Mass spectrometry in structural and stereochemical problems—CCXLIV : The influence of substituents and stereochemistry on the mass spectral fragmentation of progesterone

The complete high resolution mass spectra of progesterone (Δ⁴-pregnene-3,20-dione) and twenty-nine stereoisomers and alkyl substituted analogs have been analyzed with the aid of the recently developed computer program INTSUM. Progesterone analogs with “normal” configuration at the six chiral skeletal carbon atoms give rise to abundant ions corresponding to cleavage of the 1–2 and 3–4 bonds (ketene elimination), to cleavage of the 6–7 and 9–10 bonds (ring B cleavage), and to cleavage of the 13–17 and 15–16 bonds (partial ring D cleavage); these reactions are frequently followed by elimination of alkyl radicals. Alkyl groups at C-6 and C-10 exert a pronounced influence on the formation and fragmentation of the [M-ketene] ions. Reversal of configuration at C-10 increases the importance of ring B cleavage, whereas reversal at C-17 favors the partial cleavage of ring D. The fragmentation of 17-alkylprogesterones differs significantly from the general pattern, with acetyl loss (cleavage of the 17–20 bond) and partial ring D cleavage as the predominating reactions. Loss of ring D by cleavage of the 13–17 and 14–15 bonds is not an important reaction of progesterones. Direct interaction of the two ketonic functions was not observed.     

Substituent effects on the ring opening of 2-aziridinylmethyl radicals

[reaction: see text] Substituent effects on the ring-opening reactions of 2-aziridinylmethyl radicals were studied systematically for the first time utilizing the ONIOM(QCISD(T)/6-311+G(2d,2p):B3LYP/6-311+G(3df,2p)) method. It was found that various substituents on the nitrogen atom had a relatively small effect on the ring opening of the 2-aziridinylmethyl radical. A pi-acceptor substituent at the C(1) position reduced the energy barrier for C-C cleavage dramatically, but it increased the energy barrier for C-N cleavage significantly at the same time. When the C(1) substituent is alkyl, the ring opening should always strongly favor the C-N cleavage pathway, regardless of whether the N substituent is alkyl, aryl, or COR. When the C(1) substituent is CHO (or CO-alkyl, CO-aryl, or CO-OR but not CO-NR(2)), the ring opening strongly favors the C-C cleavage pathway, regardless of whether the N substituent is alkyl, aryl, or COR. When the C(1) substituent is aryl (or alkenyl or alkynyl), the ring opening should favor the C-C cleavage pathway if the N substituent is alkyl or COR. If both the C(1) substituent and the N substituent are aryl, the ring opening should proceed via both the C-C and C-N cleavage pathways. The solvent effect on the regioselectivity of the ring opening of the 2-aziridinylmethyl radicals was found to be very small. The substituent effects on C-C cleavage could be explained successfully by the spin-delocalization mechanism. For the substituent effects on C-N cleavage, an extraordinary through-bond pi-acceptor effect must be taken into account. Furthermore, studies on bicyclic 2-aziridinylmethyl radicals showed that the ring strain could also affect the regiochemistry of the ring-opening reactions.     

Photosensitized oxygenation of cyclic sulfides. Selective C-S bond cleavage

TPP-Sensitized photooxidation of five-membered ring sulfides in aprotic solvent afforded C-S bond cleavage products, unlike six- and seven-membered ring sulfides which gave only S-oxidation products. The products as well as substitution and concentration effects suggest that C-S bond cleavage depends upon acidity of α-proton of persulfoxide intermediate.     

Studies on a Simple Route to a Bicyclic Reserpine Intermediate

A concise route is described to a Reserpine synthetic intermediate having the features of ring E and an oxygen function for constructing ring D. This involves an unusual α-diketone cleavage, the selective elaboration of the carboxylated ring in 1-naphthoic acids and selective boron halide cleavage of ester and ether groups.     

The electron impact-induced fragmentation of 2-arylthiazoles

The mass spectrometric fragmentation of 2-aryl thiazoles centres, like that of simple thiazoles, around the cleavage of the 1,2 and 3,4 bonds of the thiazole ring. One characteristic species does arise from the fission of the 1,5 and 2,3 bonds, viz. a thiobenzoyl ion. The fragmentations of some substituents at the 4 and 5 positions of the thiazole ring, prior to ring cleavage, are also described.     

Intramolecular single and double hydrogen migrations in the mass spectra of substituted tetrahydro-1,3,2-oxazaphosphorin-2-oxides

The mass spectral fragmentation of substituted tetrahydro-1,3,2-oxazaphosphorin-2-oxides occurs by the cleavage of ring bonds. The ions due to simple cleavage, single and double hydrogen migration, seem to be triggered by C O bond cleavage of the oxazaphosphorin ring. The variations in the relative abundance of ions arising due to similar fragmentation modes have been found to depend on the nature of the substituent and the stability of the particular fragment. The single hydrogen transfer process is supported by metastable ion and shift techniques.     

Ring cleavage reactions of 3- and 5-non-substituted isoxazoles

5-Methylisoxazoles with electron-accepting groups at C-4 (1a-c) and 2,3-dimethylisoxazolium iodide (II) undergo ring cleavage when treated with organic bases. The nature of the open chain products which were obtained (stable enolates, β-diketones, esters) depends on the group at C-4 and the strength of the base. In some of these processes aromatic aldehydes were used in order to determine the competition between the condensation and the cleavage reaction. The mechanism of the nucleophilic ring cleavage of II is also shown.     

Photocatalytic Ring Opening of α-Epoxyketones: 1,3-Dioxolane Formation

 Photocatalytic ring opening of α-epoxyketones by 2,4,6-triphenylpyrylium tetrafluoroborate in acetone resulted in the formation of 1,3-dioxolanes as major products through C–O bond cleavage and the formation of alcoholic by-products through C–C bond cleavage. The type and nature of the substituent affects the rate of ring opening.     

Ring Cleavage of N-Alkylisothiazolilm Salts by Complex Metal Hydrides. Synthesis of β-Enaminothioketones

N-Alkylisothiazolium salts undergo ring cleavage when treated with complex metal hydrides to give β-enami-nothioketones in high yields.

The isothiazole nucleus is remarkably stable to chemical attack by reducing agents.¹ In fact, little work has been published on reactions involving reductive cleavage of the isothiazole ring. Thus, other azole systems as isoxazole are readily cleaved by catalytic hydrogenolysis whereas the isothiazole nucleus, in the same conditions, remains unchanged.² However there are instances in which ring cleavage occurs. For example, cleavage of isothiazole during lithiation at the 5-position gives a small proportion of a β-mercaptoenone resulting from the cleavage of the N-S bond.^3,4 Isothiazoles are reductively desulfu-rized by Raney nickel and this method has been used by Woodward in a remarkable synthesis of colchicine.⁵     

Studies on the synthesis of heterocyclic compounds. XIV. Cleavage of 1,3-benzoxathioles by magnesium bromide-acetic anhydride

The cleavage reaction of some 1,3-benzoxathioles with magnesium bromide and acetic anhydride has been studied. In all the 1,3-benzoxathioles studied, the opening of the heterocyclic ring occurs first with cleavage of the C O bond and formation of bromides and their corresponding products of hydrolysis. Successively also the cleavage of the C S bond can occur. The competitive electrophilic substitution on the benzene ring becomes appreciable only in the 1,3-benzoxathioles-2,2-disubstituted with sterically demanding groups. The structure of newly prepared compounds has been determined by analytical and spectroscopic data and when possible by comparison with authentic samples.     

Pyrolysis and mass spectra of trimethylsilyl derivatives of monosaccharides

The pyrolysis of trimethylsilyl derivatives of saccharides (1) was investigated by DTA-TG, MS, GC/MS and TG-GC/MS. The DTA-TG/DTG curves showed that the pyrolysis of 1 occurred in one stage. The exothermic peaks were due to sublimation or thermal decomposition by vaporization. The cleavage mechanism by electron impact of 1 was classified into four categories: 1) stepwise elimination of the side-chain, 2) cleavage of the side-chain, 3) cleavage of the pyranose ring, and 4) cleavage of the pyranose ring and side-chain at the same time. The mass-spectrum for 1 revealed the main common four fragment ions, such asm/z 73, 191, 204 and 217, with cleavage of the pyranose ring. These fragment ions were detected with a similar retention time in the gas cromatogram by GC/MS or TG-GC/MS. The retention time for 1 increased in the sequence aldopentose相似文献   

Asymmetric ring cleavage reaction with a combination of optically active cycloalkane-1,2-diol and Lewis acid: application to formal synthesis of (−)-alloyohimbane and approach to construction of adjacent chiral quaternary centers

Asymmetric ring cleavage reaction of meso-carbobicyclic ketones by a combination of benzaldehyde, chiral cycloalkane-1,2-diol, and Lewis acid gave optically active styrenyl esters of 26-69% ee in moderate yield. The ring cleavage reaction could be applied to the construction of adjacent chiral quaternary carbons, and also to the formal synthesis of natural alkaloid (−)-alloyohimbane.     

The effect of fluorine substitution on the structure of oxiranes and on the energetics of the oxiranylcarbinyl radical ring opening

Fluorine substituent effects on the structure of oxirane and on the kinetic behavior of oxiranylcarbinyl radicals, as determined by DFT calculations, have been found to be similar to those observed for the analogous fluorinated cyclopropylcarbinyl radical systems. A structural and energetic analysis showed that a stereoelectronic effect involving preferential interaction of the semi-occupied atomic orbital of the radical with the weaker ring bond is the major factor that contributes to the regiochemistry of the ring opening of fluorinated oxiranylcarbinyl radicals. With low and potentially zero activation barriers, 3,3-difluorooxiranylcarbinyl radical and cation undergo ring opening with CO bond cleavage and CC cleavage, respectively.     

Alkyl C-O ring cleavage of bicyclic beta-lactones with Normant reagents: synthesis of a Merck IND intermediate

Highly diastereoselective Cu(I)-mediated, bicyclic beta-lactone ring cleavage reactions with either alkyl or aryl cuprates proceeded with inversion of stereochemistry to give optically active trans-substituted cyclopentanes and cyclohexanes. Optimization of typically problematic aryl cuprate additions was made possible by minimization of a competing bromide-induced ring cleavage process. The utility of this process was demonstrated by an efficient synthesis of a Merck investigational new drug (IND) intermediate for an anti-HIV CCR5 antagonist.     

Mass spectra of chloro-, aminochloro- and ethylaminochloro-s-triazines

The mass spectra of cyanuric chloride and all of the possible amino-and ethylaminochloro-s-triazines have been investigated. The simpler compounds provide evidence for the structures of low mass fragment ions found in the spectra of the more complex derivatives. Fragmentation patterns are presented which account for most of the major ions. These pathways involve either the initial loss of a chlorine atom (important for the simple aminochlorotriazines) or ring cleavage with expulsion of cyanogen chloride (important for cyanuric chloride). The ethyl derivatives undergo cleavage of the side chain prior to either ring cleavage or chlorine expulsion.     

Photolysis of 1-alkylcycloalkanols in the presence of (diacetoxyiodo)benzene and I2. Intramolecular selectivity in the beta-scission reactions of the intermediate 1-alkylcycloalkoxyl radicals

The C-C beta-scission reactions of 1-alkylcycloalkoxyl radicals, generated photochemically by visible light irradiation of CH2Cl2 solutions containing the parent 1-alkylcycloalkanols, (diacetoxy)iodobenzene (DIB), and I2, have been investigated through the analysis of the reaction products. The 1-alkylcycloalkoxyl radicals undergo competition between ring opening and C-alkyl bond cleavage as a function of ring size and of the nature of the alkyl substituent. With the 1-propylcycloheptoxyl, 1-propylcyclooctoxyl,and 1-phenylcyclooctoxyl radicals, formation of products deriving from an intramolecular 1,5-hydrogen atom abstraction reaction from the cycloalkane ring has also been observed. The results are discussed in terms of release of ring strain associated to ring opening, stability of the alkyl radical formed by C-alkyl cleavage, and with cycloheptoxyl and cyclooctoxyl radicals, also in terms of the possibility of achieving a favorable geometry for intramolecular hydrogen atom abstraction.     

Enantioselective total synthesis of (-)-heliannuol A

An efficient and enantiocontrolled total synthesis of (-)-heliannuol A has been accomplished by employing ring closing metathesis and sequential diastereoselective epoxidation and regioselective reductive cleavage of the epoxide ring.     

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS XXX. MASS SPECTROSCOPIC INVESTIGATION OF 2-ALKYL-2-OXO-1,3,2-DIOXA-PHOSPHORINANE AND-PHOSPHEPANE

Abstract

The mass spectra of 2-alkyl-2-oxo-1,3,2-dioxa-phosphorinane and-phosphepane showed that the ring opening was in competition with the cleavage of the P[sbnd]C bond. According to the fragmentation pathway, which was dependent on the structure of exocyclic substituents on phosphorus, the 2-alkyl-2-oxo-1,3,2-di-oxa-phosphorinanes can be classified in two categories. The main process in category A was the ring opening and/or C[sbnd]C bond cleavage. While in category B the cleavage of P[sbnd]C bond was predominant. However, for 2-alkyl-2-oxo-1,3,2-dioxa-phosphepane. no matter how the structure of 2-alkyl group was, the ring opening was a dominant process.     

The mass spectrum of 1-(2-thienyl) hexane-1-13C

The mass spectrum of 1-(2-thienyl) hexane-1-¹³C is reported. The principal fragmentation routes ofthe parent ion are delineated. Beta cleavage of the alkyl chain predominates, and the label retention indicates that the alpha carbon atom remains with the charged ring moiety. A substantial part of the m/e 97 ion undergoes a ring expansion to a six membered ring. A small amount of alpha cleavage of the alkyl chain occurs with the expected loss of the label. Further fragmentation of the ions from initial alpha or beta cleavage produces similar fragment ions. It is noted that many of the neutral particles lost in the formation of the fragment ions are typical of those encountered in the alkylbenzenes or other aromatic ion systems.     

Electron impact induced fragmentations of some 2,2-disubstituted 1,3-oxathiolanes

The electron impact induced fragmentations of nine 2,2-disubstituted 1,3-oxathiolanes have been studied by means of exact mass measurement and metastable ion analysis. The ring cleavage almost always takes place so that the C(2)? S and C(5)? O bonds are broken, leading to the most stable products. The nature of the substituents determines the primary fragmentations of molecular ions. Ring cleavage is important only if both substituents are alkyl groups or if the carbon attaching to the ring has an alkyl character. The loss of the substituent becomes the most favourable process if it is attached to the ring through the electron-deficient carbon atom.