Gas‐phase fragmentations of N‐methylimidazolidin‐4‐one organocatalysts

N‐methylimidazolidin‐4‐one organocatalysts were studied in the gas phase. Protonated and sodium‐cationized (sodiated) molecules are conveniently accessible by electrospray mass spectrometry. Protonation enables three different closed‐shell paths of ring cleavage leading to iminium ions. The fragmentation pattern is largely unaffected by exocyclic substituents and thus is valuable to characterize the substance type as N‐methylimidazolidin‐4‐ones. Sodiated species show a distinctly different fragmentation that is less useful for characterization purposes: apart from signal loss due to dissociation of Na⁺, the observation of benzyl radical loss is by far predominant. Only in absence of a benzyl substituent, an analogue of the third ring cleavage (loss of [C₂H₅NO]) is observed. Copyright © 2017 John Wiley & Sons, Ltd.     

Product and Mechanism of Gas‐phase Pyrolysis of 2‐arylidinehydrazinopyrimidines: Interesting Route to Condensed Heterocycles[1]

Gas‐phase pyrolysis of N‐arylidine‐N′‐pyrimidin‐2‐yl‐hydrazine derivatives 1a , 1b , 1c , 1d , 1e gave the corresponding arylnitriles 2a , 2b , 2c , 2d , 2e , 2‐aminopyrimidine 3 , 3‐phenyl‐1,2,4‐triazolo[4,3‐a]pyrimidines 4 , 2‐phenyl‐1,2,4‐triazolo[1,5‐a]pyrimidines 5 , 2,4,5‐triphenyl‐1H‐imidazole 6 , and 2,3‐diphenylquinoline 7 . The analyses of the reaction products are reported and used to elucidate the mechanism of the pyrolytic process.     

Gas‐phase fragmentation of protonated C60‐pyrimidine derivatives

Electrospray ionization mass spectrometry/mass spectrometry (ESI/MS/MS) and multiple stage mass spectrometry (MSⁿ, n > 2) were used in the positive ion mode, with two different types of mass spectrometers, a quadrupole time‐of‐flight and an ion trap, to characterize two sets of different types of C₆₀‐aminopyrimidine exohedral derivatives. In one set, the pyrimidine moiety bears an amino acid methyl ester residue, and in the other the pyrimidine ring is part of a nucleoside‐type moiety, the latter existing as two separated diastereoisomers. We have found that retro‐cycloaddition processes occur for the closed shell protonated species formed by electrospraying C₆₀ derivatives synthesized by Diels–Alder reactions, whereas for the C₆₀ derivatives synthesized via 1,3‐dipolar cycloadditions, these processes did not occur. Formation of diagnostic ions allowed the differentiation between the two groups of fullerene derivatives, and between the diastereoisomers of C₆₀ derivatives with a nucleoside‐type moiety. In general, the fragmentation processes are strongly dependent on the protonation sites and on the structure of the exohedral moieties. Copyright © 2009 John Wiley & Sons, Ltd.     

N‐arylhexahydropyrimidines. Part 1. Synthesis and 1H NMR characterization of 1,3‐Di and 1,2,3‐trisubstituted derivatives

A series of N‐arylhexahydropyrimidines la‐1 were synthesized by condensation of N‐aryl‐N'‐alkyl‐ (or aryl)‐1,3‐propanediamines 2a‐h with aldehydes. Reactions with formaldehyde proceeded in hydroalcoholic solution, while condensation with aromatic aldehydes required in general the use of activated molecular sieves. ¹H NMR spectra of compounds la‐1 were analyzed and the results correlated with their conforma‐tional features. Derivatives devoid of a 2‐substituent la‐g show fast ring reversal and N‐inversion. The presence of a 2‐aryl group shifts the ring reversal equilibrium towards conformations where the 2‐aryl substituent is equatorial. Differential assignment of axial and equatorial hydrogens in these compounds was made on the basis of coupling constants and chemical shift values. In compound 1k spectral data suggest the axial orientation of the N‐methyl group. Such findings were confirmed in the corresponding NOESY spectrum.     

Gas‐phase pyrolytic reactions of N‐ethyl,N‐isopropyl,and N‐t‐butyl substituted 2‐aminopyrazine and 2‐aminopyrimidine

The rates of gas‐phase elimination of N‐ethyl (1), N‐isopropyl (2), N‐t‐butyl (3) substituted 2‐aminopyrazine and N‐ethyl (4), N‐isopropyl (5), and N‐t‐butyl (6) substituted 2‐aminopyrimidine have been measured. The compounds undergo unimolecular first‐order pyrolytic reactions. The relative rates of the primary:secondary;tertiary alkyl homologues at 600 K are 1:14.4:38.0 for the pyrazines and 1:20.8:162.5 for the pyrimidines, respectively. The reactivities of these compounds have been compared with those of the alkoxy analogues and with each other. Product analyses, together with the kinetic data, were used to outline a feasible pathway for the elimination reaction of the compounds under study. © 2000 John Wiley & Sons, Inc. Int J Chem Kinet 32: 403–407, 2000     

Gas‐phase tautomerism in hydroxy azo dyes – from 4‐phenylazo‐1‐phenol to 4‐phenylazo‐anthracen‐1‐ol

The tautomeric constants of a series of azo dyes were estimated in the gas phase by using electron ionization mass spectrometry. It was shown that the relative amount of the keto tautomer increases from 4‐phenylazo‐1‐phenol to 4‐phenylazo‐anthracen‐1‐ol, thus confirming the quantum‐chemical predictions. The existence of the enol tautomer of 4‐phenylazo‐anthracen‐1‐ol is shown for the first time by mass spectrometry in the gas phase. This finding is supported by flash photolysis measurements in solution. Copyright © 2010 John Wiley & Sons, Ltd.     

Theoretical Study on Gas—phase Pyrolytic Reactions of N—Ethyl,Isopropyl and N—t—Butyl Substituted 2—Aminopyrazine

Density functional theory (DFT) and ab initio methods were used to study gas‐phase pyrolytic reaction mechanisms of iV‐ethyl, N‐isopropyl and N‐t‐butyl substituted 2‐aminopyrazine at B3LYP/6–31G* and MP2/6–31G*, respectively. Single‐point energies of all optimized molecular geometries were calculated at B3LYP/6–311 + G(2d,p) level. Results show that the pyrolytic reactions were carried out through a unimolecular first‐order mechanism which were caused by the migration of atom H(17) via a six‐member ring transition state. The activation energies which were verified by vibrational analysis and correlated with zero‐point energies along the reaction channel at B3LYP/6–311 + G(2d,p) level were 252.02 kJ. mo^?1 (N‐ethyl substituted), 235.92 kJ‐mol^?1 (N‐t‐isopropyl substituted) and 234.27 kJ‐mol^?1 (N‐t‐butyl substituted), respectively. The results were in good agreement with available experimental data.     

Gas‐phase pyrolysis in organic synthesis. Part 3: Novel cyclization of 2‐arylhydrazonopropanals into cinnolines1

3‐oxo‐3‐aryl‐2‐arylhydrazonopropanals (1) have been converted under thermal gas‐phase conditions cleanly into cinnolines (2) . A plausible mechanism is suggested to account for this transformation based on the kinetics and products of reaction. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 402–406, 2001     

Gas‐phase basicity of 2‐furaldehyde

2‐Furaldehyde (2‐FA), also known as furfural or 2‐furancarboxaldehyde, is an heterocyclic aldehyde that can be obtained from the thermal dehydration of pentose monosaccharides. This molecule can be considered as an important sustainable intermediate for the preparation of a great variety of chemicals, pharmaceuticals and furan‐based polymers. Despite the great importance of this molecule, its gas‐phase basicity (GB) has never been measured. In this work, the GB of 2‐FA was determined by the extended Cooks's kinetic method from electrospray ionization triple quadrupole tandem mass spectrometric experiments along with theoretical calculations. As expected, computational results identify the aldehydic oxygen atom of 2‐FA as the preferred protonation site. The geometries of O‐O‐cis and O‐O‐trans 2‐FA and of their six different protomers were calculated at the B3LYP/aug‐TZV(d,p) level of theory; proton affinity (PA) values were also calculated at the G3(MP2, CCSD(T)) level of theory. The experimental PA was estimated to be 847.9 ± 3.8 kJ mol^?1, the protonation entropy 115.1 ± 5.03 J mol^?1 K^?1 and the GB 813.6 ± 4.08 kJ mol^?1 at 298 K. From the PA value, a ΔH°_f of 533.0 ± 12.4 kJ mol^?1 for protonated 2‐FA was derived. Copyright © 2012 John Wiley & Sons, Ltd.     

Gas‐phase pyrolytic reaction of 3‐phenoxy and 3‐phenylsulfanyl‐1‐propanol derivatives: Kinetic and mechanistic study

3‐Phenoxy‐1‐propanols 1a–c and 3‐phenylsulfanyl‐1‐propanols 2a–c containing primary, secondary, and tertiary alcohols were prepared and subjected to gas‐phase pyrolysis in a static reaction system. Pyrolysis of 4‐phenyl‐1‐butanol 3 , 2‐methyl‐3‐phenyl‐1‐propanol 4 , and 2‐methyl‐3‐phenylpropanoic acid 5 was also studied, and results were compared with those obtained for compounds 1–3 . The pyrolytic reactions were homogeneous and followed a first‐order rate equation. Analysis of the pyrolysate showed the products to be phenol (from 1a to 1c ), thiophenol (from 2a to 2c ), and toluene (from 3 to 5 ) and carbonyl compounds. The kinetic results and product analysis of each of the nine investigated compounds are rationalized in terms of a plausible transition state for the elimination pathway. © 2007 Wiley Periodicals, Inc. 40: 51–58, 2008     

Gas‐phase tautomerism in 1‐phenylazonaphthalene‐4‐ol: verification of the responses of individual tautomers

Gas‐phase tautomerism in 1‐phenylazonaphthalene‐4‐ol (1) was studied by using electron ionization (EI) mass spectrometry on the basis of the fragmentations of the model enol and keto tautomers, where the movable proton is replaced by a methyl group. These fixed tautomers were obtained as an easy separable mixture by simple methylation of the cheap and easily accessible diazene (1). It was found that their EI mass spectral fragmentations are in full congruence with the already published theoretical predictions. The relative energies required for bond cleavage in 1 and its fixed tautomers were estimated by stepwise increasing of the electron energy of the ion source of the mass spectrometer. A simple equation for the approximate estimation of the molar fractions of the individual tautomers was suggested. It was shown that the enol form is dominant in the temperature range of 200–300°C. Copyright © 2009 John Wiley & Sons, Ltd.     

Gas‐phase fragmentation of γ‐lactone derivatives by electrospray ionization tandem mass spectrometry

Fragmentation reactions of β‐hydroxymethyl‐, β‐acetoxymethyl‐ and β‐benzyloxymethyl‐butenolides and the corresponding γ‐butyrolactones were investigated by electrospray ionization tandem mass spectrometry (ESI‐MS/MS) using collision‐induced dissociation (CID). This study revealed that loss of H₂O [M + H ?18]⁺ is the main fragmentation process for β‐hydroxymethylbutenolide (1) and β‐hydroxymethyl‐γ‐butyrolactone (2). Loss of ketene ([M + H ?42]⁺) is the major fragmentation process for protonated β‐acetoxymethyl‐γ‐butyrolactone (4), but not for β‐acetoxymethylbutenolide (3). The benzyl cation (m/z 91) is the major ion in the ESI‐MS/MS spectra of β‐benzyloxymethylbutenolide (5) and β‐benzyloxymethyl‐γ‐butyrolactone (6). The different side chain at the β‐position and the double bond presence afforded some product ions that can be important for the structural identification of each compound. The energetic aspects involved in the protonation and gas‐phase fragmentation processes were interpreted on the basis of thermochemical data obtained by computational quantum chemistry. Copyright © 2009 John Wiley & Sons, Ltd.     

Gas-phase thermolysis of thieno[3,2-e][1,2,4]triazines. Interesting routes towards heterocyclic ring systems

Gas-phase thermolysis of thieno[3,2-e][1,2,4]triazines gave benzonitrile, isothiazole, pyrimidine, [1]benzothieno[2,3-d]pyrimidine and thieno[3,2-d]thiazole derivatives. A mechanism of these pyrolytic transformation was proposed. Two new and efficient syntheses of the starting thieno[3,2-e][1,2,4]triazines were reported.     

1H and 13C chemical shifts for acridines: Part XVIII. 9‐Chloroacridine and 9‐(N‐allyl)‐ and 9‐(N‐propargyl)acridinamine derivatives

The¹H and ¹³C NMR resonances for acridine derivatives 9‐substituted with chloro, allylamino and propargylamino groups were completely assigned using a concerted application of gs‐COSY, gs‐HMQC and gs‐HMBC experiments. 9‐(N‐Allyl)‐ and 9‐(N‐propargyl)acridinamine derivatives present amino–imino tautomerism including a large broadening of ¹H and ¹³C NMR signals at room temperature. To obtain suitable resolution, therefore, these latter compounds were studied at 370 K in DMSO‐d6 solutions and showed a complete shift towards the imino tautomers. Copyright © 2003 John Wiley & Sons, Ltd.     

Gas‐phase pyrolysis of 2‐heteroaromatic‐1‐dimethylaminoethylenes: Kinetic and mechanistic study

Gas‐phase pyrolysis reactions of 4(2′‐dimethylaminoethenyl)‐2‐oxo‐2H‐benzo[b]pyran‐3‐carbonitrile ( 1 ), 4(2′‐dimethylaminoethenyl)‐2‐oxo‐2H‐naphtho[1,2‐b]pyran‐3‐carbonitrile ( 2 ), 1,6‐dihydro‐4‐(2′‐dimethylaminoethenyl)‐6‐oxo‐1‐phenylpyridazine‐3,5‐dicarbonitrile ( 3 ), 2‐cyano‐5‐dimethylamino‐3‐phenyl‐2,4‐pentadienonitrile ( 4 ), 2‐cyano‐5‐dimethylamino‐3‐(2‐thienyl)‐2,4‐pentadienonitrile( 5 ), 1,2‐dihydro‐4‐(2′‐dimethylaminoethenyl)‐oxo‐quinoline‐4‐carbonitrile ( 6 ), 6‐(ethylthio)‐4‐(2′‐dimethylaminoethenyl)‐2‐phenylpyrimidine‐5‐carbonitrile ( 7 ) (Scheme 1) have been carried out. The rates of gas‐phase pyrolytic reactions of compounds 3, 4, 5, and 7 have been measured and found to correspond to unimolecular first‐order reactions. Product analyses together with kinetic data were used to outline a feasible pathway for the pyrolytic reactions of the compounds under study. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:47–51, 2001     

Biologically active 1‐arylpiperazines. Synthesis of N‐[3‐(4‐aryl‐1‐piperazinyl)propyl] derivatives of benzoxazinone and benzoxazolinone

The synthesis of new N‐[3‐(4‐aryl‐1‐piperazinyl)propyl] derivatives of 1H‐2,4‐benzoxazin‐3(4H)‐one ( 1a‐b ), 2H‐1,4‐benzoxazin‐3(4H)‐one ( 2a‐b, 3a‐b and 4b ), and benzoxazolin‐2‐one ( 5a‐b ), as biologically active agents, is described.     

Gas-phase thermolysis of 1-acylnaphtho[1,8-de][1,2,3]triazines. Interesting direct routes towards condensed naphtho[1,8-de]heterocyclic ring systems

FVP pyrolysis of 1-acylnaphtho[1,8-de][1,2,3]triazines at 500 °C and 10⁻² Torr gave exclusively the corresponding 2-substituted naphtho[1,8-de][1,3]oxazines. The latter was also obtained by static pyrolysis but in lower yield along with the corresponding N-(naphthalen-1-yl)acylamides. The reaction was studied kinetically and mechanistically.     

Synthesis and tuberculostatic activity of novel N′‐methyl‐4‐(pyrrolidin‐1‐yl)picolinohydrazide and N′‐methylpyrimidine‐2‐carbohydrazide derivatives

The synthesis of N′‐methyl‐4‐(pyrrolidin‐1‐yl)picolinohydrazide and N′‐methyl‐pyrimidine‐2‐carbohydrazide derivatives ( 5a and 5b ) was carried out. These compounds were used as starting materials to obtain methyl N′‐methylhydrazinecarbodithioates 6a and 6b , which, on reaction with either triethylamine or hydrazine, gave corresponding 1,3,4‐oxadiazioles 7a and 7b or 1,2,4‐triazoles 9a and 9b with the free NH₂ group at the N‐4 position, respectively. Compounds 8a – e , particularly containing cyclic amines at N‐4 of the 1,2,4‐triazole ring, were also obtained. Synthesized compounds were tested in vitro for their activity against Mycobacterium tuberculosis. The structure–activity relationship analysis for obtained compounds was done. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:223–230, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21008