Mass spectral fragmentation patterns of heterocycles. IV . Tetracyclic phenothiazines. IX. Electron impact promoted mass spectral fragmentation of pyrrolo[3,2,1-kl]phenothiazine

The mass spectral fragmentation patterns of pyrrolo[3, 2, 1-kl]phenothiazine ( 1 ) and its 1, 10-dideuterioderi-vative [2] are reported. The site of deuterium substitution in 2 was established by examination of its ¹³C nuclear magnetic resonance spectrum. The heteroaromatic stability of 1 to electron impact is exemplified by the occurrence of the molecular ion as the base peak and the formation of a reasonably intense M²⁺ ion. An intense M-1 ion is also observed. The more abundant fragment ions appear to result from sulfur ionization. Fragment ions arising from ionization of the nitrogen constitute only a small fraction of the total ion current. Proposed fragmentation pathways of 1 are supported by the detection of appropriate metastable ions, exact mass measurements, and electron impact spectrum of 2 .     

Tetracyclic phenothiazines IV . Synthesis of 1,2,3,4-Tetrahydro-azepino [3,2,1-kl] phenothiazin -4-one

The synthesis of 1,2,3,4-tetrahydroazepine[3,2,1-kl]phenothiazin-4-one was accomplished by cyclization of phenothiazine-10-butanoic acid using phosphorus pentoxide and absolute ethanol. The title compound represents the first reported example of the azepino[3,2,1-kl]phenothiazine ring system. A vastly improved malonic ester-type synthesis of the precursor acid has also been developed.     

Tetracyclic phenothiazines V. Construction of the azepino[3,2,1-kl] -phenothiazine ring system by regioselective ring expansion

Solvolysis of 1,2-dihydro-3-hydroxy-3-(p-toluenesolfonyloxymethyl) 3H-pyrido[3,2,1-kl]-phenothiazine gave 1,2,3,4-tetrahydroazepino[3,2,1-kl]phenothiazin-3-one.     

Tetracyclic phenothiazines. III. . Intermolecular hydride transfer in acid induced disproportionation of 1,2-dihydro-3-hydroxy-3H-pyrido[3,2,1-kl] phenothiazines

1,2-Dihydro-3-hydroxy-3H-pyrido[3,2,1-kl]phenothiazines and 1H-pyrido[3,2,1-kl]phenothiazines undergo acid catalyzed disproportionation with intermolecular hydride transfer to form pyrido[3,2,1-kl]phenothiazinium salts and 1,2-dihydro-3H-pyrido[3,2,1-kl]phenothiazines. Sodium borohydride reduction of 3-alkyl- or 3-arylpyrido[3,2,1-kl]phenothiazinium salts gives 3-alkyl- or 3-aryl-1H-pyrido[3,2,1-kl]phenothiazines. In the presence of a proton source, borohydride reduction of pyrido[3,2,1-kl]phenothiazinium fluoroborate or 3-chloropyrido-[3,2,1-kl]phenothiazinium perchlorate gives 1,2-dihydro-3H-pyrido[3,2,1-kl]phenothiazine, while 1H-pyrido[3,2,1-kl]phenothiazine is formed in aprotic solvents with pyridine present.     

New tetracyclic ring systems. Synthesis of 1H-oxazolo[5,4,3-kl]phenothiazines and [1,4]oxazino[2,3,4-kl]phenothiazines

1-Hydroxyphenothiazine was converted to 1H-oxazolo[5,4,3-kl]phenothiazin-1-one, 1H-oxazolo[5,4,3-kl]-phenothiazine-1-thione,[1,4]oxazino[2,3,4-kl]phenothiazin-1(2H)one and [1,4]oxazino[2,3,4-kl]phenothiazine-1,2-dione. Also prepared from 1-hydroxyphenothiazine were the N-chloroacetyl derivative, the O-chloroacetyl derivative, the N,O-di(chloroacetyl) derivative and the sulfoxide.     

Preparation of pyrrolo[3,2,1-jk]carbazole by nickel(0) mediated ring contraction of pyrrolo[3,2,1-kl]phenothiazine. Proton NMR and mass spectral studies

Pyrrolo[3,2,1-jk]carbazole 1a , the previously unreported 16π-electron parent compound, has been synthesized by treatment of pyrrolo[3,2,1-kl]phenothiazine 2a with a 1:1 mixture of bis(1,5-cyclooctadiene) nickel(0) and 2,2′-bipyridyl. An unequivocal assignment of the ¹H nmr spectrum of 1a was made by decoupling experiments and by comparison with the ¹H nmr spectrum of 1,9-dideuteriopyrrolo[3,2,1-jk]carbazole 1b . Metastable ion studies, exact mass measurements and the dideuterioderivative 1b were utilized to investigate the electron impact induced fragmentation of 1a .     

Mass Spectral fragmentation patterns of heterocycles. V . Electron impact promoted mass spectral fragmentation of indolo[1,7-ab][1]benzazepine and Some of its Derivatives

The fragmentation patterns of 1,2,6,7-tetrahydroindolo[1,7-ab][l]benzazepin-1-one ( 1 ), 6,7-dihydroindolo-[1,7-ab][l]benzazepine ( 2 ) and indolo[1,7-ab][1]benzazepine ( 3 ) on electron impact have been examined. Loss of carbon monoxide to form the base peak at m/e 207 and loss of CHO radical to give m/e 206 consititute the major fragmentation pathways for 1. The moleclar ions ( M ⁺) are abundant for each of the compounds; observed as the second most intense peak for 1 (85% relative intensity) and the base peaks for 2 and 3 . The spectrum of 2 is characterized by intense M-1 and M-2 ions and by the presence of a M-15 ion (m/e 204) of moderate intensity (11.4%). In all other respects the spectra of 2 and 3 are strikingly similar. The M-15 ion from 2 , assigned the heteroaromatic pyrroloacridinium structure, is also formed in the spectrum of 1. A second heteroaromatic ion at m/e 191, common to the spectra of 1 , 2 and 3 , is believed to have the pyrrolocarbazol-ium structure. Metastable ion transitions and exact mass measurements support most of the proposed fragmentation pathways and structural assignments.     

On the synthesis of pyrido[3,2,1-kl]phenothiazine,quino[8,1-bc][1,4]benzothiazepine and their derivatives

This review article comprises tetracyclic rigid analogues of phenothiazine and dibenzothiazepine derivatives. In order to discover new useful drugs, the side chain of the heterocyclic nucleus is incorporated into a ring forming tetracyclic compounds. The text has been divided in thirteen sections.     

A synthesis of pyrrolo[ 3,2,1-kl] phenothiazine and derivatives

A synthesis of pyrrolo[3,2,1-kl]phenothiazine ( 1 ) is described. Electrophilic substitution of 1 leads to functionalization at the 2 position.     

Electron impact mass spectral interpretation for some thiophosphoryl-p-acetylaminobenzenesulfonamides

This work discusses the synthesis and the fragmentation patterns for 2-(p-acetylaminosulfonamido)-2-thiono-(5,5-dimethyl-1,3,2-dioxaphosphorinane)(1) and for the p-acetylaminosulfonylamides of O,O-diethylthiophosphoric acid (2), O,O-diphenylthiophosphoric acid (3), dimethylaminocyclohexylthiophosphoric acid (4), and diethylaminophenylthiophosphoric acid (5). A thionamidic-thiolimidic structure was attributed to compounds 1-5, consistent with their IR and NMR spectra. EI mass spectra at 70 eV, high resolution (HR) mass measurements and metastable ion spectra were used to elucidate the fragmentation processes and to determine the kinetic energy release values associated with the metastable ion dissociations. HR accurate mass measurements were used to confirm the compositions of the more abundant ions.     

Mass spectral fragmentation patterns of heterocycles. VII . Reinvestigation of fundamental processes in phenothiazines

Electron impact induced fragmentation patterns of simple phenothiazines have been reinvestigated using metastable ion studies, exact mass measurements and deuterated derivatives. Secondary fragmentation processes involving ions m/e 198, 171, 167, 166, 154, 140 and 139 have been clarified. Mechanisms for the release of sulfur (SH· and CSH·) nitrogen (HCN and H₂CN·) containing fragments from phenothiazine molecular ion are proposed based on the deuterium content of the daughter ions obtained from 1,9-dideutenophenothiazine. A revised mechanism for the expulsion of ketene from 10-acetylphenothiazine is suggested based on the fragmentation pattern of the 1,9-dideuterioderivative. The composition of m/e 140 was determined by high resolution measurement to be C₁₀H₆N and not C₁₁H₇ as previously reported.     

The reaction of 1,2-dioxo-1,2-dihydropyrrolo-[3,2,1-kl] phenothiazine with amines

The title compound I reacts with aliphatic amines producing ring-opened keto-amides of structure VII and with anilines forming imines of structure VIII.     

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.     

An efficient synthesis of the new benzo[c]pyrido[2,3,4-kl]acridine skeleton

A series of molecules of therapeutic interest, possessing the new skeleton of 1H-benzo[c]pyrido[2,3,4-kl]acridine with acyl or aminoacyl and methoxy or aminoalkoxy substituents on the aromatic homocycles were synthesized by means of a Friedl?nder-type reaction. The requisite 5-aminodihydroquinoline-4-ones 1, whose preparation is described, were reacted with the appropriate alpha-tetralones 2 using an acidic catalyst (PPTS) under azeotropic conditions. Optimized reaction time and yield depend on temperature, which must not be below 90 degrees C.     

Electron ionisation mass spectral analysis and fragmentation pathways for some thiophosphorylic p-carboxybenzene sulfonamides

The work presents the 70 eV electron impact mass spectra of some thiophosphorylic p-carboxybenzene sulfonamides, and proposes rationalisation of their fragmentation pathways. Accurate mass measurements of the fragment ions, and metastable ion analyses performed in the MIKES mode, were used to elucidate the most abundant ion compositions and to elucidate the fragmentation patterns of these pharmacologically interesting compounds.     

Electron impact fragmentation of some mixed cyclotetraphosphazenes

The electron impact fragmentations of some cyclotetraphosphazenes are reported and discussed. The major fragmentation path involves loss of two amine radicals and one chlorine radical in the series P₄N₄Cl_8-n(NMe₂)_n when n=2, and subsequent stages involve a ring contraction process with elimination of a P = N fragment, when n = 5 loss of amine radicals predominates on statistical grounds with little evidence of ring contraction. In the series P₄N₄F_8-n(NMe₂)_n fragmentation is dominated by loss of amino radicals when n = 4 and loss of fluorine radicals predominates on statistical grounds when n = 2. In the series P₄N₄F_8-nX_n (n = 2 or 4, X = Cl or Br), when n = 2 and X = Br the major fragmentation path is the loss of two bromine radicals, whereas when X = Cl the more favoured path is the loss of two chlorine radicals. In both, subsequent stages involve ring contraction reactions with elimination of a PN fragment. When n = 4 and X = Br or Cl on bond energy grounds the more favoured fragmentation pattern is the loss of bromine or chlorine radicals, respectively.     

Mass spectrometry in structural and stereochemical problems—CLXIV. Electron impact promoted fragmentation of some thiosemicarbazones

The mass spectral fragmentation of thiosemicarbazone derivatives of some typical aliphatic, alicyclic and aromatic aldehydes and ketones has been rationalized using high resolution mass spectrometry supplemented by deuterium labeling. Thiosemicarbazone derivatives of carbonyl compounds yield mass spectra which have little in common with those generated by their semicarbazone analogs.     

Reactivity of pyrido[4,3,2-kl]acridines: regioselective formation of 6-substituted derivatives

Pyrido[4,3,2-kl]acridines represent a new class of heterocycles, isomers of marine alkaloids. The 7H-pyrido[4,3,2-kl]acridine reacts as an electron rich heterocycle, and in particular via electrophilic substitution such as H/D exchange and the Vilsmeier-Haack reaction. The reaction is fully regioselective and gives the corresponding 6-substituted derivatives. The pyrido[4,3,2-kl]acridin-4-one reacts with amines and thiol, via 1,4-Michael addition to give the 6-amino or 6-thio analogues in a very efficient way. Molecular calculations account for the observed regioselectivity.