Free‐radical 4‐nitrophenylation of thieno[2,3‐b]pyridine. Part 3: Consideration of mechanistic and selectivity factors involved in the substitution process

A 1:1 geometrically oriented encounter complex between thieno[2,3‐b]pyridine (1) and 4‐nitrophenyldia‐zoacetate (2) is proposed to account for the dominant formation (ca. 64%) of the 2‐isomer in the mixture of 4‐nitrophenyl‐l isomers obtained previously. A mechanism involving one‐electron transfer from 1 to 2 plus fragmentation of 2· into 4‐nitrophenyl free radical, N₂, and acetate ion is invoked. Formation of other isomers is discussed. It is noted that there is a close correlation between orientational rules plus mechanisms of reaction for numerous free‐radical substitutions (S_R) with S_N reactions of alkyllithiums on furan, thiophene, N‐alkylpyrroles, pyridine, and their condensed aromatic molecules, including 1, as substrates. Also isomeric selectivities for S_E, S_N, and S_R substitutions into 1 were shown to be qualitatively consistent with one another. While S_E reactions occur largely at position 3 and then at 2, S_N and S_R reactions occur either at 2 or 6. Selectivity for positions 4 or 5 is small or zero.     

PMR studies of N-substituted-2,5-dimethyl-4-piperidones

PMR characteristics of some isomeric 1-substituted-2,5-dimethyl-4-piperidones are reported and major isomers shown to have a trans 2,5-dimethyl configuration. Differences between benzylic methylene signals of isomeric 1-benzyl analogs provide evidence of the preferred conformation of the cis derivative. Evidence of the D/H exchange of α-protons in 1,2,5-trimethyl-4-piperidone base and of addition of D₂O to the carbonyl group of the corresponding hydrochloride and methiodide salts is also demonstrated. The effect of a 2-methyl substituent upon the chemical shifts of N-methyl groups in some piperidine methiodides is discussed.     

Determination of the threo- and erythro- configurations of vicinal diastereomeric derivatives of higher fatty acids with the aid of PMR spectra

Conclusions The PMR spectra of vicinal diastereomeric dihydroxy-, acetoxyhydroxy-, and halohydroxyoctadecanoic and -docosanoic acids and their trimethylsilyl derivatives have been considered. It has been shown that the signals of the methine protons of the erythro isomers appear at lower fields than those of the threo isomers. On passing from the dihydroxy, acetoxyhydroxy, and halohydroxy acids to their TMS derivatives, the signal of the methine proton shifts down-field, and = CHOSi (CH₃)₃ — CHOH is greater for the threo form than for the erythro form, The difference in the chemical shifts of the vicinal methine protons of the dihydroxy, acetoxyhydroxy, and halohydroxy acids and their TMS derivatives can be used to determine the threo and erythro configurations of the corresponding diastereometric derivatives of higher fatty acids.A. A. Zhdanov Leningrad State University. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 299–305, May–June, 1978.     

Improved procedures for the synthesis of (S)-2-[N-(N′-benzylprolyl)amino]benzophenone (BPB) and Ni(II) complexes of Schiff's bases derived from BPB and amino acids

(S)-N-Benzylproline (BP) was obtained by the reaction of (S)-proline and benzylchloride in high chemical yield (89%). (S)-2-[N-(N′-Benzylprolyl)amino]benzophenone (BPB) was synthesized in amounts greater than 100 g by the SOCl₂ promoted condensation of BP with 2-aminobenzophenone (yield 82%). Ni(II) complexes of Schiff's bases derived from BPB and amino acids were prepared by an improved procedure involving the use of KOH as a base and MeOH as solvent (yield 90–91%).     

Diastereoselectivity of the mercuration of acyclic allylic alcohols

The diastereoselectivity of the mercuration of acyclic alkenes $\text{4}$ can be reversed by changing the substituent in the allylic position; with alcohols the erythro isomers $\text{5}$ and with esters or hemiacetals the threo isomers $\text{6}$ and $\text{8}$ are formed predominantly (Table I).     

Dithiazoliumsalze mit Halometallaten – Synthese und Struktur von 3-Diethylamino-5-phenyl-1,2,4-dithiazolium-tetrachloro-niccolat(II)

Dithiazolium Salts of Halometalates – Synthesis and Structure of 3-Diethylamino-5-phenyl-1,2,4-dithiazolium-tetrachloroniccolate (II ) Chlorination of Ni^II-coordinated 1,1-diethyl-3-benzoyl-thiourea by SOCl₂ in acetonitrile yields turquoise 3-diethyl-amino-5-phenyl-1,2,4-dithiazolium-tetrachloroniccolate. Its reduction produces cis-bis-(1,1-diethyl-3-thiobenzoylthioureato)nickel(II). The mechanism of formation as well as the crystal and molecular structure of the title compound are presented.     

(+)-樟脑亚甲胺α位负碳离子的不对称氧化偶联反应研究

本文研究了(+)-樟脑亚甲胺α位负碳离子的氧化偶联反应, 所得偶联产物经高效液相色谱分析,测定了苏式赤式比,苏式异构体的de.值由^1HNMR测定为20-95%,对影响偶联反应的诸因素:如氧化偶联剂.溶剂.碱等进行了初探.     

Monofluoration quantitative par le phenyltetrafluorophosphorane influence de la température

The monofluorination by substitution of the hydroxyl group of the β-hydroxyesters of (o, m, p) Z - C₆H₄ - C(OH)R - CH R′ - COOR″ structure (where Z = halogen, methyl, methoxy, nitro and H) of 2,2,2 trichloroarylcarbinols by the phenyl tetrafluorophosphorane is described. The temperature at which the alkoxytrifluorophosphorane is decomposed, determines the nature (alkene alkoxytrifluorophosphorane, monofluorinated compounds) of the products and their yield. Knowledge of this temperature for erythro and threo isomers permits the selective fluorination of one them in a mixture.     

Beiträge zur Chemie des Phosphors. 136 [1]. 31P-Kernresonanzspektren und Struktur der 1,3-Dihalogen-1,2,3-tri-tert-butyltriphosphane X(t-BuP)3X,X = Cl,Br, I

Contributions to the Chemistry of Phosphorus. 136. ³¹P-N.M.R. Spectra and Structure of 1,3-Dihalogen-1,2,3-tri-tert-butyltriphosphanes X(t-BuP)₃X, X = Cl, Br, I The 1,3-dihalogen-1,2,3-tri-tert-butyltriphosphanes (t-BuP)₃Cl₂ ( 1 ), (t-BuP)₃Br₂ ( 2 ), and (t-BuP)₃I₂ ( 3 ), which are formed in the halogenating ring cleavage of tri-tert-butyl-cyclotriphosphane, (t-BuP)₃, by halogens or halogen compounds, favour the erythro, threo configuration by steric reasons. However, the erythro, erythro configurated diastereomer, whose stability depends on the size of the halogen substituents and on the rate of inversion at the phosphorus atoms, is formed initially. The reaction of the erythro, erythro and erythro, threo configurated diastereomers of 1–3 with lithium aluminium hydride leads stereospecifically to the threo, threo and threo, erythro configurated diastereomers of 1,2,3-tri-tert-butyltriphosphane, H₂(t-BuP)₃ ( 4 ), respectively.     

Beiträge zur Chemie des Phosphors. 105. 1,2,3,4-Tetraphenyl-1,4-bis(trimethylsilyl)-tetraphosphan und 1,2,3,4-Tetraphenyltetraphosphan

Contributions to the Chemistry of Phosphorus. 105. 1,2,34-Tetraphenyl-1,4-bis(trimethylsilyl)-tetraphosphane and 1,2,3,4-Tetraphenyltetraphosphane 1,2,3,4-Tetraphenyl-1,4-bis(trimethylsilyl)-tetraphosphane, Me₃Si? (PPh)₄? SiMe₃ ( 1 ), is obtained by reacting K₂(PPh)₄ with trimethylchlorosilane under suitable conditions. Compound 1 disproportionates almost easier than the corresponding triphosphane (Me₃Si)₂(PPH)₃. Of the six possible diastereomers only 1a (erythro, meso, erythro), 1b (erythro, d,l, erythro), 1 d (threo, d,l, threo), and 1 f (erythro, threo, threo) can be detected in solution by ³¹P-NMR spectroscopy. In consequence of rapid inversion at the P atoms a dynamic equilibrium exists between the different isomers. The assignment of the ³¹P-NMR-spectroscopically observed spin systems to the corresponding diastereomers results from the dependence of the ¹J_PP-coupling constants on the dihedral angle between vicinal free electron pairs as well as on the observed frequency distribution. In the alcoholysis of 1 the corresponding hydride H? (PPh)₄? H ( 2 ) is formed as the main product. It could be isolated in spite of its instability. At room temperature 2 disproportionates rapidly forming mainly (PPh)₄ and H₂(PPh)₂ (ratio 1:2) at first; later on also H₂(PPh)₃, H₂PPh, and (PPh)₅ are found. The corresponding rearrangements follow a four-center mechanism involving predominantly P? P bonds.     

Copper-catalyzed denitrogenative N-arylation of sulfoximines and sulfonamides with arylhydrazines

A Cu-mediated ligand-free arylation of NH-sulfoximines and sulfonamides by arylhydrazine hydrochlorides was herein demonstrated. The oxidative transformation provided an easy access towards N-aryl sulfoximines and sulfonamides in high yields (up to 93% yields) with broad functional groups tolerance (up to 36 examples). The protocol was proposed to take place through the free radical pathway based on the results of control reactions and EPR analysis.     

1H- und 13C-NMR-Untersuchungen zur Struktur N-substituierter Tetrazole—Die Strukturen des N-Methoxycarbonyl-, N-Acetyl- und N-(Tri-n-butylstannyl)-tetrazols sowie Substituenteneffekte auf δ13C und 1J(CH)

The ¹H and ¹³C NMR spectra of several isomeric N-substituted tetrazoles have been investigated. ¹³C NMR is shown to be more useful for distinguishing between structural isomers of N-substituted tetrazoles except for those carrying electropositive substituents like SnBu₃. Correlations of δC-5 (inverse) and ¹J(C-5,H) with s?₁ found for 1-substituted tetrazole allowed the identification of the N SnBu₃ derivative as 1-(tri-n-butylstannyl)tetrazole. The phenyl carbon chemical shift difference ΔC′ = δC-3′-δC-2′ is insignificant for structure elucidation and conformational studies of N-substituted 5-phenyltetrazoles; ΔH′ from ¹H NMR spectra seems to be more useful.     

Stereochemically general approach to adjacent bis(tetrahydrofuran) cores of annonaceous acetogenins

A series of six 2,5-disubstituted adjacent bis(tetrahydrofuran) stereoisomers with trans/erythro/cis, trans/threo/trans, or cis/threo/cis relative stereochemistry have been synthesized from known dihydroxycyclooctenes via ring opening/cross metathesis and Pd(0)-mediated asymmetric double cycloetherification. The stereochemistry of four of these isomers has been found in the biologically active annonaceous acetogenin natural products. [reaction: see text].     

The role of trimethylsilyl group in highly stereoselective eposidation of allylic alcohols

The epoxidation of allylic alcohols carrying Me₃Si group on the double bonds with VO(acac)2-tBuOOH or MCPBA provides erythro or threo epoxy alcohols, respectively with high stereoselectivity.     

Do the solvolysis reactions of secondary substrates occur by the S<Subscript>N</Subscript>1 or S<Subscript>N</Subscript>2 mechanism: or something else?

Primary and methyl aliphatic halides and tosylates undergo substitution reactions with nucleophiles in one step by the classic S_N2 mechanism, which is characterized by second-order kinetics and inversion of configuration at the reaction center. Tertiary aliphatic halides and tosylates undergo substitution reactions with nucleophiles in two (or more) steps by the classic S_N1 mechanism, which is characterized by first-order kinetics and incomplete inversion of configuration at the reaction center due to the presence of ion pairs. When the nucleophile is also the solvent, the substitution reaction is called a solvolysis, and both the S_N2 and S_N1 reactions now obey first-order kinetics. Schleyer and Bentley have provided solid, but not conclusive, evidence that secondary substrates undergo solvolysis by a merged mechanism, one that blends characteristics of both the S_N2 and S_N1 mechanisms. The following paper presents the history of their sustained pursuit of a merged mechanism and subsequent rebuttals to this claim. Several issues related to the philosophy and sociology of science are also discussed.     

Adducts of phenoxathiin and thianthrene cation radicals with alkenes and cycloalkenes

Phenoxathiin cation radical perchlorate (PO.+ClO4(-)) added stereospecifically to cyclopentene, cyclohexene, cycloheptene, and 1,5-cyclooctadiene to give 1,2-bis(5-phenoxathiiniumyl)cycloalkane diperchlorates (4-7) in good yield. The diaxial configuration of the PO+ groups was confirmed with X-ray crystallography. Unlike additions of thianthrene cation radical perchlorate (Th.+ClO4(-)) to these cycloalkenes, no evidence for formation of monoadducts was found in the reactions of PO.+ClO4(-). This difference is discussed. Addition of Th.+ClO4(-) to five trans alkenes (2-butene, 2-pentene, 4-methyl-2-pentene, 3-octene, 5-decene) and four cis alkenes (2-pentene, 2-hexene, 2-heptene, 5-decene) gave in each case a mixture of mono- and bisadducts in which the configuration of the alkene was retained. Thus, cis alkenes gave erythro monoadducts and threo bisadducts, whereas trans alkenes gave threo monoadducts and erythro bisadducts. In these additions to alkenes, cis alkenes gave predominantly bisadducts, while trans alkenes (except for trans-2-butene) gave predominantly monoadducts. This difference is explained. 1,2-Bis(5-phenoxathiiniumyl)cycloalkanes (4-7) and 1,2-bis(5-thianthreniumyl)cycloalkanes underwent fast elimination reactions on activated alumina forming, respectively, 1-(5-phenoxathiiniumyl)cycloalkenes (8-11) and 1-(5-thianthreniumyl)cycloalkenes (12-16). Among adducts of Th.+ClO4(-) and alkenes, monoadducts underwent fast ring opening on alumina to give (5-thianthreniumyl)alkenes, while bisadducts underwent fast eliminations of H+ and thianthrene (Th) to give (5-thianthreniumyl)alkenes also. Ring opening of monoadducts was a stereospecific reaction in which the configuration of the original alkene was retained. Thus, erythro monoadducts (from cis alkenes) gave (E)-(5-thianthreniumyl)alkenes and threo monoadducts (from trans alkenes) gave (Z)-(5-thianthreniumyl)alkenes. Among bisadducts, elimination of a proton and Th occurred and was more complex, giving both (E)- and (Z)-(5-thianthreniumyl)alkenes. These results are explained. Configurations of adducts and (5-thianthreniumyl)alkenes were deduced with the aid of X-ray crystallography and (1)H and (13)C NMR spectroscopy. In the NMR spectra of (E)- and (Z)-(5-thianthreniumyl)alkenes, the alkenyl proton of Z isomers always appeared at a lower field (0.8-1.0 ppm) than that of E isomers.     

Synthesis of enantiomerically pure 2-amino alcohols from amino acids mediated by sulfoxides

Enantiomerically pure (R₁,S₂)- and (S₁,S₂)-2-amino alcohols can be easily synthesized by stereodivergent reduction of α′-(N-Boc)amino β-keto sulfoxides (easily synthesized from readily available N-Boc amino ester hydrochlorides) with DIBAH (de 82–92%) and DIBAH/ZnBr₂ (de 80%), followed by hydrogenolysis of the C–S bond of the resulting hydroxy sulfoxides and final hydrolysis of the N-Boc protecting group.     

The use of 15N-NMR spectroscopy for assigning the structures of isomeric N7- and N9-substituted purines

An ¹⁵N-NMR study has shown a considerable difference in electronic structures between the isomeric N⁷ and N⁹ substituted purines. A comparison of ¹⁵N chemical shifts amongst the seven pairs of N⁷ and N⁹ isomers has revealed that (1) the N³ resonances are shielded by 18–20 ppm in an N⁹ isomers; (2) the amino nitrogens at the C-2 or at C-6 positions are always shielded by 3–4 ppm in the N⁷ isomers; (3) the N⁷ chemical shifts in the N⁷ isomers are always more shielded by 6–7 ppm than the N⁹ resonances in the N⁹ isomers. It has a also been found by protonation studies that the N⁹ of the N⁷ isomer is much more basic than the N⁷ of the N⁹ isomer.     

A stereochemical study of optically active thiazolidines

We report a stereochemical study of a series of free N-H and N-methylated 1,3-thiazolidines bearing H or CH₃ at C-(2). These compounds were readily prepared from ephedrine and pseudoephedrines. The stereochemistry of the compounds under study was deduced using ¹H and ¹³C NMR spectroscopy. Two isomers were found for compounds having a methyl group at C-(2) (i.e. C-(2)HCH₃); interconversion of these isomers, presumably via a non-cyclic zwitterionic intermediate, was observed.