acetylenedicarboxylate (ADM) in a fourfold molar excess react at 200° in decalin to yield, beside the known heptalene- ( 5 ) and azulene-1,2-dicarboxylates ( 6 ), in an amount of 1.6% tetramethyl (1RS,2RS,5SR,8RS)-tetracyclo[6.2.2.2^2,50^1,5]tetradeca-3,6,9,11,13-pentaene-3,4,9,10-tetracarboxylate(‘anti’-7) as a result of a SHOMO (azulene)/LUMO(ADM)-controlled addition of ADM to the seven-membered ring of 1 followed by a Diels-Alder reaction of the so formed tricyclic intermediate 16 (cf. Scheme 3) with a second molecule of ADM. The structure of ‘anti’-7 was confirmed by an X-ray diffraction analysis. Similarly, the thermal reaction of 5,7-dimehtylazulene ( 3 ) with excess ADM in decalin at 120° led to the formation of ca. 1% of ‘anti’- 12 , the 7,12-dimethyl derivative of‘anti’-7, beside of the corresponding heptalene- 10 and azulene-1,2-dicaboxylated (cf Scheme 2). The introduction of Me groups at C(1)and C(3)of azulene ( 1 ) and its 5,7-dimethyl derivative 3 strongly enhance the thermal formation of the corresponding tetracyclic compound. Thus, 1,3-dimethylazulene ( 2 ) in the presence of a sevenfold molar excess of ADM at 200° yielded 20% of ‘anti’- 9 beside an equal amount of dimethyl 3-mehtylazulene-1,2-dicarboxylate ( 8 ;cf. Scheme 1), and 1,3,5,7-tetramethylazulene ( 4 ) with a fourfold molar excess of ADM AT 200° gave a yield of 37% of‘anti’- 15 beside small amount of the corresponding heptalene- 13 and azulene-1,2-dicarboxylates 14 (cf.Scheme 2).     

A One‐Pot Biginelli Synthesis of 6‐Unsubstituted 5‐Aroylpyrimidin‐2(1H)‐ones and 6‐Acetyl‐1,2,4‐triazin‐3(2H)‐ones

The three‐component Biginelli‐like cyclocondensation reaction of enamines 1 , urea, and aldehydes in dioxane/acetic acid efficiently afforded the corresponding 6‐unsubstituted 3,4‐dihydropyrimidin‐2(1H)‐ones 2 in good yields (Scheme 1, Table). The corresponding reaction of azaenamine (=hydrazone) 7 with benzaldehyde and urea afforded 6‐acetyl‐1,2,4‐triazin‐3(2H)‐ones in good yields (Scheme 3).     

Bildung von 1,2,4-Trithiolanen in Dreikomponenten-Gemischen aus Phenyl-azid,aromatischen Thioketonen und 2,2,4,4-Tetramethylcyclobutanthionen: Eine Schwefel-Transfer-Reaktion unter Bildung von ‘Thiocarbonylthiolaten’ ((Alkylidensulfonio)thiolaten) als reaktive Zwischenstufen

Formation of 1,2,4-Trithiolanes in Three-Component Reactions of Phenyl Azide, Aromatic Thiones, and 2,2,4,4-Tetramethylcyclobutanethiones: A Sulfur-Transfer Reaction to ‘Thiocarbonyl-thiolates’ ((Alkylidenesulfonio)-thiolates) as Reactive Intermediates The reaction of PhN₃ and aromatic thioketones 18 (two-component reaction) at 80° yields only the corresponding imines 22 , S, and N₂. Under similar conditions, in the presence of sterically crowded 2,2,4,4-tetramethyl-cyclobutanethiones 19 (three-component reaction), 1,2,4-trithiolanes of type 20 are formed in good yields in addition to imines 22 (Scheme 4). In case of 19a and 19c (X = CO, CS), the symmetrical trithiolanes 21a and 21b , respectively, are also isolated. With 4,4-dimethyl-2-phenyl-1,3-thiazole-5(4H)-thione ( 24 ) instead of aromatic thioketone 18 , imine 25 , trithiolane 21a , and 1,4,2-dithiazolidine 26 are formed (Scheme 5). A reaction mechanism for the formation of 1,2,4-trithiolanes 20 and 21 , including an S-transfer to generate ‘thiocarbonyl-thiolates’ 2b and/or 2c and 1,3-dipolar cycloaddition with a thioketone, is proposed in Scheme 7.     

Ring-Transformation von Imidazolidin–2,4-dionen ( = Hydantoinen) zu 4H-Imidazolen bei der Umsetzung mit 3-(Dimethylamino)-2,2-dimethyl-2H -azirin

Ring Transformation of Imidazolidine-2,4-diones ( = Hydantoins) to 4H-Imidazoles in the Reaction with 3-(Dimethylamino)-2,2-dimethyl-2H-azirines At ca. 70°, 3-(dimethylamino)-2,2-dimethyl-2H -azirine ( 1 ) and 5,5-disubstituted hydantoins 4 in MeCN or i-PrOH give 2-(1-aminoalkyl)-5-(dimethylamino)-4,4-dimethyl-4H -imidazoles 5 in good yield (Scheme 2). These products are decarboxylated 1:1 adducts of 1 and 4 . A reaction mechanism is suggested in analogy to the previously reported reactions of 1 and NH-acidic heterocycles containing the CO? NH? CO? NH moiety (Scheme 5). The formation of ureas 6 and 7 can be rationalized by trapping the intermediate isocyanate F by an amine. No reaction is observed between 1 and 1,5,5- or 3,5,5-trisubstituted hydantoins in refluxing MeCN or i-PrOH, but an N-isopropylation of 1,5,5-trimethylhydantoin ( 8b ) occurs in the presence of morpholine (Scheme 3). The reaction of the bis(azirine)dibromozink complex 11 and hydantoines 4 in refluxing MeCN yields zink complexes 12 of the corresponding 2-(1-aminoalkyl)-4H -imidazoles 5 (Scheme 4).