Flash Vacuum Pyrolysis Conditions Research Articles

Thermal Rearrangement of Azulenes to Naphthalenes: A Deeper Insight into the Mechanisms.

The thermal rearrangement of azulene to naphthalene has been the subject of several experimental and computational studies. Here, we reexamine the proposed mechanisms at the DFT level. The use of different functionals showed that the HF-exchange contribution significantly affects reaction energies and barrier heights. Accordingly, all proposed pathways were investigated with the optimal method, M06-2X/6-311+G(d,p), which confirms the norcaradiene-vinylidene mechanism (A) as the dominant unimolecular route (Ea ≈ 76 kcal/mol) able to account for the major products of pyrolyses using 13C- or substituent-labeled azulenes. Moreover, a facile vinylidene-acetylene interconversion will scramble the terminal carbon atoms in the vinylidene. Several other potential intramolecular reaction mechanisms (B-E) are ruled out because of higher activation energies (>84 kcal/mol) and failure to reproduce the results obtained with substituted and 13C-labeled azulenes and benzazulenes. These experimental results also demonstrate that the proposed free radical or H atom-induced intermolecular methylene walk and spiran mechanisms cannot be major contributors, especially under flash vacuum pyrolysis conditions.

On the Regioselectivity of the Gould–Jacobs Reaction: Gas‐Phase Versus Solution‐Phase Thermolysis

A detailed investigation of the regioselectivity in the thermal cyclization of (pyridyl)aminomethylenemalonates both in the gas‐ and solution phase is presented. Flash vacuum pyrolysis (FVP) as a gas‐phase thermolysis technique is used to study the Gould–Jacobs reaction at temperatures between 450–650 °C, while different solution‐phase heating techniques (reflux, microwave, and continuous flow) were employed at 260–350 °C. Depending on the position of the substituent in the pyridine moiety and the applied thermolysis technique, the regioselectivity of the cyclization can be controlled either in favor of the kinetic (pyridopyrimidinone) or the thermodynamic (naphthyridinone) product. Under FVP conditions, 6‐substituted pyridopyrimidinones were obtained in high regioselectivity, which was not demonstrated before under standard Gould–Jacobs reaction conditions. DFT calculations have been additionally performed to provide further insights into the mechanistic pathways of this specific Gould–Jacobs reaction.

Synthesis of cis-syn-cis and cis-anti-cis linear triquinanes via photo-thermal metathesis

Diverse cis-syn-cis and cis-anti-cis triquinane frameworks have been assembled by a simple synthetic protocol starting with substituted cage diones under microwave irradiation conditions. Thermal fragmentation of the cyclobutane ring play a key role in this process and milder reaction conditions have been employed in contrast to normal flash vacuum pyrolysis conditions. Here, thermal isomerization of the double bond has also been realized under the microwave irradiation conditions to afford the isomeric triquinanes at low temperature. These triquinane units are considered to be useful for the total synthesis of natural products and non-natural products containing fused cyclopentane rings.

Realization of Photo‐Thermal Metathesis Under Microwave Irradiation Conditions: An Entry to Triquinane Frameworks

AbstractWe report a simple and convenient synthetic route to cis,syn,cis triquinane frameworks under microwave irradiation conditions starting with cage diones. This is feasible because of the substituents present in the precursors, which facilitate the metathesis under milder reaction conditions as compared to normal flash vacuum pyrolysis conditions (∼600 °C). Isomerization of the double bond was realized under microwave irradiation to deliver the other triquinanes, which are useful precursors for natural product synthesis.

Rearrangements of Nitrile Imines: Ring Expansion of Benzonitrile Imines to Cycloheptatetraenes and Ring Closure to 3-Phenyl-3 H-diazirines.

Nitrile imines are important intermediates in 1,3-dipolar cycloaddition reactions, and they are also known to undergo efficient, unimolecular rearrangements to carbodiimides via 1 H-diazirines and imidoylnitrenes under both thermal and photochemical reaction conditions. We now report a competing rearrangement, revealed by CASPT2(14,12) and B3LYP calculations, in which C-phenylnitrile imines 8 undergo ring expansion to 1-diazenyl-1,2,4,6-cycloheptatetraenes 12 akin to the phenylcarbene-cycloheptatetraene rearrangement. Amino-, hydroxy-, and thiol-groups in the meta positions of C-phenylnitrile imine lower the activation energies for this rearrangement so that it becomes potentially competitive with the cyclization to 1 H-diazirines and hence rearrange to carbodiimides. The diazenylcycloheptatetraenes 12 thus formed can evolve further to cycloheptatetraene 30 and 2-diazenyl-phenylcarbene 16 over modest activation barriers, and the latter carbenes cyclize very easily to 2 H- and 3 H-indazoles, from which 6-methylenecyclohexadienylidene, phenylcarbene, fulvenallene, and their isomers are potentially obtainable. Moreover, another new rearrangement of benzonitrile imine forms 3-phenyl-3 H-diazirine, which is a precursor of phenyldiazomethane and hence phenylcarbene. This reaction is competitive with the ring expansion. The new rearrangements predicted here should be experimentally observable, for example, under matrix photolysis or flash vacuum pyrolysis conditions.

Structure and thermal reactivity of some 2-substituted 1,3-oxathiolane S-oxides

ABSTRACTIsomerization of 2-benzylidene-1,3-dioxolane to 3-phenylbutyrolactone occurs readily under flash vacuum pyrolysis (FVP) conditions. 2-Diphenylmethyl-1,3-oxathiolane and 2-benzyl-1,3-oxathiolane have been prepared and the latter compound has been oxidized to the corresponding sulfoxide, whose structure and conformation are examined by 1H NMR, and to the sulfone whose X-ray structure is determined. 2-Benzylidene-1,3-oxathiolane is also prepared and the behavior of the three S-oxidized oxathiolane derivatives upon FVP is examined. While extrusion of SOn to give ethene and a carbonyl compound predominates in all three cases, the sulfoxide gives also bis(2-hydroxyethyl) disulfide, most likely formed via thiirane S-oxide and 1,2-oxathietane.

Versatile Pyrolytic Synthesis of Fused Polycyclic Heteroaromatic Compounds

Thirty-six new stabilised phosphonium ylides designed to undergo thermal loss of Ph3PO and radical domino cyclisation have been prepared and are generally found to undergo the desired reaction under flash vacuum pyrolysis conditions at 850 °C. A wide range of ­tetra- and pentacyclic fused-ring heterocycles, many previously unknown, are thus formed in moderate to high yield in a single step. By using suitably substituted starting materials, substituents such as CH3 and Cl can be installed at various positions in the products. The method has also been demonstrated in a combinatorial mode to generate a small library of twelve fused-ring heterocycles in a single pyrolysis.

Isomerization of perchlorohexatriene in three consecutive rearrangements to perchloro-2-vinylbutadiene

Perchlorohexatriene isomerizes in three subsequent rearrangements to perchloro-2-vinylbutadiene. A radical-induced Z-E-equilibration of linear perchlorohexatrienes is followed by cyclization to a methylenecyclopentene. Under flash-vacuum pyrolysis conditions, a ring contraction to 1,2-dimethylenecyclobutane occurs. In the condensed phase, a radical-induced ring opening generates the branched perchloro-vinylbutadiene. All compounds are converted to hexachlorobenzene, but only at very high temperatures.

Ring Contraction in Arylcarbenes and Arylnitrenes; Rearrangements of 1- and 3-Isoquinolylcarbenes and 2-Naphthylnitrene to Cyanoindenes.

Flash vacuum pyrolysis (FVP) of 1-(5-(13)C-5-tetrazolyl)isoquinoline 18 generates 1-((13)C-diazomethyl)isoquinoline 19 and 1-isoquinolyl-((13)C-carbene) 22, which undergoes carbene-nitrene rearrangement to 2-naphthylnitrene 23. The thermally generated nitrene 23 is observed directly by matrix-isolation ESR spectroscopy, but undergoes ring contraction to a mixture of 3- and 2-cyanoindenes 26 and 27 under the FVP conditions. The (13)C label distribution in the cyanoindenes was determined by (13)C NMR spectroscopy and indicates the occurrence of two parallel paths of ring contraction starting from 1-isoquinolylcarbene; path a via ring expansion to 3-aza-benzo[c]cyclohepta-1,2,4,6-tetraene 32 bifurcating to 2-naphthylnitrene 23 and 2-aza-benzobicyclo[3.2.0]heptatriene 39 (paths a1 and a2); and path b via ring closure of the carbene onto the ring nitrogen, yielding 1-aza-benzo[d]bicyclo[4.1.0]hepta-2,4,6-triene 34 and 3-aza-benzo[d]cyclohepta-2,3,5,7-tetraene 35. Product studies demand that the major path is route a1 via 2-naphthylnitrene 23, which then undergoes direct ring contraction to 1-cyanoindene; but the (13)C label distribution requires that the non-nitrene route b contributes significantly. The two reaction paths are modeled at the B3LYP/6-31G* level. The initially formed carbene 22 is estimated to carry chemical activation of some 40 kcal/mol. This allows both reaction channels to proceed simultaneously under low-pressure FVP conditions. FVP of 3-(5-tetrazolyl)isoquinoline 28 similarly generates 3-diazomethylisoquinoline 29 and 3-isoquinolylcarbene 30, which rearranges to 3- and 2-cyanoindenes 26 and 27.

Chemistry of aza- and diazafulvenium methides in heterocyclic synthesis

Abstract Aza- and diazafulvenium methide systems are versatile building blocks for the synthesis of pyrroles and pyrazoles. These extended dipoles participate in sigmatropic [1,8]H shifts and 1,7-electrocyclizations giving vinyl pyrroles and pyrazoles. Under flash vacuum pyrolysis conditions these heterocycles undergo interesting rearrangements. Aza- and diazafulvenium methides can be intercepted by dipolarophiles. Derivatives with carboxylate groups at C-4 and/or C-5 act exclusively as 1,7-dipoles affording products resulting from the addition across the 1,7-positions. These 1,7-cycloadducts include chlorin and bacteriochlorin type macrocycles as well as steroidal analogues, compounds with relevance in medicinal chemistry. In contrast with this chemical behavior, 5-trifluoromethylazafulvenium methides can participate in both 1,7- and 1,3-dipolar cycloadditions. The generation and reactivity of benzodiazafulvenium methides is also discussed.

Isomerization and fragmentation pathways of 1,2-azaborine.

The generation of 1,2-azaborine (4), the BN-analogue of ortho-benzyne, was recently achieved by elimination of tert-butyldimethylchlorosilane under the conditions of flash vacuum pyrolysis. The present investigation identifies by computational means pathways for the thermal isomerization and fragmentation of 1,2-azaborine. The computations were performed using single reference (hybrid/density functional, second order Møller-Plesset perturbation, and coupled cluster theories) as well as multiconfiguration methods (complete active space SCF based second order perturbation theory, multireference configuration interaction, and multiconfiguration coupled electron pair approximation) with basis sets up to polarized triple-ζ quality. The 1,2-azaborine is, despite the distortion of its molecular structure, the most stable C4H4BN isomer investigated. The formation of BN-endiyne isomers is highly unfavorable as the identified pathways involve barriers close to 80 kcal mol(-1). The concerted fragmentation to ethyne and 2-aza-3-bora-butadiyne even has a barrier close to 120 kcal mol(-1). The fragmentation of BN-enediynes has energetic requirements similar to enediynes.

Stone-Wales Rearrangements in Hydrocarbons: From Planar to Bowl-Shaped Substrates.

Carbene, cyclobutyl, and potential diradical mechanisms were studied computationally for Stone-Wales rearrangements in several derivatives of as-indacene and pyracyclene, including cyclopent[hi]acephenanthrylene, dicyclopenta[cd,fg]pyrene, corannulene, diindeno[1,2,3,4-defg;1',2',3',4'-mnop]chrysene, and semibuckminsterfullerene. At the UM06-2X/cc-pVDZ and BD(T)/cc-pVDZ//UM06-2X/cc-pVDZ levels of theory, free energies of reaction reveal that transformations involving an increase in curvature are thermodynamically unfavorable. In addition, the carbene transition states or intermediates (corrected to 1000 °C) are generally around 100-120 kcal/mol higher than starting substrates, except for as-indacene (80 kcal/mol), which is the only process considered here that is predicted to have a barrier accessible under typical flash vacuum pyrolysis conditions. For pyracyclene derivatives, the relative free energy of cyclobutyl intermediates rises steadily with increasing curvature of the substrate and increasing annelation. Singlet acetylenic diradicals related to pyracyclene, diindenochrysene, and semibuckminsterfullerene are predicted to be second- or higher-order saddle points that lie more than 40 kcal/mol higher than the corresponding carbenes and cyclobutyl intermediates.

1‐Methyl‐5‐(trifluoromethyl)azafulvenium Methide, an Intermediate That Undergoes Reaction through “Unusual” cis‐exo‐1,3‐ and trans‐exo‐1,7‐Cycloadditions

AbstractThe generation and reactivity of a new 1‐methyl‐5‐(trifluoromethyl)azafulvenium methide are described. Under microwave‐induced pyrolysis conditions this intermediate could be trapped by dipolarophiles, acting either as a 4π or as an 8π dipole. Quantum chemical calculations carried out at the DFT level of theory allowed the rationalization of the results observed in the cycloaddition of 1‐methyl‐5‐(trifluoromethyl)azafulvenium methide and N‐substituted maleimides. The study revealed that for 1,7‐cycloadducts the major products are obtained in the trans configuration through the unusual exo‐cycloaddition mode, whereas for 1,3‐cycloadducts the cis counterparts are obtained from this unexpected approach. In addition, under flash vacuum pyrolysis or conventional thermolysis conditions 1‐methyl‐5‐(trifluoromethyl)azafulvenium methide undergoes an allowed suprafacial sigmatropic [1,8]H shift leading to the formation of 2‐methyl‐3‐(trifluoromethyl)‐1‐vinyl‐1H‐pyrrole.

Probing Mechanisms of Aryl–Aryl Bond Cleavages under Flash Vacuum Pyrolysis Conditions

Several biaryls have been subjected to flash vacuum pyrolysis (FVP) at 1100°C and 0.8–0.9 hPa. Product compositions are reported for the FVP of 9-phenylanthracene (1), 2-bromobiphenyl (5), biphenyl (8), 1,10-diphenylanthracene (12), 9-(2-naphthyl)anthracene (17), and 9,9′-bianthracenyl (20). The experimental results have been used to evaluate four possible mechanistic pathways for the cleavage of aryl–aryl bonds under these conditions: (1) the ‘explosion’ of substituted phenyl radicals; (2) hydrogen atom attachment to an ipso-carbon atom of the biaryl followed by C–C bond cleavage; (3) direct homolysis; and (4) loss of a fragment as an aryne. None of these mechanisms by itself successfully accommodates all of the experimental facts. The data suggest that aryl–aryl bond cleavages under FVP conditions involve at least two different mechanistic pathways and that the relative contributions of the competing pathways probably vary from one biaryl to the next.

Roger F. C. Brown Memorial Issue

Roger F. C. Brown Memorial Issue

Transfer Reagents 4: Retro-Diels–Alder Routes to 3,6-Di(2-pyridyl)pyridazinonorbornadiene, a Test Bed for the Relative Dienofugacity of Isobenzofuran, Isoindole, and Anthracene

Norbornadiene cycloadducts reacted with 3,6-di(2-pyridyl)-s-tetrazine to produce pyridazines (diene-protected alkenes), following dehydrogenation (by DDQ) of the intermediate dihydropyridazines. The title 3,6-di(2-pyridyl)-pyridazinonorbornadiene was produced under flash vacuum pyrolysis conditions by ejection of anthracene (590 °C), isobenzofuran (630 °C) or isoindole (580 °C) from the corresponding pyridazines, establishing the following dienofugacity order: isoindole > anthracene > isobenzofuran. Calculations of the respective retro-Diels–alder activation energies at the B3LYP/6-31G* level of theory correctly predicted the experimentally found isobenzofuran > anthracene > isoindole order. Cavity bis-3,6-di(2-pyridyl)-pyridazine (dppn) and chevron-shaped bis-dppn ligands were prepared from the title compound by coupling at the norbornene π-bond.

Highly Efficient Dehydrogenation of 5‐Benzyl‐3‐phenyl‐2‐thioxoimidazolidin‐4‐one: Microwave versus Flash Vacuum Pyrolysis Conditions

Abstract5‐Benzyl‐3‐phenyl‐2‐thioxoimidazolidin‐4‐one underwent thermal dehydrogenation to afford 5‐benzylidene‐2‐thioxoimidaxolidin‐4‐one under microwave and flash vacuum pyrolysis conditions. A high predominance of the Z‐isomer over the E‐isomer of the imidazolidinone product was achieved. By using DFT and NBO calculations, the mechanism of the dehydrogenation and the selectivity were also explored.

Gas-phase generation and cyclisation reactions of imidoyl radicals

Some 1,2-diarylimidoyl radicals were generated in the gas-phase by intramolecular radical translocation from ortho-imino-aryloxyl radicals, in turn generated under flash vacuum pyrolysis (FVP) conditions. The imidoyls reacted with XR ortho'-substituents in the N-aryl group to give (in most cases) modest yields of cyclisation products. Depending on the nature of the bridging atom (X), the formation of these products was initiated either by a further hydrogen atom translocation (X = CH(2)), or by ipso-attack onto the aryl group (R = Ph), or by direct substitution at the heteroatom (X = S). With XR = N(Me)Ph, the major reaction product was probably the result of a competing pathway not involving the corresponding imidoyl.

Stereochemical deuterium‐labeling study on the denitrogenation of 7,7‐diethoxy‐2,3‐diazabicyclo[2.2.1]hept‐2‐ene

A stereochemical deuterium‐labeling study of the thermal and photochemical denitrogenation of the exo‐selectively dideuterated azoalkane 7,7‐diethoxy‐2,3‐diazabicyclo[2.2.1]hept‐2‐ene (AZb‐d2) was performed in order to obtain information about the denitrogenation mechanism of 2,3‐diazabicyclo[2.2.1]hept‐2‐ene derivatives. A double‐inversion product 5,5‐diethoxybicyclo[2.1.0]pentane (CPb), that is, inv‐CPb, was selectively formed over the retention product ret‐CPb in a ratio of inv‐CPb/ret‐CPb = 73/27 under flash vacuum pyrolysis (FVP) conditions (365 °C/~1.0 × 10−2 mmHg). The formation of inv‐CPb was slightly higher than that of ret‐CPb in the direct photolysis of AZb‐d2 at 70 °C. An approximately 1:1 mixture of the two products was observed after the direct photolysis at 7 °C. A stereoselective formation of 1,5‐diethoxycyclopent‐1‐ene (MG‐d2) was found in the denitrogenation of AZb‐d2 under the FVP conditions. Computational studies at the broken‐symmetry (BS)‐(U)CCSD/6‐31G(d) level of theory revealed that the stepwise C–N bond cleavage is the energetically favored process of the denitrogenation mechanism. The SH2 trajectory of the nitrogen‐extrusion process through an equatorial conformation of the intermediary diazenyl diradical DZb‐eq was found for the formation of inv‐CPb. An alternative route for inv‐CPb was found through an axial conformation of DZb‐ax, which was suggested by the trajectory calculations using a Born–Oppenheimer molecular dynamics at the UB3LYP/6‐31G(d). Copyright © 2011 John Wiley & Sons, Ltd.

ChemInform Abstract: Intramolecular Ene Reactions of Thioaldehydes Giving α-Mercapto Lactones.

The crystalline acids 3b, 4b and 5b and 6b, formally cycloadducts of anthracene, 9,10-dimethylanthracene and cyclopentadiene, respectively, with thioxoacetic acid (HO2CCHS), have been used to prepare esters with various allylic and homoallylic alcohols. These esters dissociated when heated, either in toluene under reflux or under the conditions of flash vacuum pyrolysis (FVP), to liberate transient thioaldehydes (thioxoacetate esters), which underwent intramolecular ‘ene’ reactions. Thus, the anthracene derivative 3c, in toluene at 111 °C gave, via prenyl thioxoacetate 2c, cis-2-mercapto-3-isopropenylbutyrolactone 13 in good yield. The corresponding cyclopentadiene derivatives 5c and 6c gave the same product, as a mixture of cis and trans isomers, essentially quantitatively when subjected to FVP. Similar experiments, involving Type [1, 1] intramolecular ene reactions, gave the α-mercapto-γ-lactones 20, 21 and 22, and the epimeric amercapto-δ-lactones 26. Further, the cyclopentadiene adduct 6h of 2-methylprop-2-enyl thioxoacetate 2h gave, under FVP conditions, the α-mercapto-δ-lactone 27 by a Type [2, 1] ene reaction. Evidence supporting a concerted mechanism for the ene reactions is discussed.Improved preparations of the cycloadducts 3b and 4b of thioxoacetic acid 2b with anthracene and dimethylanthracene, respectively, are recorded.