O‐Benzyl‐N‐tert‐butoxy­carbonyl‐N‐methyl‐l‐tyrosine

The crystal structure of the title compound, alternatively called 3‐[4‐(benzyl­oxy)­phenyl]‐2‐(N‐tert‐butoxy­car­bonyl‐N‐methyl­amino)­propi­onic acid, C₂₂H₂₇NO₅, has been studied in order to ex­amine the role of N‐methyl­ation as a determinant of peptide conformation. The conformation of the tert‐butoxy­carbonyl group is trans–trans. The side chain has a folded conformation and the two phenyl rings are effectively perpendicular to one another. The carboxyl­ate hydroxyl group and the urethane carbonyl group form a strong intermolecular O—H?O hydrogen bond.     

Enantioselective Synthesis of Ethyl 4,5,7,8,9‐Penta‐O‐acetyl‐2,6‐anhydro‐ 3‐deoxy‐D‐erythro‐L‐gluca‐nononate: a 2‐Monodeoxygenated Derivative of `2‐Keto‐3‐deoxy‐D‐glycero‐D‐galacto‐nononic Acid'

A study aimed at developing an enantioselective synthesis of the title compound 23 , a 2‐monodeoxy analogue of the naturally occurring (+)‐2‐keto‐3‐deoxy‐D ‐glycero‐D ‐galacto‐2‐nononic acid (KDN), is reported. From D ‐mannose as starting material, the chiral 1,3‐diene 10 , activated by a silyloxy substituent at C(2), was prepared in six steps (Scheme 1). However, the intermediates were often contaminated with varying amounts of by‐products arising from overoxidation during cleavage with periodic acid. An alternative route starting from the inexpensive and readily available D ‐isoascorbic acid ( 12 ), though a little longer than the first, satisfactorily circumvented the purification problem and led to the desired dienes 17 in good yields (scheme 2). The [Co^II(S,S)‐(+)‐salen]‐catalyzed hetero‐Diels‐Alder reactions of the aforementioned dienes with ethyl glyoxylate proceeded smoothly at room temperature, giving the dihydropyrano adducts 18 in moderate yields (Scheme 3). Dihydroxylation of 18a followed by reduction of the keto function gave the desired 4,5‐trans dihydroxy moiety of the KDN framework (Scheme 4, see 21 ). The spectroscopic data of the penta‐O‐acetylated 2‐deoxy‐KDN ethyl ester 23 were consistent with those reported for the corresponding methyl ester derived from natural KDN.     

5‐Acetyl‐2‐amino‐6‐methyl‐4‐phenyl‐4H‐pyran‐3‐carbonitrile and 2‐amino‐5‐benzoyl‐6‐methyl‐4‐phenyl‐4H‐pyran‐3‐carbonitrile acetonitrile solvate

The syntheses, X‐ray structural investigations and calculations of the conformational preferences of the carbonyl substituent with respect to the pyran ring have been carried out for the two title compounds, viz. C₁₅H₁₄N₂O₂, (II), and C₂₀H₁₆N₂O₂·C₂H₃N, (III), respectively. In both mol­ecules, the heterocyclic ring adopts a flattened boat conformation. In (II), the carbonyl group and a double bond of the heterocyclic ring are syn, but in (III) they are anti. The carbonyl group forms a short contact with a methyl group H atom in (II). The dihedral angles between the pseudo‐axial phenyl substituent and the flat part of the pyran ring are 92.7 (1) and 93.2 (1)° in (II) and (III), respectively. In the crystal structure of (II), inter­molecular N—H⋯N and N—H⋯O hydrogen bonds link the mol­ecules into a sheet along the (103) plane, while in (III), they link the mol­ecules into ribbons along the a axis.     

An efficient synthesis of a class of novel N‐Alkyl‐N‐aryl‐4‐hydroxy‐1‐methyl‐2‐oxo‐1,2‐dihydro‐3‐quinolinecarbothioamides

The novel title compounds have been prepared in high yield by an optimized amide coupling followed by a Dieckmann cyclization. Additionally, this new route is amenable to preparative scale synthesis.     

Synthesis of Novel 3‐Acetyl‐2‐Aryl‐5‐(3‐Aryl‐1‐Phenyl‐Pyrazol‐4‐yl)‐2,3‐Dihydro‐1,3,4‐Oxadiazoles

A series of novel pyrazolyl‐substituted 1,3,4‐oxadiazole derivatives ( 4a‐4o ) were prepared by cyclization of the intermediate N′‐((3‐aryl‐l‐phenyl‐pyrazol‐4‐yl)methylene)arylhydrazide with acetic anhydride. The structures of the new compounds were confirmed by IR, ¹H NMR, MS and elemental analysis. Furthermore, preliminary bioassay of some of the title compounds indicated that they exhibited moderate inhibition against HIV‐1 PR.     

Synthesis of 1‐Amino‐5,6‐diaryl‐3‐cyano‐1H‐pyridin‐2‐ones and 6,7‐Diaryl‐4‐cyano‐3‐hydroxy‐1H‐[1,2]diazepines from Isoflavones

The one‐step cyclocondensation of substituted isoflavones (=3‐phenyl‐4H‐1‐benzopyran‐4‐ones) with cyanoacetohydrazide in the presence of KOH afforded a mixture of 1‐amino‐5,6‐diaryl‐3‐cyano‐1H‐2‐pyridin‐2‐ones and 6,7‐diaryl‐4‐cyano‐3‐hydroxy‐1H‐[1,2]diazepines.     

A New Solution—phase Parallel Synthesis of 2—Alkyamino—3—aryl—5—phenylmethylene—3,5—dihydro—4H—imidazol—4—ones

Thirteen new 2-alkylaminoimidazolones(4) wre rapidly synthesized by a new solution-phase parallel synthetic method,which includes aza-Wittig reaction of iminophosphorane(1) with aromatic isocyanate to give carbodi-imide(2) and subsequent reaction of 2 with various aliphatic primary amine in a parallel fashion.The products were confirmed by ^1H NMR,MS,IR and X-ray crystallographic analysis.The unusual selectivity of the cyclization was probably due to the deometry of the guanidine intermediate.     

rac‐5‐Diphenylacetyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine and rac‐5‐formyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine

rac‐5‐Diphenylacetyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine, C₂₆H₂₇NOS, (I), and rac‐5‐formyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine, C₁₃H₁₇NOS, (II), are both characterized by a planar configuration around the heterocyclic N atom. In contrast with the chair conformation of the parent benzothiazepine, which has no substituents at the heterocyclic N atom, the seven‐membered ring adopts a boat conformation in (I) and a conformation intermediate between boat and twist‐boat in (II). The molecules lack a symmetry plane, indicating distortions from the perfect boat or twist‐boat conformations. The supramolecular architectures are significantly different, depending in (I) on C—H...O interactions and intermolecular S...S contacts, and in (II) on a single aromatic π–π stacking interaction.     

Neue molekulare Indium‐Zinn‐Sauerstoff‐ und Indium‐Zinn‐Natrium‐Sauerstoff‐Chlor‐Cluster

Abstract. The five‐membered heteroelement cluster THF · Cl₂In(O^tBu)₃Sn reacts with the sodium stannate [Na(O^tBu)₃Sn]₂ to produce either the new oxo‐centered alkoxo cluster ClInO[Sn(O^tBu)₂]₃ ( 1 ) (in low yield) or the heteroleptic alkoxo cluster Sn(O^tBu)₃InCl₃Na[Sn(O^tBu)₂]₂ ( 2 ). X‐ray diffraction analyses reveal that in compound 1 the polycyclic entity is made of three tin atoms which together with a central oxygen atom form a trigonal, almost planar triangle, perpendicular to which a further indium atom is connected through the oxygen atom. The metal atoms thus are arranged in a Sn₃In pyramid, the edges of which are all saturated by bridging tert‐butoxy groups. The indium atom has a further chloride ligand. Compound 2 has two trigonal bipyramids as building blocks which are fused together at a six coordinate indium atom. One of the bipyramids is of the type SnO₃In with tert‐butyl groups on the oxygen atoms, while the other has the composition InCl₃Na with chlorine atoms connecting the two metals. The sodium atom in 2 has further contacts to two plus one alkoxide groups which are part of a[Sn(O^tBu)₂]₂ dimer disposing of a Sn₂O₂ central cycle. The hetero element cluster in 2 thus combines three closed entities and its skeleton SnO₃InCl₃NaO₂Sn₂O₂ consists of three different metallic and two different non‐metallic elements.     

Synthesis of some new 1‐acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazole

Some new compounds (E)‐3‐aryl‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐prop‐2‐en‐1‐ones 5a–e were prepared by 1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐ethanone and various aromatic aldehydes. Then one pot reaction was happened by compounds 5a–e with hydrazine hydrate in acetic acid or propionic acid, respectively, to give the title compounds 1acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazoles 6a–i . All structures were established by MS, IR, CHN, ¹H‐NMR and ¹³C‐NMR spectral data. J. Heterocyclic Chem., (2012).     

A simple synthesis of 5‐ethoxycarbonyl‐6‐phenyl‐1,3‐dioxin‐4‐ones and ethyl 3‐benzoyl‐4‐oxo‐2,6‐diphenylpyran‐5‐carboxylate

4‐Ethoxycarbonyl‐5‐phenyl‐2,3‐dihydrofuran‐2,3‐dione 1 reacts with aldehydes via the acylketene intermediate 2 giving the 1,3‐dioxin‐4‐ones 3a‐e and the 1,4‐bis(5‐ethoxycarbonyl‐4‐oxo‐6‐phenyl‐4H‐1,3‐dioxin‐2‐yl)benzene 4 , and a one step reaction between dibenzoylmethane and oxalylchloride gave 3,5‐dibenzoyl‐2,6‐diphenyl‐4‐pyrone 7 . The reaction of 1 with dibenzoylmethane, a dicarbonyl compound, provided ethyl 3‐benzoyl‐4‐oxo‐2,6‐diphenylpyran‐5‐carboxylate derivative 9 . Compound 9 was converted into the corresponding ethyl 3‐benzoyl‐4‐hydroxy‐2,6‐diphenylpyridine‐5‐carboxylate derivative 10 via its reaction with ammonium hydroxyde solution in 1 ‐butanol.     

3‐O‐Acetyl‐4‐deoxy‐4‐iodo‐β‐d‐fructo­furan­osyl 2,3,6‐tri‐O‐acetyl‐4‐chloro‐4‐deoxy‐α‐d‐gluco­pyran­oside

At 160 K, the gluco­pyran­osyl ring of the title compound, C₂₀H₂₈ClIO₁₃, has a near‐ideal ⁴C₁ conformation and the fructo­furan­osyl ring has a twist ⁴T₃ conformation. The two hydroxy groups are involved in intra‐ and intermolecular hydrogen bonds, with the latter interactions linking the mol­ecules into infinite one‐dimensional chains. The absolute configuration of the mol­ecule has been determined.     

Synthesis of pinacol esters of 1‐alkyl‐1H‐pyrazol‐5‐yl‐ and 1‐alkyl‐1H‐pyrazol‐4‐ylboronic acids

Starting from 1H‐pyrazol, a wide number of 1‐alkyl‐1H‐pyrazol‐4‐yl and 1‐alkyl‐1H‐pyrazol‐5‐ylboronic acids and their pinacol esters were synthesized and characterized. The key step in the described methodology is the regioselective lithiation of the pyrazole ring. The synthesized pinacolates are stable under prolonged storage and can be used as convenient reagents in organic synthesis.     

Synthesis of 15‐Cyano‐12‐oxopentadecano‐15‐lactone and 15‐Cyano‐ 12‐oxopentadecano‐15‐lactam

15‐Cyano‐12‐oxopentadecano‐15‐lactone was synthesized in 59% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by reaction with trimethylsilylcyanide, hydrolysis, ring‐expansion, and Nef reaction. A two‐step, one‐pot synthesis of intermediate 2‐hydroxy‐4‐(1‐nitro‐2‐oxycyclododecyl)butanenitrile from 3‐(1‐nitro‐2‐oxocyclododecyl)propanal was developed and the conditions for the Nef reaction were studied. 15‐Cyano‐12‐oxopentadecano‐15‐lactam was synthesized in 40% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by Strecker reaction, ring‐expansion, and Nef reaction. The conditions for the Strecker and Nef reactions were studied. The structures of the target compounds, intermediates, and by‐product were characterized by IR, ¹H‐ and ¹³C‐NMR, and elemental analysis or MS.     

Conformational polymorphs of 22‐cyano‐N‐methyl‐5‐phenylpent‐2‐en‐4‐ynamide

Although the two polymorphic modifications, (I) and (II), of the title compound, C₁₃H₁₀N₂O, crystallize in the same space group (P2₁/c), their asymmetric units have Z′ values of 1 and 2, respectively. These are conformational polymorphs, since the mol­ecules in phases (I) and (II) adopt different rotations of the phenyl ring with respect the central 2‐cyano­carboxy­amino­prop‐2‐enyl fragment. Calculations of crystal packing using Cerius² [Molecular Simulations (1999). 9685 Scranton Road, San Diego, CA 92121, USA] have shown that (I) is more stable than (II), by 1.3 kcal mol^?1 for the crystallographically determined structures and by 1.56 kcal mol^?1 for the optimized structures (1 kcal mol^?1 = 4.184 kJ mol^?1). This difference is mainly attributed to the different strengths of the hydrogen bonding in the two forms.     

Microwave‐induced Stereoselectivity in Synthesis of trans‐4‐Aryl‐3‐methyl‐6‐oxo‐4,5,6,7‐tetrahydro‐2H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitriles

A facile synthesis of trans isomers of 4‐aryl‐3‐methyl‐6‐oxo‐4,5,6,7‐tetrahydro ‐ 2H ‐ pyrazolo[3,4‐b]pyridine‐5‐carbonitriles via three‐component condensation reaction of an aldehyde, 3‐amino‐5‐methylpyrazole and ethyl cyanoacetate in acetonitrile has been developed under microwave irradiation. This one‐pot reaction proceeds without any catalyst in short times and gives the product in high selectivities and high yields.     

5‐Acetyl‐2‐amino‐6‐methyl‐4‐(3‐nitrophenyl)‐4H‐pyran‐3‐carbonitrile and 2‐amino‐5‐ethoxycarbonyl‐6‐methyl‐4‐(3‐nitrophenyl)‐4H‐pyrano‐3‐carbonitrile

The structures of the title compounds, C₁₅H₁₃N₃O₄, (I), and C₁₆H₁₅N₃O₅ [IUPAC name: ethyl 6‐amino‐5‐cyano‐2‐methyl‐4‐(3‐nitro­phenyl)‐4H‐pyrano‐3‐carboxyl­ate], (II), are very similar, with the heterocyclic rings adopting boat conformations. The pseudo‐axial m‐nitro­phenyl substituents are rotated by 84.0 (1) and 98.7 (1)° in (I) and (II), respectively, with respect to the four coplanar atoms of the boat. The dihedral angles between the phenyl rings and nitro groups are 12.1 (2) and 8.4 (2)° in (I) and (II), respectively. The two compounds have similar patterns of intermolecular N—H?O and N—H?N hydrogen bonding, which link mol­ecules into infinite tapes along b .     

From the Lithium‐2‐anilide‐2‐fluoro‐1,3‐diaza‐2‐sila‐cyclopentene‐GaCl3 Adduct to 1,4,6‐Triaza‐5‐gallium‐7‐sila‐cyclo‐3‐heptene ‐ Experimental and Quantum‐chemical Results

The lithium salt (HC–NCMe₃)₂SiFNLiR ( 1 ) R = C₆H₃(2,6‐CHMe₂)₂ reacts with trichlorogallium under displacement of the lithium ion by GaCl₃ to give the adduct [(HC–NCMe₃)₂SiFN]^– [(GaCl₃)R·Li(thf)₄]⁺ ( 1 ). Compound 1 thermally loses LiCl and forms the bicyclic ring intermediates V and VI . Compound  VI adds the aniline H₂NC₆H₃(2,6‐CHMe₂)₂ and the unsaturated, seven‐membered ring compound –NCMe₃–CH₂–CH=NCMe₃GaCl₂–NR–SiFNHR– ( 2 ) is obtained. The addition is accompanied by an enamine‐imine‐tautomerism and proves the Lewis acid character of the silicon atom in an unknown 3‐center‐2‐electron interaction of one nitrogen atom with the silicon and gallium atoms. Quantum chemical calculations of the thermal isomerisation process and crystal structures of 1 and 2 are reported.     

4‐Acetonyl­idene‐1‐ethyl‐2,3,4,5‐tetra­hydro‐1H‐1,5‐benzodiazepin‐2‐one

The title compound, C₁₄H₁₆N₂O₂, contains a diazepine ring, which appears in a boat conformation. An intramolecular hydrogen bond is formed between the NH group of the diazepine ring and a carbonyl O atom of one of the side chains.