An efficient synthesis of 2-(guaiazulen-1-yl)furan derivatives via intramolecular Wittig reactions

An efficient and mild synthesis of 2-(guaiazulen-1-yl)furans,starting from easily accessible 1-(3-aryl-2-cyanopropenoyl) guaiazulenes,tributylphosphine and acyl chlorides,is described.The strategy employs the intramolecular Wittig protocol as a key step to append the crticial furan ring,leading to the highly functional furans in good yields.     

Reactions of (1R,2S)-1,2-di(2-furyl)-1,2-di(3-guaiazulenyl)ethane and (1R,2S)-1,2-di(3-guaiazulenyl)-1,2-di(2-thienyl)ethane with tetracyanoethylene (TCNE) in benzene: comparative studies on the products and their spectroscopic properties

Reactions of the title meso forms, (1R,2S)-1,2-di(2-furyl)-1,2-di(3-guaiazulenyl)ethane (1) and (1R,2S)-1,2-di(3-guaiazulenyl)-1,2-di(2-thienyl)ethane (2), with a two molar amount of TCNE in benzene at 25 °C for 5 h (for 1) and 48 h (for 2) under oxygen give new compounds, 2,2,3,3-tetracyano-4-(2-furyl)-8-isopropyl-6-methyl-1,4-dihydrocyclohepta[c,d]azulene (3) and 2,2,3,3-tetracyano-8-isopropyl-6-methyl-4-(2-thienyl)-1,4-dihydrocyclohepta[c,d]azulene (4), respectively, in 74 and 21% isolated yields. Comparative studies on the above reactions as well as the spectroscopic properties of the unique products 3 and 4, possessing interesting molecular structures, are reported and, further, a plausible reaction pathway for the formation of these products is described.     

Reactions of azulene and guaiazulene with all-trans-retinal and trans-cinnamaldehyde: comparative studies on spectroscopic, chemical, and electrochemical properties of monocarbenium-ions stabilized by expanded π-electron systems with an azulenyl or 3-guaiazulenyl group

Reaction of azulene (1) with all-trans-retinal in diethyl ether in the presence of hexafluorophosphoric acid at −10 °C for 1 h in a dark room gives the corresponding monocarbenium-ion compound, (2E,4E,6E,8E)-1-azulenyl-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ylium hexafluorophosphate (3), in 74% isolated yield. The spectroscopic, chemical, and electrochemical properties of 3 compared with those of the previously-documented (2E,4E,6E,8E)-1-(3-guaiazulenyl)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ylium hexafluorophosphate (4) are reported. Along with the above delocalized monocarbenium-ion compounds 3 and 4, stabilized by the expanded π-electron systems possessing an azulenyl (or 3-guaiazulenyl) group, an efficient preparation as well as the spectroscopic, chemical, and electrochemical properties of (2E)-1-azulenyl-3-phenyl-2-propen-1-ylium and (2E)-1-(3-guaiazulenyl)-3-phenyl-2-propen-1-ylium hexafluorophosphates (5 and 6) (90 and 96% isolated yields), having a similar partial structure [i.e., the (2E)-1-azulenyl-2-propen-1-ylium-ion or (2E)-1-(3-guaiazulenyl)-2-propen-1-ylium-ion part] to those of 3 and 4, is documented. Moreover, the crystal structure of 6, whose carbenium-ion framework is planar, is shown.     

Coloring Carbohydrates: Investigation of Azulene Derivatives as Blue Protecting Groups

Coloring carbohydrate derivatives by a chromophore tag greatly facilitates all purification steps during a synthetic sequence, according to a methodology called “chromophore-supported purification” (CSP). Herein an Fmoc-analogous blue protective group for CSP is introduced, based on guaiazulene. Following a mechanistic rational, the synthesis and introduction of this new protecting group is shown, together with its removal under variable conditions and its application for the synthesis of glycoclusters of a glycopeptide and glycopeptoid type.     

Reaction of guaiazulene with o-formylbenzoic acid in diethyl ether (or methanol) in the presence of hexafluorophosphoric acid: comparative studies on H and C NMR spectral properties of 3-guaiazulenylmethylium- and 3-guaiazulenium-ion structures

Reaction of guaiazulene (1) with o-formylbenzoic acid (2) in diethyl ether in the presence of hexafluorophosphoric acid at 25 °C for 90 min gives the corresponding monocarbenium-ion compound, [2-(carboxy)phenyl](3-guaiazulenyl)methylium hexafluorophosphate (3), quantitatively, which upon treatment with aq NaHCO₃ leads to 3-(3-guaiazulenyl)-2-benzofuran-1(3H)-one (5) in 96% isolated yield. Similarly, reaction of 1 with 2 in methanol under the same conditions as the above reaction affords two kinds of inseparable monocarbenium-ion compounds, 3 and (3-guaiazulenyl)[2-(methoxycarbonyl)phenyl]methylium hexafluorophosphate (4) with an equilibrium between them, which upon reaction with a solution of NaBH₄ in ethanol at 25 °C for 30 min leads to 5 in 46% isolated yield and (3-guaiazulenyl)[2-(methoxycarbonyl)phenyl]methane (6) in 37% isolated yield. Along with the ¹H and ¹³C NMR spectral properties of a solution of 5 in trifluoroacetic acid-d₁ at 25 °C, whose molecular structure is converted to a ca. 1:1 equilibrium mixture of 7 possessing a partial structure of the 3-guaiazulenylmethylium-ion and 8 possessing a partial structure of the 3-guaiazulenium-ion, comparative studies on the ¹H and ¹³C NMR spectral properties of 7 and 8 with those of the monocarbenium-ion compound, (3-guaiazulenyl)[4-(methoxycarbonyl)phenyl]methylium hexafluorophosphate (A), 5, and 6 are reported. From these NMR studies, it can be inferred that the positive charge of the 3-guaiazulenylmethylium-ion part of 7 apparently is transferred to the seven-membered ring, generating a resonance form of the 3-guaiazulenylium-ion structure η′, and the same result can be inferred for the previously documented monocarbenium-ion compounds A-I. Moreover, referring to a comparative study on the C-C bond lengths of A observed by the X-ray crystallographic analysis with those of the optimized (3-guaiazulenyl)[4-(methoxycarbonyl)phenyl]methylium-ion structure for A calculated by a WinMOPAC (Ver. 3.0) program using PM3, AM1, or MNDOD as a semiempirical Hamiltonian, the optimized [2-(carboxy)phenyl](3-guaiazulenyl)methylium-ion structure for 3 calculated using PM3 is described.     

Preparation, crystal structure, and spectroscopic, chemical, and electrochemical properties of (2E,4E)-4-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)-1,3-butadiene compared with those of (E)-2-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)ethylene

Wittig reaction of 3-[4-(dimethylamino)phenyl]propanal (5) with (3-guaiazulenylmethyl)triphenylphosphonium bromide (4) in ethanol containing NaOEt at 25 °C for 24 h under argon gives the title (2E,4E)-1,3-butadiene derivative 6E in 19% isolated yield. Spectroscopic properties, crystal structure, and electrochemical behavior of the obtained new extended π-electron system 6E, compared with those of the previously reported (E)-2-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)ethylene (12), are documented. Furthermore, reaction of 6E with 1,1,2,2-tetracyanoethylene (TCNE) in benzene at 25 °C for 24 h under argon affords a new Diels-Alder adduct 8 in 59% isolated yield. Along with spectroscopic properties of the [π4+π2] cycloaddition product 8, the crystal structure, possessing a cis-3,6-substituted 1,1,2,2-tetracyano-4-cyclohexene unit, is shown. Moreover, reaction of 6E with (E)-1,2-dicyanoethylene (DCNE) under the same reaction conditions as the above gives no product; however, this reaction in p-xylene at reflux temperature (138 °C) for four days under argon affords a new Diels-Alder adduct 9 in 54% isolated yield. Although reaction of 6E with DCNE in toluene at reflux temperature (110 °C) for four days under argon provides 9 very slightly, reaction of 6E with dimethyl acetylenedicarboxylate (DMAD) in toluene at reflux temperature for two days under argon yields a new Diels-Alder adduct 10, in 58% isolated yield, which upon oxidation with MnO₂ in CH₂Cl₂ at 25 °C for 1 h gives 11, converting a (CH₃)₂N-4″ into CH₃NH-4″ group, in 37% isolated yield. The crystal structure of 11 supports the molecular structure 10 possessing a partial structure cis-3,6-substituted 1,2-dimethoxycarbonyl-1,4-cyclohexadiene. The title basic studies on the above are reported in detail.     

Preparation, structures, and haptotropic rearrangement of novel dinuclear ruthenium complexes, (μ2,η:η-guaiazulene)Ru2(CO)4(CNR)

Novel isonitrile derivatives of a diruthenium carbonyl complex, (μ₂,η³:η⁵-guaiazulene)Ru₂(CO)₅ (2), were synthesized by substitution of a CO ligand by an isonitrile, and were subjected to studies on thermal and photochemical haptotropic interconversion. Treatment of 2 (a 45:55 mixture of two haptotropic isomers, 2-A and 2-B) with RNC at room temperature resulted in coordination of RNC and alternation of the coordination mode of the guaiazulene ligand to form (μ₂,η¹:η⁵-guaiazulene)Ru₂(CO)₅(CNR), 5d–5f, [5d; R=^tBu, 5e; 2,4,6-Me₃C₆H₂, or 5f; 2,6-ⁱPr₂C₆H₃] in moderate to good yields. Thermal dissociation of a CO ligand from 5 at 60 °C resulted in quantitative formation of a desirable isonitrile analogue of 2, (μ₂,η³:η⁵-guaiazulene)Ru₂(CO)₄(CNR), 4d–4f, [4d; R=^tBu, 4e; 2,4,6-Me₃C₆H₂, or 4f; 2,6-ⁱPr₂C₆H₃], as a 1:1 mixture of the two haptotropic isomers. A direct synthetic route from 2 to 4d–4f was alternatively discovered; treatment of 2 with one equivalent of RNC at 60 °C gave 4d–4f in moderate yields. All of the new compounds were characterized by spectroscopy, and structures of 5d (R=^tBu) and 4d-A (R=^tBu) were determined by crystallography. Thermal and photochemical interconversion between the two haptotropic isomers of 4d–4f revealed that the isomer ratios in the thermal equilibrium and in the photostatic state were in the range of 48:52–54:46.     

Reactions of guaiazulene with thiophene-2,5-dicarbaldehyde and furan-2,5-dicarbaldehyde in methanol in the presence of hexafluorophosphoric acid: a facile preparation and properties of delocalized dicarbenium-ion compounds stabilized by two 3-guaiazulenyl groups and a thiophene (or furan) ring

Reaction of guaiazulene (1) with thiophene-2,5-dicarbaldehyde (2) in methanol in the presence of hexafluorophosphoric acid at 25 °C for 3 h gives as high as 90% isolated yield of the delocalized dicarbenium-ion compound, 2,5-thienylenebis(3-guaiazulenylmethylium) bis(hexafluorophosphate) (3). Similarly, reaction of 1 with furan-2,5-dicarbaldehyde (4) under the same conditions as the above reaction affords the corresponding dicarbenium-ion compound, 2,5-furylenebis(3-guaiazulenylmethylium) bis(hexafluorophosphate) (5), in 84% isolated yield. Along with a facile preparation and the spectroscopic and electrochemical properties of 3 and 5, comparative studies on the ¹H and ¹³C NMR spectral and chemical properties of 3 and 5 with those of the delocalized mono- and dicarbenium-ion compounds [i.e., (3-guaiazulenyl)(2-thienyl)methylium hexafluorophosphate (7), (2-furyl)(3-guaiazulenyl)methylium hexafluorophosphate (9), α,α′-bis(3-guaiazulenylmethylium) bis(tetrafluoroborate) (10), 1,2-phenylenebis(3-guaiazulenylmethylium) bis(hexafluorophosphate) (11), and 1,4-phenylenebis(3-guaiazulenylmethylium) bis(tetrafluoroborate) (12)] are reported. Moreover, referring to the results of the X-ray crystallographic analyses of 7, 9, 11, and 12, the optimized 2,5-thienylenebis(3-guaiazulenylmethylium)- and 2,5-furylenebis(3-guaiazulenylmethylium)-ion structures for 3 and 5, calculated by a WinMOPAC (version 3.0) program using PM3 as a semiempirical Hamiltonian, are described.     

Reaction of azulene with 1,2-bis[4-(dimethylamino)phenyl]-1,2-ethanediol in a mixed solvent of methanol and acetonitrile in the presence of hydrochloric acid: a facile one-pot synthesis and properties of new triarylethylenes possessing an azulen-1-yl group

Reaction of azulene (1) with 1,2-bis[4-(dimethylamino)phenyl]-1,2-ethanediol (2) in a mixed solvent of methanol and acetonitrile in the presence of 36% hydrochloric acid at 60 °C for 3 h gives 2-(azulen-1-yl)-1,1-bis[4-(dimethylamino)phenyl]ethylene (3) (8% yield), 1-(azulen-1-yl)-(E)-1,2-bis[4-(dimethylamino)phenyl]ethylene (4) (28% yield), and 1,3-bis{2,2-bis[4-(dimethylamino)phenyl]ethenyl}azulene (5) (9% yield). Besides the above products, this reaction affords 1,1-di(azulen-1-yl)-2,2-bis[4-(dimethylamino)phenyl]ethane (6) (15% yield), a meso form (1R,2S)-1,2-di(azulen-1-yl)-1,2-bis[4-(dimethylamino)phenyl]ethane (7) (6% yield), and the two enantiomeric forms (1R,2R)- and (1S,2S)-1,2-di(azulen-1-yl)-1,2-bis[4-(dimethylamino)phenyl]ethanes (8) (6% yield). Furthermore, addition reaction of 3 with 1 under the same reaction conditions as the above provides 6, in 46% yield, which upon oxidation with DDQ (=2,3-dichloro-5,6-dicyano-1,4-benzoquinone) in dichloromethane at 25 °C for 24 h yields 1,1-di(azulen-1-yl)-2,2-bis[4-(dimethylamino)phenyl]ethylene (9) in 48% yield. Interestingly, reaction of 1,1-bis[4-(dimethylamino)phenyl]-2-(3-guaiazulenyl)ethylene (11) with 1 in a mixed solvent of methanol and acetonitrile in the presence of 36% hydrochloric acid at 60 °C for 3 h gives guaiazulene (10) and 3, owing to the replacement of a guaiazulen-3-yl group by an azulen-1-yl group, in 91 and 46% yields together with 5 (19% yield) and 6 (13% yield). Similarly, reactions of 2-(3-guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene (12) and 1,1-bis{4-[2-(dimethylamino)ethoxy]phenyl}-2-(3-guaiazulenyl)ethylene (13) with 1 under the same reaction conditions as the above provide 10, 2-(azulen-1-yl)-1,1-bis(4-methoxyphenyl)ethylene (16), and 1,3-bis[2,2-bis(4-methoxyphenyl)ethenyl]azulene (17) (93, 34, and 19% yields) from 12 and 10 and 2-(azulen-1-yl)-1,1-bis{4-[2-(dimethylamino)ethoxy]phenyl}ethylene (18) (97 and 58% yields) from 13.     

An efficient preparation, crystal structures, and properties of monocarbenium-ion compounds stabilized by 3-guaiazulenyl and anisyl groups

Reaction of guaiazulene (1) with 2-methoxybenzaldehyde (2) in methanol in the presence of hexafluorophosphoric acid at 25 °C for 2 h gives (3-guaiazulenyl)(2-methoxyphenyl)methylium hexafluorophosphate (5a) in 93% yield. Similarly, reaction of 1 with 3-methoxybenzaldehyde (3) or 4-methoxybenzaldehyde (4) under the same reaction conditions as for 2 affords (3-guaiazulenyl)(3-methoxyphenyl)methylium hexafluorophosphate (6) (91% yield) or (3-guaiazulenyl)(4-methoxyphenyl)methylium hexafluorophosphate (7) (97% yield). The crystal structures as well as the spectroscopic, electrochemical, and chemical properties of these monocarbenium-ion compounds, possessing interesting resonance forms, stabilized by the 3-guaiazulenyl and anisyl (i.e., 2-, 3-, or 4-methoxyphenyl) groups are reported.