Deoxy-nitrosugars 15th communication Synthesis of N-acetylneuraminic acid and N-acetyl-4-epineuraminic Acid

A synthesis of N-acetylneuraminic acid ( 1 ) and of N-acetyl-4-epineuraminic acid ( 2 , R = H) from 2-acetamido-4,6-O-benzylidene-1,2-dideoxy-1-nitro-D -mannopyranose ( 3 ) and 2-acetamido-1,2-dideoxy-4,6-O-isopropylidene-1-nitro-D -mannopyranose ( 4 ), respectively, is described. Michael addition of 3 and 4 to tert-butyl 2-(bromomethyl)prop-2-enoate ( 5 ) and subsequent hydrolytic removal of the NO₂ group gave the 4-nonulosonate tautomers 6 / 7 and 8 / 9 , respectively (Scheme). Stereoselective reduction of 6 / 7 and 8 / 9 with NaBH₄/AcOH in dioxane/H₂O yielded 12/13 (94:6) and 14/15 (92:8), respectively. Reduction of 6 / 7 and 8 / 9 in the absence of AcOH or in EtOH gave 12 / 13 (15:85) and 14 / 15 (15:85), respectively. Ozonolysis of 12 and 13 followed by hydrolysis gave tert-butyl neuraminate 22 and tert-butyl 4-epineuraminate 24 , respectively. Ozonolysis of 14 / 15 , separation of the products 20 and 21 , and hydrolytic removal of the isopropylidene groups gave 22 and 24 , respectively. The tert-butyl ester 22 was saponified to give 1 , which was further characterized as the methyl ester 23 . Saponification of 24 gave the crude 4-epimer of 1 , which was converted into the stable Na salt 2 and also into the methyl ester 25 .     

Intermediates of Asymmetric Oxidation Processes Catalyzed by Vanadium(V) Complexes

The [VO(acac)₂]/Schiff base [R-2-(N-3,5-di-tert-butylsalicylidene)amino-2-phenyl-1-ethanol, S-2-(N-3,5-di-tert-butylsalicylidene)amino-3,3-dimethyl-1-butanol, S-2-(N-3,5-di-tert-butylsalicylidene)amino-3-methyl-1-butanol, or R-2-(N-3,5-di-tert-butylsalicylidene)amino-3-phenyl-1-propanol]/H₂O₂ catalytic systems for the asymmetric oxidation of sulfides and the [VO(acac)₂]/(3bR,4aR)-2-(3,4,4-trimethyl-3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)ethanol/tert-butyl hydroperoxide/TBHP and VO(OAlkyl)₃/[2,2]paracyclophane-4-carboxylic acid N-(1,1-dimethylethyl)-N-hydroxamide/TBHP catalytic systems for the asymmetric epoxidation of allylic alcohols were studied using ¹³C, ⁵¹V, and ¹⁷O NMR spectroscopy. The key intermediates of these systems (peroxo and alkylperoxo complexes of vanadium(V)) were detected, their structures in solution were studied, and the reactivity was evaluated.     

5-Deaza-7-desmethylene analogues of 5,10-methylene-5,6,7,8-tetrahydrofolic acid and related compounds: Synthesis and in vitro biological activity

1-[4-(tert-Butyloxycarbonyl)phenyl]-3-pyrrolidinone and 1-[3-(tert-butyloxycarbonyl)phenyl]-4-piperidinone were condensed with ethyl cyanoacetate or malononitrile to form ylidene derivatives, which were then subjected sequentially to (i) catalytic or chemical reduction, (ii) condensation with guanidine, and (iii) gentle tri-fluoroacetic acid treatment to obtain 3-(2,4-diamino-6(5H)-oxopyrimidin-5-yl)-1-(4-carboxyphenyl)pyrrolidine ( 27 ), 4-(2,4-diamino-6(5H)-oxopyrimidin-5-yl)-1-(carboxyphenyl)piperidine ( 35 ), and 3-(2,4,6-triaminopyrimidin-5-yl)-1-(carboxyphenyl)pyrrolidine ( 40 ). Condensation of 27, 35 , and 40 with diethyl or di-tert-butyl L-glutamate followed by removal of the ester groups yielded N-[4-[3-(2,4-diamino-6(5H)-oxopyrimidin-5-yl)pyr-rolidino]benzoyl]-L-glutamic acid ( 13 ), N-[4-[4-(2,4-diamino-6-(5H)-oxopyrimidin-5-yl)piperidino]benzoyl]-L-glutamic acid ( 14 ), and N-[4-[3-(2,4,6-triaminopyrimidin-5-yl)pyrrolidino]benzoyl]-L-glutamic acid ( 15 ). Compounds 13 and 14 may be viewed as 5-deaza-7-desmethylene analogues of 5,10-methylene-5,6,7,8-tetrahydrofolic and 5,10-ethylene-5,6,7,8-tetrahydrofolic acid, respectively. Compounds 13 and 15 were good substrates for mouse liver folylpolyglutamate synthetase, with K_m values of 20 and 18 μM and a relative first-order rate constant V_max/K_m of 2.2 (aminopterin = 1.0). In contrast, 14 was a very poor substrate, with a K_m of 490 μM and a relative V_max/K_m of 0.052. As expected from its structure, 15 was a dihydrofolate reductase inhibitor. However its potency was unexceptional (IC₅₀ = 1.2 μM). Compounds 13 and 14 were inactive at concentrations of up to 100 μM, and likewise showed no activity against thymidylate synthase or glycinamide ribotide formyltransferase, two other key enzymes of folate-mediated one-carbon metabolism. Compound 15 was moderately active as an inhibitor of the growth of cultured tumor cells (SCC25 human squamous cell carcinoma), with an IC₅₀ of 0.37 μM (72 hour exposure). By comparison the IC₅₀ of aminopterin was 0.0069 μM. Thus, even though 15 is a good folylpolyglutamate synthetase substrate, the deep-seated skeletal changes embodied in this structure are unfavorable for DHFR binding and may also be unfavorable for transport into cells.     

A Novel Synthesis of tert- Alkyl Sulfides

tert- Alkyl sulfides are conveniently prepared from α-(1H-benzotriazol-1-yl)alkyl sulfides by displacement of the 1H-benzotriazol-1-yl group with Grignard reagents. The 1-[α-(alkylthio)alkyl]- and 1-[α-(arylthio)alkyl]-1H-benzotriazole intermediates are easily available by several routes: (i) displacement of the halogen from appropriate halides by sodium salts of thiols, (ii) condensation of 1H-benzotriazole and thiols with carbonyl compounds, or (iii) lithiation of N-substituted 1H-benzotriazoles and subsequent treatment with electrophiles.     

Covalent‐assisted supramolecular synthesis: the effect of hydrogen bonding in cocrystals of 4‐tert‐butylbenzoic acid with isoniazid and its derivatized forms

A series of cocrystals of isoniazid and four of its derivatives have been produced with the cocrystal former 4‐tert‐butylbenzoic acid via a one‐pot covalent and supramolecular synthesis, namely 4‐tert‐butylbenzoic acid–isoniazid, C₆H₇N₃O·C₁₁H₁₄O₂, 4‐tert‐butylbenzoic acid–N′‐(propan‐2‐ylidene)isonicotinohydrazide, C₉H₁₁N₃O·C₁₁H₁₄O₂, 4‐tert‐butylbenzoic acid–N′‐(butan‐2‐ylidene)isonicotinohydrazide, C₁₀H₁₃N₃O·C₁₁H₁₄O₂, 4‐tert‐butylbenzoic acid–N′‐(diphenylmethylidene)isonicotinohydrazide, C₁₉H₁₅N₃O·C₁₁H₁₄O₂, and 4‐tert‐butylbenzoic acid–N′‐(4‐hydroxy‐4‐methylpentan‐2‐ylidene)isonicotinohydrazide, C₁₂H₁₇N₃O₂·C₁₁H₁₄O₂. The co‐former falls under the classification of a `generally regarded as safe' compound. The four derivatizing ketones used are propan‐2‐one, butan‐2‐one, benzophenone and 3‐hydroxy‐3‐methylbutan‐2‐one. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and all of its derivatives. The remaining hydrogen‐bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems.     

Four N7‐alkoxybenzyl‐substituted 4,5,6,7‐tetrahydro‐1H‐pyrazolo[3,4‐b]pyridine‐5‐spiro‐1′‐cyclohexane‐2′,6′‐diones: hydrogen‐bonded supramolecular structures in zero,one, two or three dimensions

3‐tert‐Butyl‐7‐(4‐methoxybenzyl)‐4′,4′‐dimethyl‐1‐phenyl‐4,5,6,7‐tetrahydro‐1H‐pyrazolo[3,4‐b]pyridine‐5‐spiro‐1′‐cyclohexane‐2′,6′‐dione, C₃₁H₃₇N₃O₃, (I), 3‐tert‐butyl‐7‐(2,3‐dimethoxybenzyl)‐4′,4′‐dimethyl‐1‐phenyl‐4,5,6,7‐tetrahydro‐1H‐pyrazolo[3,4‐b]pyridine‐5‐spiro‐1′‐cyclohexane‐2′,6′‐dione, C₃₂H₃₉N₃O₄, (II), 3‐tert‐butyl‐4′,4′‐dimethyl‐7‐(3,4‐methylenedioxybenzyl)‐1‐phenyl‐4,5,6,7‐tetrahydro‐1H‐pyrazolo[3,4‐b]pyridine‐5‐spiro‐1′‐cyclohexane‐2′,6′‐dione, C₃₁H₃₅N₃O₄, (III), and 3‐tert‐butyl‐4′,4′‐dimethyl‐1‐phenyl‐7‐(3,4,5‐trimethoxybenzyl)‐4,5,6,7‐tetrahydro‐1H‐pyrazolo[3,4‐b]pyridine‐5‐spiro‐1′‐cyclohexane‐2′,6′‐dione ethanol 0.67‐solvate, C₃₃H₄₁N₃O₅·0.67C₂H₆O, (IV), all contain reduced pyridine rings having half‐chair conformations. The molecules of (I) and (II) are linked into centrosymmetric dimers and simple chains, respectively, by C—H...O hydrogen bonds, augmented only in (I) by a C—H...π hydrogen bond. The molecules of (III) are linked by a combination of C—H...O and C—H...π hydrogen bonds into a chain of edge‐fused centrosymmetric rings, further linked by weak hydrogen bonds into supramolecular arrays in two or three dimensions. The heterocyclic molecules in (IV) are linked by two independent C—H...O hydrogen bonds into sheets, from which the partial‐occupancy ethanol molecules are pendent. The significance of this study lies in its finding of a very wide range of supramolecular aggregation modes dependent on rather modest changes in the peripheral substituents remote from the main hydrogen‐bond acceptor sites.     

Seven 5‐benzylamino‐3‐tert‐butyl‐1‐phenyl‐1H‐pyrazoles: unexpected isomorphisms,and hydrogen‐bonded supramolecular structures in zero,one and two dimensions

5‐Benzylamino‐3‐tert‐butyl‐1‐phenyl‐1H‐pyrazole, C₂₀H₂₃N₃, (I), and its 5‐[4‐(trifluoromethyl)benzyl]‐, C₂₁H₂₂F₃N₃, (III), and 5‐(4‐bromobenzyl)‐, C₂₀H₂₂BrN₃, (V), analogues, are isomorphous in the space group C2/c, but not strictly isostructural; molecules of (I) form hydrogen‐bonded chains, while those of (III) and (V) form hydrogen‐bonded sheets, albeit with slightly different architectures. Molecules of 3‐tert‐butyl‐5‐(4‐methylbenzylamino)‐1‐phenyl‐1H‐pyrazole, C₂₁H₂₅N₃, (II), are linked into hydrogen‐bonded dimers by a combination of N—H...π(arene) and C—H...π(arene) hydrogen bonds, while those of 3‐tert‐butyl‐5‐(4‐chlorobenzylamino)‐1‐phenyl‐1H‐pyrazole, C₂₀H₂₂ClN₃, (IV), form hydrogen‐bonded chains of rings which are themselves linked into sheets by an aromatic π–π stacking interaction. Simple hydrogen‐bonded chains built from a single N—H...O hydrogen bond are formed in 3‐tert‐butyl‐5‐(4‐nitrobenzylamino)‐1‐phenyl‐1H‐pyrazole, C₂₀H₂₂N₄O₂, (VI), while in 3‐tert‐butyl‐5‐(3,4,5‐trimethoxybenzylamino)‐1‐phenyl‐1H‐pyrazole, C₂₃H₂₉N₃O₃, (VII), which crystallizes with Z′ = 2 in the space group P, pairs of molecules are linked into two independent centrosymmetric dimers, one generated by a three‐centre N—H...(O)₂ hydrogen bond and the other by a two‐centre N—H...O hydrogen bond.     

Reactions of Single-electron Oxidation and Reduction of Sulfides of the Azulene Series

Single-electron oxidation in acetonitrile and reduction in DMF of sulfides of 3-RS-1,4-dimethyl-7- ethylazulenes (R = Me, Et, Ph, p-MeC₆H₄, p-MeOC₆H₄, N-1-phenyltetrazolyl) leads to stable radical cations and radical anions, respectively. The found reduction potentials of sulfides of the azulene series are close to those of natural and synthetic bioantioxidants. In the radical cations the unpaired electron is essentially delocalized over the cyclopentadienyl fragment of the molecule, and the sulfide group in large measure defines the distribution of spin density. In the radical anion spin density is delocalized in the tropylium cycle, and the influence of the sulfide group is insignificant. Electrochemical oxidation of unsubstituted 1,4-dimethyl-7-ethylazulene results in the formation of a dimeric radical cation.     

Two isomorphous ZnII/CoII complexes with tri‐tert‐butoxysilanethiol and histamine,and (4‐hydroxymethyl‐1H‐imidazole‐κN)bis(tri‐tert‐butoxysilanethiolato‐κ2O,S)zinc(II)

The complexes [2‐(1H‐imidazol‐4‐yl‐κN³)ethylamine‐κN]bis(tri‐tert‐butoxysilanethiolato‐κS)cobalt(II), [Co(C₁₂H₂₇O₃SSi)₂(C₅H₉N₃)], and [2‐(1H‐imidazol‐4‐yl‐κN³)ethylamine‐κN]bis(tri‐tert‐butoxysilanethiolato‐κS)zinc(II), [Zn(C₁₂H₂₇O₃SSi)₂(C₅H₉N₃)], are isomorphous. The central Zn^II/Co^II ions are surrounded by two S atoms from the tri‐tert‐butoxysilanethiolate ligand and by two N atoms from the chelating histamine ligand in a distorted tetrahedral geometry, with two intramolecular N—H...O hydrogen‐bonding interactions between the histamine NH₂ groups and tert‐butoxy O atoms. Molecules of the complexes are joined into dimers via two intermolecular bifurcated N—H...(S,O) hydrogen bonds. The Zn^II atom in [(1H‐imidazol‐4‐yl‐κN³)methanol]bis(tri‐tert‐butoxysilanethiolato‐κ²O,S)zinc(II), [Zn(C₁₂H₂₇O₃SSi)₂(C₄H₆N₂O)], is five‐coordinated by two O and two S atoms from the O,S‐chelating silanethiolate ligand and by one N atom from (1H‐imidazol‐4‐yl)methanol; the hydroxy group forms an intramolecular hydrogen bond with sulfur. Molecules of this complex pack as zigzag chains linked by N—H...O hydrogen bonds. These structures provide reference details for cysteine‐ and histidine‐ligated metal centers in proteins.     

Isolation and structure of an 18‐membered macrocycle containing two diselenide linkages and its precursor

The structures of the 18‐membered diselenide‐linked macrocycle 10,27‐di‐tert‐butyl 11,28‐dioxo‐2,3,19,20‐tetraselena‐10,12,27,29‐tetraazapentacyclo[28.4.0.0^4,9.0^13,18.0^21,26]tetratriaconta‐1(30),4(9),5,7,13,15,17,21,23,25,31,33‐dodecaene‐10,27‐dicarboxylate, C₃₆H₃₄N₄O₆Se₄, and its precursor di‐tert‐butyl 2,2′‐[diselane‐1,2‐diylbis(2,1‐phenylene)]dicarbamate, C₂₂H₂₈N₂O₄Se₂, are reported. The precusor to the macrocycle contains two tert‐butyl phenylcarbamate arms connected to a diselenide group, with Se—C and Se—Se bond lengths of 1.914 (4) and 2.3408 (6) Å, respectively. The macrocycle resides on a crystallographic center of inversion in space group P with one molecule in the unit cell (Z′ = ). It contains an 18‐membered macrocyclic ring with two diselenide linkages. In this macrocycle, there are two free and two protected amino groups.     

Radical Arylation Reactions of 4, 6, 8-Trimethylazulene

The synthesis of 1- and 2-aryl-substituted (aryl = Ph, 4-NO₂? C₆H₄, and 4-MeO? C₆H₄) 4, 6, 8-trimethylazulenes ( 4 and 3 , respectively) in moderate yields by direct arylation of 4, 6, 8-trimethylazulene ( 8 ) with the corresponding arylhydrazines 13 in the presence of Cu^IIions in pyridine (see Scheme 4) as well as with 4-MeO? C₆H₄Pb(OAc)₃ ( 16 ) in CF₃COOH (see Scheme 5) is described. With 13 , also small amounts of 1, 2- and 1, 3-diarylated azulenes (see 14 and 15 , respectively, in Scheme 4) are formed. The 4-methoxyphenylation of 8 with 16 yielded also the 1, 1′-biazulene 17 in minor amounts (see Scheme 5). 4, 6, 8-Trimethyl-2-phenylazulene ( 3a ) was also obtained as the sole product in moderate yields by the reaction of sodium phenylclopentadienide ( 1a ) with 2, 4, 6-trimethylpyrylium tetrafluoroborate ( 2 ) in THF (Scheme 1). The attempted phenylation of 8 as well as of azulene ( 9 ) itself with N-nitroso-N-phenylacetamide ( 10 ) led only to the formation of the corresponding 1-(phenylazo)-substituted azulenes 12 and 11 , respectively (Scheme 3).     

Eight 7‐benzyl‐3‐tert‐butyl‐1‐phenylpyrazolo[3,4‐d]oxazines,encompassing structures containing no intermolecular hydrogen bonds,and hydrogen‐bonded structures in one,two or three dimensions

7‐Benzyl‐3‐tert‐butyl‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₂H₂₅N₃O, (I), and 3‐tert‐butyl‐7‐(4‐methylbenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₇N₃O, (II), are isomorphous in the space group P2₁, and molecules are linked into chains by C—H...O hydrogen bonds. In each of 3‐tert‐butyl‐7‐(4‐methoxybenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₇N₃O₂, (III), which has cell dimensions rather similar to those of (I) and (II), also in P2₁, and 3‐tert‐butyl‐1‐phenyl‐7‐[4‐(trifluoromethyl)benzyl]‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₄F₃N₃O, (IV), there are no direction‐specific interactions between the molecules. In 3‐tert‐butyl‐7‐(4‐nitrobenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₂H₂₄N₄O₃, (V), a combination of C—H...O and C—H...N hydrogen bonds links the molecules into complex sheets. There are no direction‐specific interactions between the molecules of 3‐tert‐butyl‐7‐(2,3‐dimethoxybenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₄H₂₉N₃O₃, (VI), but a three‐dimensional framework is formed in 3‐tert‐butyl‐7‐(3,4‐methylenedioxybenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₅N₃O₃, (VII), by a combination of C—H...O, C—H...N and C—H...π(arene) hydrogen bonds, while a combination of C—H...O and C—H...π(arene) hydrogen bonds links the molecules of 3‐tert‐butyl‐1‐phenyl‐7‐(3,4,5‐trimethoxybenzyl)‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₅H₃₁N₃O₄, (VIII), into complex sheets. In each compound, the oxazine ring adopts a half‐chair conformation, while the orientations of the pendent phenyl and tert‐butyl substituents relative to the pyrazolo[3,4‐d]oxazine unit are all very similar.     

1,3-Dipolar cycloadditions of diazoalkanes to pyridazine derivatives. Thermal 1,5-sigmatropic rearrangement of methyl groups in 3,3-dimethyl-3H-pyrazolo[3,4-d]pyridazine derivatives

Thermal 1,5-sigmatropic rearrangements of one of the methyl group attached at position 3 of 3,3-dimethyl-3H-pyrazolo[3,4-d]pyridazin-4(5H)-ones 1–3 taking place either in a clock-wise or anti-clockwise direction gave N₂-methylated products 4–6 and C_3a-methylated products 7– 9 . The -7(6)-one derivative 10 and -4,7(5H,6H)-dione derivative 12 gave only N₂-methylated products 11 and 13 respectively, and 1,2-dihydro derivative 14 produced after elimination of methane, 15 .     

Synthesis and chiral recognition properties of poly(N‐propargylamide) gels derived from ornithine and lysine

Copolymerization of ornithine‐ and lysine‐derived N‐propargylamides, N‐α‐tert‐butoxycarbonyl‐N‐δ‐fluorenylmethoxycarbonyl‐L ‐ornithine N′‐propargylamide ( 1 ), N‐α‐tert‐butoxycarbonyl‐N‐ε‐fluorenylmethoxycarbonyl‐L ‐lysine N′‐propargylamide ( 2 ), N‐α‐fluorenylmethoxycarbonyl‐N‐δ‐tert‐butoxycarbonyl‐L ‐ornithine N′‐propargylamide ( 3 ), and N‐α‐fluorenylmethoxycarbonyl‐N‐ε‐tert‐butoxycarbonyl‐L ‐lysine N′‐propargylamide (4) with dipropargyl adipate was carried out using (nbd)Rh⁺[η⁶‐C₆H₅B^?(C₆H₅)₃] as a catalyst in THF to obtain polymer gels in 80–93% yields. The gels adsorbed N‐benzyloxycarbonyl L ‐alanine, N‐benzyloxycarbonyl L ‐alanine methyl ester, and (S)‐(+)‐1‐phenyl‐1,2‐ethanediol preferably than the corresponding optical isomers. The order of chiral discrimination was poly( 1 ) > poly( 4 ) > poly( 2 ), poly( 3 ) gels. The fluorenylmethoxycarbonyl groups of the gels could be partly removed by piperidine treatment, leading to increase of adsorptivity but decrease of chiral recognition ability. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4175–4182, 2008     

Partial Degradation of a CF3 Group by Silylene Attack [1]

The reactions of the 4,5-bis(trifluoromethyl)-1,3,2-diazasilole derivative 1 with the sterically encumbered silylenes R₂Si, R = tBu, 2,4,6-Me₃C₆H₂, proceed by partial degradation of one of the CF₃ groups to furnish the N-di-tert-butylfluorosilyl ( 3 a ) or N-fluorodimesitylsilyl ( 3 b ) substituted 4-difluoromethylene-5-trifluoromethyl-1,3-diaza-2-silacyclopent-5-enes. The structure of 3 a was determined by X-ray crystallography.     

Hydrogen‐bonding patterns in three substituted N‐benzyl‐N‐(3‐tert‐butyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)acetamides

The molecules of N‐(3‐tert‐butyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)‐2‐chloro‐N‐(4‐methoxybenzyl)acetamide, C₂₃H₂₆ClN₃O₂, are linked into a chain of edge‐fused centrosymmetric rings by a combination of one C—H...O hydrogen bond and one C—H...π(arene) hydrogen bond. In N‐(3‐tert‐butyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)‐2‐chloro‐N‐(4‐chlorobenzyl)acetamide, C₂₂H₂₃Cl₂N₃O, a combination of one C—H...O hydrogen bond and two C—H...π(arene) hydrogen bonds, which utilize different aryl rings as the acceptors, link the molecules into sheets. The molecules of S‐[N‐(3‐tert‐butyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)‐N‐(4‐methylbenzyl)carbamoyl]methyl O‐ethyl carbonodithioate, C₂₆H₃₁N₃O₂S₂, are also linked into sheets, now by a combination of two C—H...O hydrogen bonds, both of which utilize the amide O atom as the acceptor, and two C—H...π(arene) hydrogen bonds, which utilize different aryl groups as the acceptors.     

Four oxoindole‐linked α‐alkoxy‐β‐amino acid derivatives

Four structures of oxoindolyl α‐hydroxy‐β‐amino acid derivatives, namely, methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐methoxy‐2‐phenylacetate, C₂₄H₂₈N₂O₆, (I), methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐ethoxy‐2‐phenylacetate, C₂₅H₃₀N₂O₆, (II), methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐[(4‐methoxybenzyl)oxy]‐2‐phenylacetate, C₃₁H₃₄N₂O₇, (III), and methyl 2‐[(anthracen‐9‐yl)methoxy]‐2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐phenylacetate, C₃₈H₃₆N₂O₆, (IV), have been determined. The diastereoselectivity of the chemical reaction involving α‐diazoesters and isatin imines in the presence of benzyl alcohol is confirmed through the relative configuration of the two stereogenic centres. In esters (I) and (III), the amide group adopts an anti conformation, whereas the conformation is syn in esters (II) and (IV). Nevertheless, the amide group forms intramolecular N—H...O hydrogen bonds with the ester and ether O atoms in all four structures. The ether‐linked substituents are in the extended conformation in all four structures. Ester (II) is dominated by intermolecular N—H...O hydrogen‐bond interactions. In contrast, the remaining three structures are sustained by C—H...O hydrogen‐bond interactions.     

Amine exchange reactions of 3-<Emphasis Type="Italic">tert</Emphasis>-butyl-6-(methylsulfanyl)-1,2,3,4-tetrahydro-1,3,5-triazine hydroiodide with amino acids

3-tert-Butyl-6-(methylsulfanyl)-1,2,3,4-tetrahydro-1,3,5-triazine hydroiodide enters into the amine exchange reaction with glycine and β-alanine in aqueous solution. The final exchange products are [4-(methylsulfanyl)-5,6-dihydro-1,3,5-triazin-3-ium-1(2H)-yl] acetate and 3-[4-(methylsulfanyl)-5, 6-dihydro-1,3,5-triazin-3-ium-1(2H)-yl] propanoate, respectively, crystallizing together with t-butylamine hydroiodide from aqueous or aqueous alcoholic solutions as ion associates, which also can be detected in solution in DMSO-d ₆. [4-(Methylsulfanyl)-5,6-dihydro-1,3,5-triazin-3-ium-1(2H)-yl] acetate can be extracted directly from the reaction mixture after carrying out the amine exchange in aqueous isopropanol or 95% ethanol, as well as by “recrystallization“ of its associate with tert-butylamine hydroiodide from aqueous isopropanol.     

3-Hydrazino-1,2,4-triazin-5(2H)-ones in Reactions with Compounds Containing Carbonyl and Active Methylene Groups

Boiling of ethyl cyanoacetate with 6-tert-butyl-3-hydrazino-1'2'4-triazin-5(2H)-one in alkalinemedium yielded 6-tert-butyl-3-(5-hydroxy-3-oxo-2'3-dihydro-1H-pyrazol-1-yl)-1'2'4-triazin-5(2H)-one.Acylation of 6-tert-butyl-3-hydrazino-1'2'4-triazin-5(2H)-one with benzoyl chloride furnished 3-benzoyl-hydrazido-1'2'4-triazine that cyclized when treated with POCl₃ providing a derivative of[1'2'4]triazolo[4'3-b][1'2'4]triazine. Boiling of 6-tert-butyl-3-hydrazino-1'2'4-triazin-5(2H)-one in glacialacetic acid gave rise to diacetylated derivative whereas the boiling with acetic anhydride in an inert solventafforded monoacetylated product.