The stereochemistry of 2,4-disubstituted γ-butyrolactones and 2,4,6-trisubstituted-5,6-dihydro-4H-1, 3-oxazines

2,4-Disubstituted butyrolactones and 2,4,6-trisubstituted-5,6 dihydro-4H-1,3-oxazines show similar features in their ¹H and ¹³C- NMR spectra. Two geminal ring hydrogens of cis isomers give rise to a complex ABXY spectra when the substituent is alkyl or aryl. In spectra of trans isomers these patterns are degenerated. When R is OMe(in 4) or OCOMe (in 6) the difference in chemical shifts of geminal protons and vicinal coupling constants cannot be used for diagnosis. In ¹³C spectra ring carbons C-2 and C-3 in lactones and C-4 and C-5 in oxazine of trans isomers show a small but consistent shift to higher fields.     

Synthesis, 1H- and 13C-NMR spectra,crystal structure and ring openings of 1-methyl-6,9-epoxy-9-aryl-5,6,9,10-tetrahydro-1H-imidazo [3,2-e] [2H-1,5] oxazocinium methanesulfonate

The methanesulfonic acid catalyzed reaction of 1-(4-chloro- and 2,4-dichlorophenyl)-2-(1-methyl-2-imida-zolyl)ethanones 1a and 1b with glycerol produced cis- and trans-{2-haloaryl-2-[(1-methyl-2-imidazolyl)methyl]-4-hydroxymethyl}-1,3-dioxolanes 2a and 2b with a 2:1 cis/trans ratio. Besides these five-membered ketals, the reaction of 1a with glycerol afforded a small amount of trans-{2-(4-chlorophenyl)-2-[(1-methyl-2-imidazolyl)methyl]-5-hydroxy}-1,3-dioxane ( 3a , 7%). The reaction of methanesulfonyl chloride with cis-1 formed the corresponding methanesulfonates, cis- 4 , which rapidly cyclized to the title compounds 5 . Base-catalyzed ring opening of 5 furnished 1-methyl-5,6-dihydro-6-hydroxymethyl-8-(4-chloro- and 2,4-dichlorophenyl)-1H-imidazo[3,2-d][1,4]oxazepinium methanesulfonates 7 . Acid-catalyzed hydrolyses of 5 or 7 provided 1-methyl-2-[(4-chloro- and 2,4-dichloro)phenacyl]-3-[(2,3-dihydroxy)-1-propyl]imidazolium salts 12 . Structure proofs were based on extensive ¹H and ¹³C chemical shifts and coupling constants and structures of 3a and 5a were confirmed by single crystal X-ray crystallography.     

STEREOCHEMICAL PROPERTIES OF THE 1-CHLORO-1- PHENYL-2,5-DIMETHYL-2-PHOSPHOLENIUM ION AND DERIVED OXIDE AND PHOSPHINE

Abstract

The cycloaddition of phenylphosphonous dichloride and trans, trans-2,4-hexadiene, or the addition of chlorine to trans-1-phenyl-cis-2,5-dimethyl-3-phospholene, gave 1-chloro-1-phenyl-2,5-dimethyl-2-phospholenium chloride. This compound shows no evidence in its ³¹P and ¹H nmr spectra for the existence of cis, trans isomers, yet on hydrolysis or dehalogenation with magnesium the resulting oxide and phosphine, respectively, are seen to be isomer mixtures. This phenomenon is explained by a rapid equilibration of the cis, trans form of the I-chloro ion through a pentacovalent species. Structures of the oxides and phosphines were assigned by ¹H and ¹³C nmr relations. The 1-phenyl-cis-2,5-dimethyl-3-phospholenium ion and related compounds were also characterized.     

Multinuclear two-dimensional NMR: Assignments of natural abundance polypeptide 13C, 1H and 15N chemical shifts and demonstration of isomer interconversion

The polypeptide carbobenzoxy-glycyl-L -prolyl-L -leucyl-L -alanyl-L -proline (0.2 M in DMSO-d₆) was investigated using ¹³C, ¹H and ¹⁵N NMR in natural abundance at 4.7 tesla. The existence of cis–trans-Gly-Pro and -Ala-Pro bonds permits up to four isomers, and all four were observed (in a 60:30:7:3 ratio). ¹³C shifts of the proline β-CH₂ resonances are consistent only with the 60% form being trans–trans. The 30% form is either trans–cis or cis–trans (order as above) and was tentatively assigned as cis-trans on the basis of relaxation behavior. Refocused INEPT studies aided the ¹³C assignments. The ¹⁵N data were obtained using both NOE and INEPT excitation, with signals evident for the three major isomers. The spectra were analysed by starting from the ¹³C data, which were assigned based on known regularities in peptide spectra. A ¹³C? ¹H heteronuclear two-dimensional chemical shift correlation experiment allowed direct assignment of proton shifts for major and minor isomers. The NH proton shifts were assigned by running a homonuclear two-dimensional chemical shift correlation experiment and noting the correlation with the previously assigned α-CH protons. The ¹⁵N resonances were then assigned from a ¹⁵N? ¹H heteronuclear two-dimensional chemical shift correlation experiment, relating the ¹⁵N signals directly to the NH proton resonances. Isomer interconversion between the two major isomers was demonstrated by performing a magnetization transfer homonuclear 2D experiment. Off-diagonal intensity was noted relating the major and minor isomer alanine NH proton, as well as for the major and minor isomer leucine NH protons.     

Configurations and conformations of cis- and trans-N-methyl- and -N-benzyl-4,5- and -5,6-tetramethylenetetrahydro-1,3-oxazines

The configurations and conformations of cis- and trans-N-methyl- and -N-benzyl-4,5- and -5,6-tetramethylenetetrahydro-1,3-oxazines were determined by ¹H and ¹³C NMR spectroscopy. The cis isomers are conformationally homogeneous, having the hetero atom attached to the cyclohexyl ring, in the axial and equatorial positions, respectively, in the 5,6- and 4,5-tetramethylene compounds, similar to the case of the 2-p-nitrophenyl-substituted analogues investigated previously.     

Geometrical isomerism and 13C spectra of the β-substituted Enones R1?C(1)O?C(2)HC(3)H?R2

The ¹³C chemical shifts of the unsaturated carbons were measured in 31 cis and trans pairs of β-substituted enones R₁? C(1)O? C(2)H?C(3)H? R₂. In these polarized ethylenes the chemical shifts of the olefinic carbons are simply related by the equation δ_c=δ_t+A. The steric and electronic effects introduced by the R₁ and R₂ substituents influence the chemical shifts of C-2 and C-3 in both isomers. It is shown that the sign and magnitude of the intercept A mainly reflect the π-charge electronic density changes which arise in the cis isomer and are transmitted via the π-framework. The effect of the steric interaction on the chemical shift of C-3 in the cis isomers is postulated to be related to the symmetry of the substituents. Therefore, the differential shielding of C-3 is indicative of the conformational structure of the cis molecule.     

Stereoselective H2O eliminations in 3- and 4-arcylcyclohexanols under electron impact

The elimination of H20 from the molecular ions of trans-4- and trans-3-arylcyclohexanois takes place to a greater extent than in the corresponding cis isomers. The remarkable differences in abundance taken together with substituent effects and the results of deuterium labelling, show that configuration is retained in the molecular ions which undergo the elimination, and that this process is a cis-1,4 and cis-1,3 elimination in the trans-4- and trans-3- arylcyclohexanois, respectively. Possible mechanisms for the elimination in the cis isomers are discussed.     

1H and 13C NMR studies on 1,3,2-dioxarsolanes

The ¹H and ¹³C NMR spectra of a series of 1,3,2-dioxarsolanes have been obtained at 2.1 T and some at 9.4 T. The chemical shifts and spin-spin coupling constants have been obtained from complete spectral analyses of the ¹H and proton-coupled ¹³C spectra. The spectral data are interpreted on the basis of two rapidly interconverting half-chair conformers with a pseudoaxial substituent at arsenic. Unique assignment of syn/anti or cis/trans geometries have been made from ¹H or ¹³C NMR spectroscopy alone. The syn and trans isomers of the 4-methyl- and 4,5-dimethyl-1,3,2-dioxarsolanes, respectively, appear to be conformationally biased towards the forms with pseudoequatorial methyl groups. The general trends in the geminal and vicinal ¹H? ¹H and ¹³C? ¹H coupling constants are interpreted in terms of stereospecific, electronegativity and lone-pair effects of the oxygen heteroatoms and conformational factors. The NMR data on the 1,3,2-dioxarsolanes are discussed with reference to related 1,3-dithoxa- and 1,3-dithia- five-membered rings with As, P, S or C at the 2-position.     

Saturated heterocycles, 248. Synthesis of 2,4-dioxo and 4-oxo-2-thioxo derivatives of octahydrocyclopenta[d]pyrimidines

Unsubstituted and 1-benzyl-substituted cis-cyclopenta[d]pyrirnidine-2,4-diones and cis-2-thioxo-cyclopenta[d]pyrimidin-4-ones 9a,b and 10a,b were prepared from the corresponding cis-2-amino-1-cyclopentanecarboxylates 3 and 5 with potassium cyanate and thiocyanate. It was found that the cis derivatives 7a-h readily underwent ring closure, resulting in 3-substituted cis-2,4-cyclopenta[d]pyrimidinediones and cis-2-thioxocyclopenta[d]pyrimidin-4-ones 11a-d and 12a-d , whereas the trans counterparts 8a-d failed to cyclize, but gave hydrolysed amino acid derivatives 13a,b and 14 . This difference in the reactivities of the cis and trans isomers is a further example of the difficulty of preparing cyclopentane trans-fused six-membered 1,3-heterocycles by ring closure.     

Ketalizations of aryl ω-(2-imidazolyl)alkyl ketones by glycerol and 3-mercapto-1,2-propanediol. synthesis and characterization of cis- and trans-{2-aryl-2-[ω-(2-imidazolyl)alkyl](1,3-dioxolan-4-yl and 1,3-oxathiolan-5-yl)}methanols

Aryl 2-[(2-imidazolyl)ethyl or 3-(2-imidazolyl)propyl]ketones were ketalized by glycerol or 3-mercapto-1,2-propanediol in boiling benzene in the presence of 4-toluenesulfonic acid to provide the title compounds. The aryl substituents are 4-chloro-, 4-bromo-, 4-fluoro-, or 2,4-dichlorophenyl. While aryl (2-imidazolyl)methyl ketones condensed with glycerol to form cis- and trans-{2-aryl-2-[(2-imidazolyl)methyl]-4-(hydroxymethyl)}-1,3-dioxolanes, related condensations with 3-mercapto-1,2-propanediol, under similar, or even more stringent reaction conditions, produced no 1,3-oxathiolane analogs, with the starting ketones being recovered. Separation and structure determination of these racemic cis and trans isomeric products are described. The structure of these stereoisomers was established by means of ¹H and ¹³C nmr correlation and nOe experiments. Selective methylation of the N-unsubstituted 2-imidazolyl alcohols with one equivalent sodium hydride and methyl iodide provided the corresponding N-methyl alcohols in excellent yields. With excess benzoyl chloride, N-unsubstituted 2-imidazolyl alcohols were initially converted to O, N-dibenzoates from which the N-benzoyl group was easily cleaved by ammonium hydroxide in ethanol to provide benzoate esters.     

NMR experiments on acetals—XXXIX: Conformational insights through NMR studies at 300 MHz of 2-methyl-4-halogenomethyl-1,3-dioxolanes

NMR spectra of cis- and trans-2-methyl-4-halogeno-methyl-1,3-dioxolanes have been analysed at 300 MHz. Some of the extracted parameters facilitate easy distinction between these 1,3-dioxolanes and the corresponding structurally isomeric 2-Methyl-5-halogeno-1,3-dioxanes. Criteria enabling configurational assignments to be made for the cis-trans isomers of the dioxolane series are tested. The Me-2 group causes an upfield shift (0·2 to 0·3 ppm) of a trans proton at position 5, but the reversed shift for the corresponding cis proton. This competes with, or even overwhelms the effect of the CH₂X-4 substituent, which by virtue of its pronounced preferential rotameric orientation and in comparison with a simple Me-group, has no large upfield effect on the shift of the syn-adjacent proton. Shift criteria and coupling constants J_{H-4, H-5} in cis- and trans derivatives allow further conformational insights into these 1,3-dioxolanes.     

Stereochemistry of alkyl 3-substituted 4-halotetrahydro-2-oxo-3-furancarboxylates: 2—1H and 13C NMR spectra

The ¹H NMR parameters of methyl 3-substituted cis-4-halotetrahydro-2-oxo-3-furancarboxylates are reported, with assignments of the ring protons based on solvent-induced changes in the vicinal trans coupling constants, ³J(H-4, H-5). Preferred conformations, ce with a pseudo-equatorial halogen for the cis isomers and ta with a pseudo-axial halogen for the trans isomers, have been suggested on comparison of the magnitudes of J(trans) and J(gem) in both series. The ³J(¹³CH₃, H-4) values measured for methyl cis-4-bromotetrahydro-3-methyl-3-furancarboxylate, methyl trans-4-bromotetrahydro-3-methyl-3-furancarboxylate and trans-3,4-dibromodihydro-3-methyl-2(3H)-furanone have confirmed the stereochemical assignments.     

Isolation by HPLC. and Identification by NMR. Spectroscopy of 11 mono-, di- and tri-cis isomers of an aromatic analogue of retinoic acid,ethyl all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6, 8-tetraenoate

Photoisomerization of an aromatic analogue of retinoic acid, ethyl all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6, 8-tetraenoate 1 in dilute solutions of hexane, benzene, and ethanol yielded multi-component mixtures of cis isomers which were separated by HPLC. FT-¹H-NMR. at 270 MHz and, in some cases, homonuclear decoupling and Overhauser experiments as well as ¹³C-NMR. were applied to establish the structures of 4 mono-cis, 4 (of 6 possible) di-cis, and 3 (of 4 possible) tri-cis isomers. The structures of 3 isomeric esters, namely (2Z, 4E, 6E, 8E) 6 , (2Z, 4Z, 6E, 8E) 9 , and (2Z, 4Z, 6Z, 8E) 7 were independently confirmed by direct syntheses. The ¹H-NMR. data of all these compounds and the ¹³C-NMR. data of the all-trans and of 6 cis isomers available in sufficiently large quantities are discussed.     

Stereochemical studies, 73. Saturated heterocycles, 60

N-Substituted-2-carboxamido-1-cycloalkanols were cyclized with 1,1-carbonyldiimidazole to synthesizecis- andtrans-N-alkyl-,N-aralkyl- andN-aryl-2,4-dioxo tri- and tetramethyleneperhydro-1,3-oxazines. The structures of the compounds and theircis ortrans ring anellation were confirmed by IR,¹H- and¹³C-NMR spectroscopy, and thecis andtrans pairs of isomers were compared to establish the predominant conformation of the flexiblecis isomers. It was found that—similarly to the 1,3-oxazin-2- and -4-ones studied earlier—the O-endo conformers are preferred, in which the 1-oxygen atom isaxial to the alicyclic ring; this is independent of the number of ring atoms in the alicycle, and of the presence of an oxazinedione ring, even though this is more flexible that the ring of oxazinones.

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Synthese und Konformation voncis undtrans 2-substituierten kondensierten 1,3-Oxazin-2,4-dionen

Zusammenfassung cis- undtrans-N-Alkyl-,N-Aralkyl- undN-Aryl-2,4-dioxo-, tri- und tetramethylen-perhydro-1,3-oxazine wurden aus 2-Carboxamido-1-cycloalkanolen und 1,1-Carbonyldiimidazol dargestellt. Mit Hilfe der IR,¹H- und¹³C-NMR Spektroskopie wurden die Struktur, diecis- odertrans-Annellierung der Ringe und die bevorzugte Konformation der flexiblencis-Isomeren im Vergleich zumcis-trans Isomerenpaar nachgewiesen. Ähnlich zu den früher untersuchten 1,3-Oxazine-2- und -4-onen ist hier ebenfalls das O-endo Konformere bevorzugt; in diesem ist der Sauerstoffaxial angeordnet, und zwar unabhängig von der Zahl der alicyklischen Ringatome und dem flexibleren Oxazindionring.

     

Kinetics of the reactions of O3 and OH radicals with a series of dialkenes and trialkenes at 294 ± 2 K

Rate constants for the gas phase reactions of O₃ and OH radicals with 1,3-cycloheptadiene, 1,3,5-cycloheptatriene, and cis- and trans-1,3,5-hexatriene and also of O₃ with cis-2,trans-4-hexadiene and trans -2,trans -4-hexadiene have been determined at 294 ± 2 K. The rate constants determined for reaction with O₃ were (in cm³ molecule^-1s^?1 units): 1,3-cycloheptadiene, (1.56 ± 0.21) × 10^-16; 1,3,5-cycloheptatriene, (5.39 ± 0.78) × 10^?17; 1,3,5-hexatriene, (2.62 ± 0.34) × 10^?17; cis?2,trans-4-hexadiene, (3.14 ± 0.34) × 10^?16; and trans ?2, trans -4-hexadiene, (3.74 ± 0.61) × 10^?16; with the cis- and trans-1,3,5-hexatriene isomers reacting with essentially identical rate constants. The rate constants determined for reaction with OH radicals were (in cm³ molecule^?1 s^?1 units): 1,3-cycloheptadiene, (1.31 ± 0.04) × 10^?10; 1,3,5-cycloheptatriene, (9.12 × 0.23) × 10^?11; cis-1,3,5-hexatriene, (1.04 ± 0.07) × 10^?10; and trans 1,3,5-hexatriene, (1.04 ± 0.17) × 10^?10. These data, which are the first reported values for these di- and tri-alkenes, are discussed in the context of previously determined O₃ and OH radical rate constants for alkenes and cycloalkenes.     

Reactions of 3-amino-1-phenyl- and 3-amino-1-(thien-2-yl)-4,4,4-trifluorobut-2-en-1-ones with 1,2-diaminopropane and 1,2-diamino-3,3,3-trifluoropropane

The reactions of 3-amino-1-phenyl-and 3-amino-1-(thien-2-yl)-4,4,4-trifluorobut-2-en-1-ones with 1,2-diaminopropane under kinetically controlled conditions afford mixtures ofcis andtrans isomers of 2-aroylmethyl-4-methyl-2-trifluoromethylimidazolidines. Analogous reactions with 1,2-diamino-3,3,3-trifluoropropane yieldcis-2-aroylmethyl-2,4-bis(trifluoro-methyl)imidazolidines. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2135–2139, November, 1999.     

Compounds with bridgehead nitrogen. 44—the conformational analysis of perhydropyrido[1,2-c] [1,3]thiazine

The 270 MHz NMR data on trans- and cis-(H-4a, H-7)-7-ethylperhydropyrido[1,2-c][1,3]thiazine show heavy conformational bias to the trans- and S-inside cis-fused conformations, respectively. Comparison of the ¹³C NMR spectra of these anancomeric systems with the ¹³C NMR spectrum of perhydropyrido[1,2-c][1,3]thiazine indicates a trans-?S-inside cis-conformational equilibrium for the latter compound in CDCl₃ at 25°C, containing ca 75% trans-fused conformer. The ¹³C NMR spectrum of perhydropyrido[1,2-c][1,3]-thiazine at ?75°C showed 64% trans-fused conformer and 36% S-inside cis-conformer.     

Effect of allylic strain on the conformations of diphenyl-substituted tetrahydro-1,3-oxazin-2-ones and hexahydropyrimidin-2-ones

The conformations of the cis and trans isomers of 4,6-diphenyl-, 4,5-diphenyl- and 5,6-diphenyltetrahydro-1,3-oxazin-2-one and 4,5-diphenylhexahydropyrimidin-2-one, and of some of their N-substituted derivatives, have been studied by ¹H NMR. Conformers with 4a, 6e-, 4a, 5e- and 5a, 6e-phenyl groups are preferred in the respective isomers of the N-H oxazinones, confirming a half-chair conformation of the ring. Allylic strain caused by N-substituents shifts strongly the a,e?e, a equilibria in trans-4,6-diphenyl- and cis-4,5-diphenyl-oxazinones, but only moderately the e,e?a,a equilibria in the compounds with trans-vicinal phenyl groups. In the latter, the diaxial conformation is preferred only in the case of bulky N-substituents. The diaxial conformation is more favoured in the trans-4,5-diphenylpyrimidones.     

Stereochemical characterization of some mono- and diaryl substituted ethylene oxides by NMR spectroscopy

NMR spectra of several styrene, stilbene and stilbazole oxides have been determined, and chemical shifts and coupling constants have been correlated with cis-and trans-configurations. Assignments have been made for all protons, and double resonance technique and ¹³C? H coupling constants have been used in some particular cases. An explanation is proposed for the observation that chemical shifts of oxirane protons are higher for cis than for trans isomers.     

Stereostructure of condensed-skeleton cis- and trans-dihydro-1,3-thiazines and 1-thia-3-azaspiroalkenes

The stereostructures of some condensed-skeleton cis- and trans-dihydro-1,3-thiazines and 1-thia-2-phenyl-3-azaspiro[4n + 1]alk-2-enes (n = 3–6) were established by ¹H and ¹³C NMR spectroscopy. A comparative study indicated that the cis-thiazines have greater conformational mobility than the corresponding oxazines, although the preferred conformer of the two types of cis compounds is the same, with the sulphur axial and the 4-methylene group equatorial relative to the rings.