Reaction of Bicyclo[3.2.1]octenols with Thionyl Chloride. Preliminary paper

The allylic 1-methyl-3-bromobicyclo[3.2.1]octenyl exo-2 and exo-4 alcohols were treated with thionyl chloride in ether or pentane solution at 0°. In each case, a 50/50 mixture of exo allylic chlorides was obtained. No evidence for a predominant S_N l′ reaction was detected; reported cases of such S_N l′ processes using these conditions should therefore be treated with reserve.     

Synthesis of S-Glycosyl Xanthates by Phase Transfer Catalyzed Substitution of Glycosyl Halides

Abstract

Peracetylated glycosyl- and glycobiosyl bromides and chlorides 1-4 including acetochloroneuraminic acid 5 were stereoselectively transformed into their corresponding S-glycosyl xanthates 6-10 in high yield (91-98%) under phase transfer catalyzed conditions. The reactions occurred at room temperature using tetrabutylammonium hydrogen sulfate as the catalyst. The substitutions gave complete inversion of configuration and thus proceeded by an S_N2 type mechanism. Changing the organic solvent from methylene chloride to ethyl acetate had no detrimental effect on the outcome of the reactions but avoided an undesirable side reaction between the xanthate anion and methylene chloride.     

Oxamic acid derivaties in heterocyclic synthesis: Preparation of 1,2,4-triazolo[1,5-a]pyrazine derivatives

N-Aryl-N-(α-phenylphenacyl)oxamoyl chlorides react with N³-arylsubstituted amidrazones to give functionalized 1,2,4-triazoles which undergo ring-closure by the action of thionyl chloride to give 1,2,4-triazolo[1,5-a]-pyrazinium chlorides in excellent yields.     

Parallelism Between Nucleophilically Solvent-Assisted and Phenyl-Assisted Reactions. Possible Existence of Nucleophilically β-Phenyl-Solvated Ion Pairs

Solvolysis rate constants in M_eOH and t-BuOh are compared for β-methyl and β-phenyl derivatives of two cycloakyl systems. It appears that the β-phenyl derivatives solvolyse at te same rate as the β-methyl ones. The lack of deceleration is attributed to phenyl assistance. It is established by configurational analysis of the reaction products, that those products which necessarily originate from a cationic species are the most abundant ones. It is suggested that these reactions could proceed through ion-pair intermediates, which are nucleophilically solvated by phelyl or by the solvent. A parallel between phenyl assistance and ‘S_N2 (intermediate)’ mechanism, suggested by Bentely & Schleyer, is drawn.     

SN1‐SN2 and SN2‐SN3 mechanistic changes revealed by transition states of the hydrolyses of benzyl chlorides and benzenesulfonyl chlorides

Hydrolysis reactions of benzyl chlorides and benzenesulfonyl chlorides were theoretically investigated with the density functional theory method, where the water molecules are explicitly considered. For the hydrolysis of benzyl chlorides (para‐Z? C₆H₄? CH₂? Cl), the number of water molecules (n) slightly influences the transition‐state (TS) structure. However, the para‐substituent (Z) of the phenyl group significantly changes the reaction process from the stepwise (S_N1) to the concerted (S_N2) pathway when it changes from the typical electron‐donating group (EDG) to the typical electron‐withdrawing one (EWG). The EDG stabilizes the carbocation (MeO? C₆H₄? CH₂⁺), which in turn makes the S_N1 mechanism more favorable and vice versa. For the hydrolysis of benzenesulfonyl chlorides (para‐Z? C₆H₄? SO₂? Cl), both the Z group and n influence the TS structure. For the combination of the large n value (n > 9) and EDG, the S_N2 mechanism was preferred. Conversely, for the combination of the small n value and EWG, the S_N3 one was more favorable. © 2014 Wiley Periodicals, Inc.     

N‐Alkyl Ammonium Resorcinarene Salts as High‐Affinity Tetravalent Chloride Receptors

N‐Alkyl ammonium resorcinarene salts (NARYs, Y=triflate, picrate, nitrate, trifluoroacetates and NARBr) as tetravalent receptors, are shown to have a strong affinity for chlorides. The high affinity for chlorides was confirmed from a multitude of exchange experiments in solution (NMR and UV/Vis), gas phase (mass spectrometry), and solid‐state (X‐ray crystallography). A new tetra‐iodide resorcinarene salt (NARI) was isolated and fully characterized from exchange experiments in the solid‐state. Competition experiments with a known monovalent bis‐urea receptor ( 5 ) with strong affinity for chloride, reveals these receptors to have a much higher affinity for the first two chlorides, a similar affinity as 5 for the third chloride, and lower affinity for the fourth chloride. The receptors affinity toward chloride follows the trend K₁?K₂?K₃≈ 5 >K₄, with K_a=5011 m ^?1 for 5 in 9:1 CDCl₃/[D₆]DMSO.     

Starch Derivatives of High Degree of Functionalization 11: Studies on Alternative Acylation of Starch with Long-chain Fatty Acids Homogeneously in <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dimethyl acetamide/LiCl

Starch materials of different amylose content were allowed to react with saturated and unsaturated fatty acids of varying chain length from C₁₄ to C₁₈ under homogeneous conditions applying the solvent N,N-dimethyl acetamide in combination with LiCl. As reagent the corresponding acid chlorides and, alternatively, carboxylic acids in situ activated with toluene-4-sulfonyl chloride and N,N′-carbonyldiimidazole (CDI) were studied. Using fatty acid chlorides (FACl) and toluene-4-sulfonyl chloride-activated acids an almost complete substitution of the starch occurs. By in situ activation of the fatty acids with CDI, products with a degree of substitution up to 2 were obtained, which, in particular, represents a simple and very mild procedure.     

An Efficient Method for the Synthesis of N-Acylsulfonamides: One-pot Sulfonylation and Acylation of Primary Arylamines under Solvent-Free Conditions

Summary. The preparation of N-acylsulfonamides is described using primary amines, arylsulfonyl chlorides and acyl chlorides. Reaction of primary aryl amines with arylsulfonyl chlorides in the presence of NaHCO₃ produced N-arylsulfonamides, which reacted in situ with benzoyl chloride furnishing the corresponding N-benzoyl-N-arylsulfonamides in 72–96% yields. Accordingly, 4-nitrobenzoyl chloride and 3,5-dinitrobenzoyl chloride were used as acylating agents. All the reactions were carried out under solvent-free conditions at room temperature and the products were isolated after simple work-up in high yields and purity.     

Tetracycline hydrochloride: a synchrotron microcrystal study

The title compound, [(4S,4aS,5aS,6S,12aS)‐2‐amino­hydroxy­methyl­ene‐1,2,3,4,4a,5,5a,6,11,12a‐deca­hydro‐6,10,12,12a‐tetra­­hydroxy‐6‐methyl‐1,3,11‐trioxo­naphthacen‐4‐yl]­di­methyl­amm­onium chloride, C₂₂H₂₅N₂O₈⁺·Cl^?, a well known antibiotic, has been structurally characterized from an individual coarse powder grain by use of high‐intensity synchrotron radiation, in conjunction with an exercise in ab initio powder diffraction structure solution. Free refinement of all H atoms establishes the major tautomeric form of the protonated tetracycline mol­ecule without prejudice. The mol­ecule has extensive intramolecular hydrogen bonding involving most of the potential donors and acceptors, and all intermolecular hydrogen bonding uses the chloride anion as acceptor.     

2,3,5,6-tetramethylmorpholine. VI. Cyclization of N-substituted 3,3′-iminobis-2-butanols

The cyclization of N-substituted 3,3′-iminobis-2-butanols to N-substituted 2,3,5,6-tetramethylmorpholines in sulfuric acid is studied. The ring closure seems to be exclusively a normal S_N2-type substitution with partial inversion of configuration before the cyclization. The steric influence of the N-substituents on the S_N2-reaction and on the inversion is discussed.     

One‐Pot Synthesis of Sulfonamides and Sulfonyl Azides from Thiols using Chloramine‐T

A convenient synthesis of sulfonamides and sulfonyl azides from thiols is described. In situ preparation of sulfonyl chlorides from thiols was accomplished by oxidation with chloramine‐T (=N‐chlorotosylamide=N‐chloro‐4‐methylbenzenesulfonamide), tetrabutylammonium chloride (Bu₄NCl), and H₂O. The sulfonyl chlorides were then further allowed to react with excess amine or NaN₃ in the same pot.     

Rearrangement reactions of aziridinylbenzaldoximes

Reactions of 2,2-dimethylaziridine with benzohydroximoyl chlorides [ArC(Cl)?NOH] give aziridinylbenzaldoximes 1 . It has been found that the aziridine ring in these compounds undergoes ring opening in hydrogen chloride-dioxane solution to give (Z)-N-hydroxy-N′-(2-chloro-2-methylpropyl)benzenecarboximidamides [ArC(NHCH₂CR¹R²Cl)?NOH, 4 ]. Treatment of 1 with hydrochloric acid followed by neutralization with aqueous sodium hydroxide gave 6,6-dimethyl-3-aryl-1,2,4-oxadiazines 2. Reaction of 4 with sodium hydride in dioxane gave 5-isopropyl-3-aryl-4,5-dihydro-1,2,4-oxadiazoles 5. Reaction of the 4,5-dihydro-1,2,4-oxadiazoles 5 with N-chlorosuccinimide gave the heteroaromatic 1,2,4-oxadiazoles 6 . It is suggested that reactions of 4 with sodium hydride in dioxane solution involve the conjugate base of 4 which undergoes a 1,2-hydride shift that is concerted with loss of chloride ion. In aqueous sodium hydroxide solution it is suggested that the conjugate base of 4 undergoes ionization of the chlorine atom followed by nucleophilic attack by the oximate anion.     

Polycondensed heterocycles. III. Synthesis of 5,11-dioxo-1,2,3,1 1a-tetrahydro-5H,11H- and 5-oxo-2,3,11,1 1a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzothiazepine

The syntheses of 5,11-dioxo-1,2,3,11a-tetrahydro-5H11H- and 5-oxo-2,3,11,11a-tetrahydro-1H,5H-pyrrolo-[2,1-c][1,4]benzothiazepine 10 and 11 have been studied. The former was obtained by intramolecular cyclization with CDI of N-(2-mercaptobenzoyl)-L-proline 19 , prepared on one hand by demethylation of N-(2-methylthiobenzoyl)-L-proline t-butyl ester 15 , obtained via the Pummerer rearrangement of the corresponding sulphoxide 17 and successive alkaline hydrolysis, and by deprotection of the mercapto ester 18 with TFA or trimethylsilyl iodide. The ester 15 was achieved by reaction of o-(methylthio)benzoic acid 12 with L-proline t-butyl ester or by treatment of the corresponding acid chloride 13 with L-proline and successive esterification of N-(2-methylthiobenzoyl)-L-proline 16 . On the other hand the proline 19 was also obtained by reduction with sodium dithionite of (S)-bis[2-[[2-(hydroxycarbonyl)-1-pyrrolidinyl]carbonyl]phenyl] disulphide 20 , prepared by condensation of bis(2-chlorocarbonylphenyl) disulphide 14 with L-proline. The reduction of (S)-bis[2-[[2-(chloromethyl)-1-pyrrolidinyl]carbonyl]phenyl] disulphide 28 with sodium borohydride in boiling ethanol afforded directly the benzothiazepinone 11 in 85% yield. The disulphide 28 was synthesized treating the corresponding alcohol 24 or N-(2-mercaptoben-zoyl)-L-prolinol 25 with thionyl chloride. Compound 25 was obtained by demethylation of the corresponding methylthio ether 26 oxidized to sulphoxide 27 via the Pummerer rearrangement. The acid chloride 14 by condensation with (S)-2-(chloromethyl)pyrrolidine hydrochloride gave disulphide 28 as well. The acid chlorides 13 and 14 by reaction with L-prolinol provided respectively alcohols 26 and 24 . Attempts to cyclodehydrate the mercapto alcohol 25 , obtained also by reduction of disulphide 24 , failed.     

A Novel One‐Pot Conversion of Allyl Alcohols into Primary Allyl Halides Mediated by Acetyl Halide

A new and simple method for the synthesis of the primary allyl chlorides and bromides 9 – 16 from the secondary or tertiary allyl alcohols 3 – 8 and acyl halide was developed (Scheme 2, Table 1). Non‐commercially available secondary and tertiary allyl alcohols were synthesized from the related ketones and aldehydes via the addition of vinylmagnesium chloride. Mechanistic studies indicate that the alcohols were first acetylated by the acetyl halide and then protonated prior to substitution by the halide, Cl^? or Br^?, via an S_N2′ reaction, to yield the primary halides (Scheme 5).     

Photoelectron spectra andab initio calculations of the electronic structure of amino-n-sulfenyl chlorides

The electronic structure of some amino-N-sulfenyl chlorides and related compounds is studied by photoelectron spectroscopy and ab initio calculations. Similar values of IP(n _S ) and IP(n _N ) and the total energy minimum indicate that in stable conformations the n _S and n _N orbitals are orthogonal. These conformers are characterized by an effective n_N-σ _S-Cl ^* interaction. The relationship between the intramolecular shift of charge and ionization potential values and the spatial structure of amino-N-sulfenyl chlorides is analyzed. A. E. Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences. Translated fromZhurnal Strukturnoi Khimii, Vol. 35, No. 2, pp. 69–73, March–April, 1994. Translated by L. Smolina     

Two stereoisomeric pentacyclic oxin­dole alkaloids from Uncaria tomentosa: uncarine C and uncarine E

The chloro­form solvate of uncarine C (pteropodine), (1′S,3R,4′aS,5′aS,10′aS)‐1,2,5′,5′a,7′,8′,10′,10′a‐octa­hydro‐1′‐methyl‐2‐oxospiro­[3H‐indole‐3,6′(4′aH)‐[1H]­pyrano­[3,4‐f]indolizine]‐4′‐carboxyl­ic acid methyl ester, C₂₁H₂₄N₂O₄·CHCl₃, has an absolute configuration with the spiro C atom in the R configuration. Its epimer at the spiro C atom, uncarine E (isopteropodine), (1′S,3S,4′aS,5′aS,10′aS)‐1,2,5′,5′a,7′,8′,10′,10′a‐octahydro‐1′‐methyl‐2‐oxospiro[3H‐indole‐3,6′(4′aH)‐[1H]pyrano[3,4‐f]indolizine]‐4′‐carboxylic acid methyl ester, C₂₁H₂₄N₂O₄, has Z′ = 3, with no solvent. Both form intermolecular hydrogen bonds involving only the ox­indole, with N?O distances in the range 2.759 (4)–2.894 (5) Å.     

Synthesis of S‐Aryl Arenethiosulfonates from N,N‐Di(arenesulfonyl)hydrazines: Reduction of Sulfonyl Chlorides with an Organic Reagent

N,N‐Di(arenesulfonyl)‐N′,N′‐dimethyl‐hydrazines, readily prepared from arenesulfonyl chlorides and N,N‐dimethylhydrazine, were heated at 120°C in chlorobenzene to give S‐aryl arenethiosulfonates, ArSSO₂Ar, in good yields.     

Synthesis,characterization and antibacterial activity of indium(III) complexes with adamantane-ring containing Schiff bases

Indium(III) chloride tetrahydrate and Schiff-base ligands derived from adamantaneamine and 3-/4-methoxysalicylaldehyde gave two complexes, C₂₂H₃₂Cl₃InN₂O₃ (1) and C₃₆H₄₄C_l3InN₂O₄ (2), respectively. The complexes were characterized by IR, ¹H NMR, elemental analysis, molar conductance, thermal analysis, and single-crystal X-ray diffraction. Complex 1 crystallizes in the monoclinic system, P2₁/n space group with the asymmetric unit consisting of one indium(III), one N-(3-methoxysalicylidene)-aminoadamantane (L¹), three chlorides and one N,N-dimethylformamide molecule. The indium is six-coordinate with reversed triangular-prism geometry via three oxygens and three chlorides. Complex 2 crystallizes in the triclinic system, P 1 space group; the asymmetric unit consists of one indium(III), two N-(4methoxysalicylidene)-aminoadamantane (L²), and three chlorides. The indium is five-coordinate with distorted trigonal-bipyramidal geometry via two oxygens and three chlorides. Antibacterial activities of the complexes have been investigated against Escherichia coli and Staphylococcus aureus.     

Ion radicals. XIII. Spectroscopic and cryoscopic characterization of ions and ion radicals from phenothiazine and N-methylphenothiazine in sulfuric acid solutions

The formation and interconversion of the N-methylphenothiazine cation radical and the N-methylphenothiazine dication from both N-methylphenothiazine and N-methylphenothiazine S-oxide in sulfuric acid solutions have been demonstrated with e.s.r. and absorption spectroscopy. Cryoscopic measurements have shown that in slightly aqueous sulfuric acid N-methylphenothiazine S-oxide is converted to the N-methylphenothiazine dication and, analogously, phenothiazine 5-oxide is converted to the protonated phenazathionium ion (the phenothiazine dication).     

S-ArylN,N-dialkylamidothiosulfates, a novel class of sulfenic acid derivatives

A method for the synthesis ofS-arylN,N-dialkylamidothiosulfates, a novel class of sulfenic acid derivatives, was proposed. The method is based on the reaction of arenesulfenyl chlorides withN,N-dialkylamidosulfinic acids or with secondary amines in liquid SO₂ in the presence of triethylamine. In the presence of halogen-containing Lewis acids,S-arylN,N-dialkyl-amidothiosulfates add to the C=C bonds to give aryl β-haloalkyl sulfides. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1484–1487, August, 2000.