Hydrogen migrations in mass spectrometry. VI—the chemical ionization mass spectra of substituted benzoic acids and benzyl alcohols

The H₂ and CH₄ chemical ionization mass spectra of a series of series of substituted benzoic acids and substituted benzyl alcohols have been determined. For the benzoic acids the major fragmentation reactions of the protonated molecule involve elimination of H₂O or elimination of CO₂, the latter reaction involving migration of the carboxylic hydrogen to the aromatic ring. For the benzyl alcohols the major fragmentation reactions of [MH]⁺ involve loss of H₂O or CH₂O, analogous to the CO₂ elimination reaction for the benzoic acids. It is shown that the CO₂ and CH₂O elimination reactions occur only when a conjugated aromatic ring system is present, and that for the carboxylic acid systems, methyl groups and, to a lesser extent, phenyl groups are capable of migrating. The only discernible effect of substituents on the fragmentation of [MH]⁺ is an enhancement of the H₂O loss reaction in the benzoic acid system when an amino, hydroxyl, or halogen substituent is ortho to the carboxyl function. This ‘ortho’ effect, which differs in scope from that observed in electron impact mass spectra, is attributed to an intramolecular catalysis by the ortho substituent of the 1,3 hydrogen migration in the carbonyl protonated acid followed by H₂O elimination. Apparently, this route is favoured over the direct elimination of H₂O from the carbonyl protonated acid, since the latter has a high activation energy barrier because of unfavourable orbital symmetry restrictions.     

A study of the ortho effects and rearrangement processes in the mass spectra of 2-arylaminothiazine and -thiazoline derivatives

The behaviour of the title compounds under electron impact has been investigated using low and high resolution mass spectrometry and partial ¹⁵N and D labelling. A number of ions produced by rearrangement were observed. Abundant ions are formed by intramolecular ortho substitution reactions (cyclizations), as demonstrated by energetic and kinetic considerations and by studying the decomposition pathways of these ions. The ortho substitution processes involve loss or rearrangement of an ortho group of the aromatic ring.     

Intra- and intermolecular reactions of aromatic radical cations: An account of mechanistic concepts and methods in mass spectrometry

Investigations in the authors's laboratory in Bielefeld and elsewhere on the mechanism of the intramolecular and intermolecular aromatic substitution via radical cations are reviewed with the aim of presenting an example for the development of mass spectrometric methods and concepts for the study of the mechanisms of gaseous ionic reactions. An intramolecular aromatic substitution resulting in the loss of a hydrogen or a substituent from an aromatic ring of the molecule ions by the attack of a nucleophilic heteroatom in the side-chain was first observed in the normal electron impact (EI) mass spectra and was studied by substituent effects on ion abundance, ionization energy and appearance energy. This led to the construction of a two-step mechanism of the intramolecular aromatic substitution with a rate-determining first addition step. Subsequently, this fragmentation reaction was studied for a series of systems by tandem mass spectrometry, confirming the two-step mechanism and yielding an excellent insight into the dynamics of the substitution process. The bimolecular variety of the nucleophilic aromatic substitution via radical cations was investigated recently by Fourier transform ion cyclotron resonance spectrometry. The results for a series of halogenated benzenes and NH₃, CH₃NH₂ and (CH₃)₂NH as the nucleophile corroborate the conclusions drawn from the study of unimolecular reaction mechanisms. It is shown that in all cases the formation and further reaction of the addition intermediate play a crucial role. This can be perceived by the application of the configuration mixing reactivity model to the addition reaction, and by the concept of classical and distonic radical cations. This review on a specific reaction mechanism shows clearly the excellent techniques and methods which the developments in mass spectrometry have provided for a detailed study of the mechanisms of ionic reactions in the gas phase.     

Skeletal rearrangement of allyl acetates after protonation by chemical ionization

In the methane chemical ionization mass spectra of allyl phenylacetate and allyl phenoxyacetate the major reaction paths (>40%σ) involve skeletal rearrangements, which have no analogy in the corresponding, simpler electron-impact spectra. Substituent and deuterium labeling studies suggest a mechanism involving intramolecular substitution of the phenyl ring by the allyl group. Abstraction of hydrogen from the ortho position of the phenyl ring or from the rearranged allyl group is followed by expulsion of water and carbon monoxide.     

The mass spectra of styryl sulfoxides and sulfones

A variety of rearrangement reactions have been documented in the gas phase ion chemistry of styryl sulfoxides and sulfones. The styryl group rearranges from sulfur to oxygen as evidenced by loss of SCH₃ from methyl styryl sulfoxide and loss of SOCH₃ from the corresponding sulfone. The resulting m/e 119 ion loses carbon monoxide in one fragmentation route and alternatively loses a hydrogen atom from the aromatic nucleus to produce the benzofuran molecule ion via an electrophilic aromatic ring closure reaction. Styryl sulfoxides lose both carbon monoxide and formyl radicals directly from their molecule ions, but the corresponding sulfones do not fragment in this manner. The mechanisms of the above reactions, as well as others, were investigated using substituent and deuterium labeling. The styryl group has been shown to migrate in preference to a phenyl or substituted phenyl group by investigation of the mass spectra of appropriate aryl styryl sulfoxides and sulfones.     

Synthesis, Characterization and Weak Intramolecular Interactions of Porphyrins Bearing Nucleobases

5,10, 15-Triphenyl-20-{2- [α- (adenine-9 ) acetylamino]} phenyl porphyrin ( 1 ), 5,10, 15-triphenyl-20-{2-[α-(cytosine-1)acetylamino]} phenyl porphyrin (2), 5, 10, 15-triphenyl-20-{4-[α-(cytosine-1)ethoxy]} phenyl porphyrin (3) and their zinc complexes Zn-1, Zn-2 and Zn-3 have been prepared and characterized by ^1H NMR spectra, elemental analyses, electronic absorption spectra and mass spectra (FAB). Intramolecular π-π interactions and intramolecular metal-~ interaction for 1, 2, Zn-1,and Zn-2 have been investigated by several methods. ^1H NMR studies demonstrate that the porphyrin π-system in 1 and 2 is parallel to the adenine and the cytosine aromatic ring, respectively. The electronic absorption spectral properties of free porphyrin derivatives and their zinc complexes have been compared with those of H2TPP and ZnTPP. The results show that the UV-vis spectra of 1 and 2 are the same as that of H2TPP,whereas the spectra of their zinc complexes show 7 nm red shifts of the Soret bands compared to that of ZnTPP. The emission spectra of Zn-1 and Zn-2 are independent of excitation wavelength. From combination of the evidence of absorption and emission spectra it is suggested the existence of intramolecular metal-π interaction in Zn-1 and Zn-2. The results of conformational analysis agreed quite nicely with that of experiments, thus it was further to validate the experimental conclusions.     

Aluminium Chloride‐Catalyzed Intermolecular vs Intramolecular Friedel‐Crafts Reaction of Acrylanilides and 3‐Chloropropanamides

3‐Phenylpropionanilide ( 4a ) is obtained in a yield of 89% from acrylanilide by the treatment with AlCl₃/benzene, compared with a yield of 39% by the 1,4‐conjugate addition of phenyllithium. The formation of 4a indicated that an intermolecular Friedel‐Crafts reaction occurred, rather than the relatively more facile intramolecular ring cyclization, and provided a more efficient route than a conjugate addition of phenyllithium for the preparation of 3‐phenylpropionanilide and its derivatives. Although the methoxy group is an activator of the nucleophilic substitution, introduction of a methoxy substituent at N‐phenyl did not increase the competitive capability of the intramolecular cyclization because of AlCl₃‐catalyzed demethylation to form the ArOAlCl₂ complex which decreased the availability of the π‐electron in the N‐phenyl aromatic system.     

Mechanism of the grafting of organosilanes on mineral surfaces. IV. Phenylderivatives of sepiolite and poly (organosiloxanes)

Grafting reactions of phenyl groups on silica substrates using as reagents various phenylsilanes with variable distances between the silicon atoms and the aromatic ring by 0, 1, and 2 methylene groups [Si–(CH₂) _n –C₆H₅] were studied. Two different silicates have been selected as source of silica: sepiolite and tetraethyl-orthosilicate (TEOS). Sulfonic- and nitro-derivatives prepared from these phenyl compounds by electrophilic substitution reactions, have been obtained. The mechanism of these processes has been studied in relation to the number of methylene separating groups belonging to the starting reagents. The characterization of such systems has been achieved by XRD,²⁹Si and¹³C NMR/MAS, IR, and laser microprobe mass spectrometry.Parts I, II and III published in this Journal (1978) 256:135–139, (1979) 257:178–181 and (1985) 263:1025–1030     

Electron impact mass spectrometry of some 2,11-diaza[3.3]cyclophane derivatives

The most significant mass spectral features of thirteen title compounds are discussed with the aid of high-resolution mass measurements and metastable peak analysis. The decomposition patterns of the compounds investigated are strongly affected by N-substitution and by methyl substituents ortho to the bridging chains (ortho effects). A unique feature connected with symmetrical macrocycles, bearing at least two ortho methyl substituents on each phenyl ring, is the presence in their spectra of diagnostically important peaks, corresponding to [M ? RNH₂]⁺˙ and [M ? 2RNH₂]⁺˙ (R = Ts, H, CH₃). These daughter ions are proposed to be associated with the formation of cage compounds (multibridged cyclophanes), generated by an intramolecular [4 + 4] cycloaddition reaction of unstable linear bis-(o-xylylene) precursors.     

Experimental and Theoretical Investigation of an Azaoxyallyl Cation-Templated Intramolecular Aryl Amination Leading to Oxindole Derivatives

Herein, development and detailed investigation of a S_N′-type intramolecular aromatic substitution reaction involving α-arylazaoxyallyl cation intermediate, is disclosed. The study showcased that while α-aryl-α-chlorohydroxamate could be activated by a combination of base and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) into the corresponding azaoxyallyl cations, it could further emerge into a π-extended species involving the adjacent α-aryl moiety, and this transition is contingent on electronic effects of the aromatic ring as well as on α-substituents. An effective activation of the α-aromatic ring could pave the path for intramolecular Ar(Csp²)-N bond formation towards oxindoles. Control experiments and DFT calculations suggested that a non-pericyclic nucleophilic amination pathway is most likely operative and precluded the possibility of concerted or electrophilic amination mechanism. HFIP as the reaction solvent plays pivotal roles in the transformation.     

Transition‐Metal‐Free Intramolecular Carbene Aromatic Substitution/Büchner Reaction: Synthesis of Fluorenes and [6,5,7]Benzo‐fused Rings

Intramolecular aromatic substitution and Büchner reaction have been established as powerful methods for the construction of polycyclic compounds. These reactions are traditionally catalyzed by Rh^II catalysts with α‐diazocarbonyl compounds as the substrates. Herein a transition‐metal‐free intramolecular aromatic substitution/Büchner reaction is presented. These reactions use readily available N‐tosylhydrazones as the diazo compound precursors and show wide substrate scope.     

Bond Length Alternation and Internal Dynamics in Model Aromatic Substituents of Lignin

Broadband microwave spectra were recorded over the 2-18 GHz frequency range for a series of four model aromatic components of lignin; namely, guaiacol (ortho-methoxy phenol, G ), syringol (2,6-dimethoxy phenol, S ), 4-methyl guaiacol ( MG ), and 4-vinyl guaiacol ( VG ), under jet-cooled conditions in the gas phase. Using a combination of ¹³C isotopic data and electronic structure calculations, distortions of the phenyl ring by the substituents on the ring are identified. In all four molecules, the r_C(1)-C(6) bond between the two substituted C-atoms lengthens, leading to clear bond alternation that reflects an increase in the phenyl ring resonance structure with double bonds at r_C(1)-C(2), r_C(3)-C(4) and r_C(5)-C(6). Syringol, with its symmetric methoxy substituents, possesses a microwave spectrum with tunneling doublets in the a-type transitions associated with H-atom tunneling. These splittings were fit to determine a barrier to hindered rotation of the OH group of 1975 cm⁻¹, a value nearly 50 % greater than that in phenol, due to the presence of the intramolecular OH⋅⋅⋅OCH₃ H-bonds at the two equivalent planar geometries. In 4-methyl guaiacol, methyl rotor splittings are observed and used to confirm and refine an earlier measurement of the three-fold barrier V₃=67 cm⁻¹. Finally, 4-vinyl guaiacol shows transitions due to two conformers differing in the relative orientations of the vinyl and OH groups.     

Mass spectometry of aralkyl compounds with a functional group—VI1: Mass spectra of 1-phenylethyanol-1, 2-phenylethanol-1 and 1-phenylpropanol-2

Mass spectra of 1-phenylethanol-1 and its analogues, specifically deuterated in the aliphatic chain, suggest that the [M? CH₃]⁺ ion is represented partly by an α-hydroxybenzyl fragment. Moreover, the molecular ion loses successively—after scrambling of all hydrogen atoms, except those of CH₃? a hydrogen atom and C₆H₆, generation the CH₃CO⁺ ion. Diffuse peaks, found in the spectra of of 2-phenylethanol-1 and its analogues, specifically deuterated in the aliphatic chain and in the phenyl ring, show that the molecular ion loses C₂H₄O, possibly via a four-center mechanism, after an exchange of aromatic and hydroxylic hydrogens. Mass spectra of 1-phenylpropanol-2 and its analogues, specifically, deuterated in the aliphatic chain, demonstrate that in the molecular ion exclusively the hydroxyl hydrogen atom is transferred to one of the ortho-positions of the phenyl ring via a McLafferty rearrangement, generating the [M ? C₂H₄O]⁺ ion. Furtherore, an eight-membered ring structure is proposed for the [M ? CH₃]⁺ ion to explain the loss of H₂O and C₂H₂O from this ion after an extensive scrambling of hydrogen atoms.     

Mass spectra of a series of 2-p-substituted phenyl-1,3,2-dioxaborolanes

The mass spectra of a series of 2-p-substituted phenyl-1,3,2-dioxaborolanes have been examined and compared with the mass spectrum of 2-phenyl-1,3,2-dioxaborolane. Formation of the substituted ion [C₇H₆X]⁺ by electron impact induced rearrangement has been found to be influenced significantly by the presence and nature of the substituent at the para position of the phenyl ring.     

ALIPHATIC THIOETHERS BY S-ALKYLATION OF THIOLS VIA TRIALKYL BORATES

A simple and convenient one-pot procedure is described for the synthesis of thioethers via boron esters. This procedure involves in-situ generation of alkyl sulfates by reaction of trialkyl borates with concentrated sulfuric acid and subsequent reaction with thiols in the presence of pyridine. The reactions with boron esters of primary or secondary alcohols proceed cleanly at 100°C and afford aliphatic thioethers in reasonable yields (59–93%) within 24 h. Interestingly, the ¹H NMR spectra of the products showed no sign of positional isomerisms. The method fails however with thiophenol and does not yield aromatic thioethers, due to electrophilic substitution at the phenyl ring.     

Nitrogen bridgehead compounds. Part 80 unusual reaction of ethyl 9-bromo-4-oxo-6,7,8,9-tetr ahydro-4h-pyrido[1,2-a]pyrimidine-3-carboxylates and N-Methylaniline

The acid-catalysed intramolecular nucleophilic addition of the phenyl ring to the C(9a) = N(1) double bond of ethyl 9-(N-methyl-N-phenyl)-4-oxotetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carboxylates, formed in the reactions of ethyl 9-bromo-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carboxylates and N-methylaniline, gave the first examples of a new tetracyclic pyrimido[1′,2′:1,2]pyrido[3,2-b]indole ring system ( 7 ). X-ray diffraction analysis of 7a revealed that the annelation of the pyrimidine and piperidine rings is transoid, while that of the piperidine and pyrroline rings is cis, the piperidine ring adopts an unusual ⁶T₈ twisted boat conformation, while the pyrroline ring has a ⁹T_8a conformation.     

Cinnamoyl shikonin

The title compound, 1-(5,8-di­hydro-1,4-di­hydroxy-5,8-dioxo-2-naphthyl)-4-methyl­pent-3-en-1-yl cinnamate, C₂₅H₂₂O₆, crystallizes in space group P2₁. The phenyl ring of the cinnamate is anti to the carbonyl group of the same moiety [C—C—C—C = −175.6 (2)°] and is nearly parallel to the naphthyl ring system. Two six-membered rings formed by intramolecular hydrogen bonds, with O—H⃛O distances of 2.587 (2) and 2.589 (2) Å, occur on either side of the fused ring system, creating a tetracyclic pyrene-shaped system. The phenyl ring forms an intermolecular stack with the benzo­quinone ring, as a result of aromatic π–π interactions.     

Nucleophilic Aromatic Substitution Reactions of meso‐Bromosubporphyrin: Synthesis of a Thiopyrane‐Fused Subporphyrin

meso‐Bromosubporphyrin undergoes nucleophilic aromatic substitution (S_NAr) reactions with arylamines, diarylamines, phenols, ethanol, thiophenols, and n‐butanethiol in the presence of suitable bases to provide the corresponding substitution products. The S_NAr reactions also proceed well with pyrrole, indole, and carbazole to provide substitution products in moderate to good yields. Finally, the S_NAr reaction with 2‐bromothiophenol and subsequent intramolecular peripheral arylation reaction affords a thiopyrane‐fused subporphyrin.     

Dual Chromophoric Meso-Aryl BODIPYs with Aggregation Induced Red-Emission Characteristics: Optical Properties and their Application in Fe3+ Detection

Herein, we report the design of meso-aryl BODIPYs as a structural motif for aggregation-caused quenching (ACQ) to aggregation-induced emission (AIE) transformation. A series of meso-aryl BODIPY derivatives were synthesized, by systematically increasing the size of the chromophore at the meso-position from phenyl to pyrene. The effect of various factors, such as the aryl ring size, solvents, viscosity, and metal cations, on the photophysical properties was analyzed. The emission properties are well correlated with the flexibility of the aromatic ring for free rotation around the C_aryl−C_BODIPY bond. Accordingly, meso-phenanthrene BODIPY ( PhB ) has the highest emission characteristics. The emission property of less bulky aryl-substituted BODIPYs increases by increasing the solvent viscosity. The interaction of Fe³⁺ ions with aryl-BODIPYs provides a prominent photophysical response based on Lewis-acid supported decomplexation of BF₂ in aryl-BODIPYs. The bichromophoric meso-aryl BODIPYs exhibit notable intramolecular excitation energy transfer from the aromatic ring to the BODIPY core, which is higher in meso-anthracene BODIPY( AB ). Hence, decorating BODIPYs with polycyclic aromatic systems generates a twisted structure, which inhibits the π-π stacking between the planar aromatic molecules. This can be proposed as an effective approach at the molecular level to convert planar aryl luminophores having ACQ to AIEgens. Besides, the meso-pyrene BODIPY derivative shows excellent mechanofluorochromic behaviour.     

Fluorine Substitution Effects on Flexibility and Tunneling Pathways: The Rotational Spectrum of 2‐Fluorobenzylamine

The effect of ring fluorination on the structural and dynamical properties of the flexible model molecule 2‐fluorobenzylamine has been studied by rotational spectroscopy in free‐jet expansion and quantum chemical methods. The complete potential energy surface originating from the flexibility of the aminic side chain has been calculated at the B3LYP/6‐311++G** level of theory and the stable geometries were also characterized with MP2/6‐311++G**. The rotational spectra show the presence of two of the predicted four stable conformers: the global minimum (I), in which the side chain’s dihedral angle with the phenyl plane is almost perpendicular, is stabilized by an intramolecular hydrogen bond between the fluorine atom and one hydrogen of the aminic group; and a second conformer II (E_II?E_I≈5 kJ mol^?1) in which the dihedral angle is smaller and the amino group points towards the aromatic ortho hydrogen atom. This conformation is characterized by a tunneling motion between two equivalent positions of the amino group with respect to the phenyl plane, which splits the rotational transition. The ortho fluorination increases, with respect to benzylamine, the tunneling splitting of this motion by four orders of magnitude. The motion is analyzed with a one‐dimensional flexible model, which allows estimation of the energy barrier for the transition state as approximately 8.0 kJ mol^?1.