Reduction of Indolin-2-ones and Desulfurization of Indoline-2-thiones to Indoline and Indole Derivatives

Reduction of indolin-2-ones with lithium aluminium hydride (LAH) or diisobutylaluminum hydride (DIBAL) and desulfurization of indoline-2-thiones with Raney-Ni were investigated. Treatment of indoline-2-ones 1 with LAH or DIBAL yield indoles 4 and/or indolines 3 in moderate-to high yield depending on the substituents at N and C(3) of 1 . Indoline-2-thiones 2 were desulfurized with Raney-Ni to give indoles 4 and/or indolines 3 .     

Novel Synthesis of Mafenide and Other Amino Sulfonamides by Electrochemical Reduction of Cyano Sulfonamides

Both aliphatic and aromatic amino sulfonamides such as mafenide ( 1a ) were synthesized in good yields (80–86%) by direct electrochemical hydrogenation of the corresponding nitriles in an undivided cell containing a Ni cathode, a Pt anode, and Raney Ni as catalyst (Table 1). The reaction can be performed without external supply of pressurized gas by in situ generation of H₂. Slightly elevated temperatures (45°) and low current densities (10 mA/cm²) are favorable conditions for this type of electrochemical nitrile hydrogenation. Our synthetic protocol does not require high‐pressure equipment or chemical hazards, is environmentally very friendly, and more economical than traditional methods. The concentration of adsorbed H^. radicals on the catalyst surface can be easily controlled by adjusting the electric potential, which may lead to improved product selectivity and, at the same time, reduces the risk of explosion and fire.     

Exquisite Synthesis of a Designed PAR‐1 Antagonist

The synthesis of a designed, sterically congested geminal dimethyl‐bearing PAR‐1 antagonist was achieved by a route of ten steps, with the oxidation of an electron‐rich benzaldehyde, the construction of a tertiary alkyl azide, and the selective hydrogenolysis of a 1,5‐fused tetrazole to generate the cyclic amidine with Raney‐Ni being the key steps. The selective hydrogenolysis of 1,5‐fused tetrazole to generate the cyclic amidine with Raney‐Ni was discovered and may be generally used for the synthesis of structurally unusual cyclic amidines. Several unsuccessful attempts to construct the desired geminal dimethyl‐bearing cyclic amidine were also discussed.     

The Course of the Catalytic Hydrogenation/Isomerization Reaction of Steroidal Ring B Olefins in the 13β- and 13α-Series

The course of the catalytic hydrogenation and isomerization (H₂/Raney-Ni/dioxane or H₂/Pd/C/EtOH) of Δ^5.7-, Δ⁷-, Δ⁸-, and Δ⁸⁽¹⁴⁾-steroid olefins was shown to depend strongly on the configuration at C(13). The known hydrogenation/isomerization of reactions of Δ^5.7-dienes in the 13β-series to Δ⁷-(H₂/Raney-Ni/dioxane) and Δ⁸⁽¹⁴⁾-olefins (H₂/Pd/C/EtOH) were also confirmed in the 3β, 19-epoxy-13β- and 3-Oxo-19-acetoxy-13β-steroid series (e.g. 32 → 35 → 37 , Scheme 3). On the other hand, in the corresponding 13α-steroid series the same reactions afforded the Δ⁷-. and the Δ⁸-olefins (mixture of products with H₂/Raney-Ni/dioxane; quantitatively the Δ⁸-compounds with H₂/Pd/C/EtOH; s. e.g. Scheme 3). A similar dependence on the C(13) configuration was observed in the allylic oxidation of these olefins with SeO₂ (Fieser's test, see Table), and in the acid catalyzed opening of the 7α, 8α-epoxides (e.g. 60 → 62 + 63 in the 13β-series, and 56 → 64 + 65 in the 13α-series, Scheme 8).     

Homogeneous and heterogeneous asymmetric reactions. Part 5. Diastereoselective and enantioselective hydrogenation of cyclic β-keto esters on modified Raney-nickel catalysts

The hydrogenations of methyl 2-oxoeyclopentanecarboxylate ( 1 ), ethyl 2-oxocyelohexanecarboxylate ( 3 ), and 2-methylcyclohexanone ( 5 ) on unmodified Raney-Ni catalyst lead predominately to the formation of the cis-hydroxy diastereoisomers of 2 , 4 , and 6 , respectively (Scheme 2). In the asymmetric hydrogenations on catalysts modified with chiral tartaric acid ((R, R )-C₄H₆O₆/Raney-Ni and (R, R)-C₄H₆O₆/NaBr/Raney-Ni), the predominance of the cis-isomer increases significantly. The hydrogenations of β-keto esters 1 and 3 proceed with an enantioselectivity of 10–15% on the modified catalysts, while the similar hydrogenation of 5 yields optically inactive 6 . The (1S,2R)-enantiomers of the cis-isomers of 2 and 4 are formed in larger quantity, whereas the (lR,2R)-enantiomers of the corresponding trans-isomers predominate (Scheme 1). The enantioselective formation of trans- 2 and trans- 4 can be interpreted mainly in terms of the asymmetric hydrogenation of cyclic β-keto esters through the keto form, while that of the corresponding cis-hydroxy esters proceeds through the enol form.     

β-Funktionalisierte Hydrazine aus N-Phthalimidoaziridinen und ihre hydrogenolytische N,N-Spaltung zu Aminen

β-Functionalized Hydrazines from N-Phthalimidoaziridines and their Hydrogenolytic N,N-Cleavage to Amines The three N-phthalimido-aziridines 1–3 were reacted with phenol, thiophenol, aniline, p-toluenesulfonic acid, and H₂O in selected combinations. These nucleophiles opened the 3-membered ring to yield the N-phthalimidoamines 4a–d, 5a–d, 6a–c , and 6e ; all these products (except the carbinol 6e ) carry an aryl-substituted functional group on the C-atom vicinal to the N-substituent. Hydrazinolysis of 4, 5, 6a–c , and 6e afforded the β-functionalized hydrazines 7, 8, 9a–c , and 9e . The reducing medium Raney-Ni/N₂H₄ transformed 4, 5, 6a–c , and 6e to the β-functionalized amines 10, 11, 12a–c , and 12e . By a study with the hydrazide 6a and the hydrazine 9a , it was shown that the N,N-cleavage is a catalytic hydrogenolysis by H₂ generated from N₂H₄ with Raney-Ni and that it does not take place on the hydrazide 6 , but rather on the hydrazine 9 , generated as intermediate from 6 with N₂H₄. Spectroscopic data confirmed that the conversions of 1–3 to 4–6 occurred exclusively with inversion and that the resulting configurations remained fully intact during the transformations of 4, 5 , and 6 (via 7, 8 , and 9 ) to 10, 11 , and 12 , respectively.     

Ring Opening of 1‐Azabicyclo[1.1.0]butanes with Hydrazoic Acid – a Facile Access to N‐Unsubstituted Azetidin‐3‐Amines

Sterically congested 1‐azabicyclo[1.1.0]butanes 1 add hydrazoic acid smoothly at 0–5°, giving 3‐azidoazetidines 2 in good to excellent yields. After hydrogenolysis over Pd/C catalyst, compounds 2 were converted into N‐unsubstituted azetidin‐3‐amines 4 . Attempted reduction of 2a with Raney‐Ni led to a mixture of the expected azetidin‐3‐amine 4a and the ring‐enlarged 2,5‐dihydro‐1H‐imidazole derivative 5 .     

Synthesis of New Bis‐imidazole Derivatives

The reaction of aldimines with α‐(hydroxyimino) ketones of type 10 (1,2‐diketone monooximes) was used to prepare 2‐unsubstituted imidazole 3‐oxides 11 bearing an alkanol chain at N(1) (Scheme 2, Table 1). These products were transformed into the corresponding 2H‐imidazol‐2‐ones 13 and 2H‐imidazole‐2‐thiones 14 by treatment with Ac₂O and 2,2,4,4‐tetramethylcyclobutane‐1,3‐dithione, respectively (Scheme 3). The three‐component reaction of 10 , formaldehyde, and an alkane‐1,ω‐diamine 15 gave the bis[1H‐imidazole 3‐oxides] 16 (Scheme 4, Table 2). With Ac₂O, 2,2,4,4‐tetramethylcyclobutane‐1,3‐dithione or Raney‐Ni, the latter reacted to give the corresponding bis[2H‐imidazol‐2‐ones] 19 and 20 , bis[2H‐imidazol‐2‐thione] 21 , and bis[imidazole] 22 , respectively (Schemes 5 and 6). The structures of 11a and 16b were established by X‐ray crystallography.     

Polymerization of 2‐pentene with Ni(II) α‐diimine complex/M‐MAO catalyst and structure of the polymer

Polymerization of 2‐pentene with [ArN?C(An)C(An)·NAr)NiBr₂ (Ar?2,6‐iPr₂C₆H₃)] ( 1‐Ni) /M‐MAO catalyst was investigated. A reactivity between trans‐2‐pentene and cis‐2‐pentene on the polymerization was quite different, and trans‐2‐pentene polymerized with 1‐Ni /M‐MAO catalyst to give a high molecular weight polymer. On the other hand, the polymerization of cis‐2‐butene with 1‐Ni /M‐MAO catalyst did not give any polymeric products. In the polymerization of mixture of trans‐ and cis‐2‐pentene with 1‐Ni /M‐MAO catalyst, the M_n of the polymer increased with an increase of the polymer yields. However, the relationship between polymer yield and the M_n of the polymer did not give a strict straight line, and the M_w/M_n also increased with increasing polymer yield. This suggests that side reactions were induced during the polymerization. The structures of the polymer obtained from the polymerization of 2‐ pentene with 1‐Ni /M‐MAO catalyst consists of ? CH₂? CH₂? CH(CH₂CH₃)? , ? CH₂? CH₂? CH₂? CH(CH₃)? , ? CH₂? CH(CH₂CH₂CH₃)? , and methylene sequence ? (CH₂)_n? (n ≥ 5) units, which is related to the chain walking mechanism. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2858–2863, 2008     

Thermoreversible Gelation of Poly(vinylidene fluoride) – Camphor System

Poly (vinylidene fluoride) (PVF₂) produces thermoreversible gel in camphor when quenched to 25°C from the melt under sealed condition. The SEM micrograph of dried PVF₂/camphor gel (Wequation/tex2gif-inf-3.gif= 0.25) indicates presence of fibrillar network structure and the gels at different composition shows reversible first order phase transition. The phase diagram of the gel suggest the formation of a polymer- solvent complex. The melting enthalpy gives a stoichiometric composition of the complex at Wequation/tex2gif-inf-5.gif= 0.25. This corresponds to a molar ratio of PVF₂ monomer/camphor ≈ 4/5. Temperature-dependent synchroton experiments further support the conclusions derived from the phase diagram.     

Hydrodeoxygenation of Anisole over Ni/α-Al2O3 Catalyst

Ni-based catalysts supported on di erent supports (α-Al₂O₃,γ-Al₂O₃, SiO2, TiO₂, and ZrO₂) were prepared by impregnation. Effects of supports on catalytic performance were tested using hydrodeoxygenation reaction (HDO) of anisole as model reaction. Ni/α-Al₂O₃ was found to be the highest active catalyst for HDO of anisole. Under the optimal conditions, the anisole conversion is 93.25% and the hydrocarbon yield is 90.47%. Catalyst characteriza-tion using H₂-TPD method demonstrates that Ni/α-Al₂O₃ catalyst possesses more amount of active metal Ni than those of other investigated catalysts, which can enhance the cat-alytic activity for hydrogenation. Furthermore, it is found that the Ni/α-Al₂O₃ catalyst has excellent repeatability, and the carbon deposited on the surface of catalyst is negligible.     

Synthesis and Selected Reactions of Hydrazides Containing an Imidazole Moiety

The preparation of two types of imidazole derivatives bearing a hydrazide group was achieved by treatment of the corresponding esters with NH₂NH₂?H₂O in MeOH at room temperature. In the case of 4‐(ethoxycarbonyl)‐1H‐imidazole 3‐oxides 3 , hydrazides of type 1 were formed with retention of the N‐oxide structure (Scheme 1). Interestingly, due to a strong H‐bonding, no deoxygenation of the N→O function could be achieved even by treatment of 3 with Raney‐Ni. The second type, 2‐[(1H‐imidazol‐2‐yl)sulfanyl]acetohydrazides 2 , was obtained from 1H‐imidazole‐2(3H)‐thiones 4 in two steps via S‐alkylation with methyl bromoacetate, followed by treatment with NH₂NH₂?H₂O (Scheme 2). An imidazole 7 , containing both types of hydrazide groups, was prepared analogously from ethyl 2,3‐dihydro‐2‐thioxo‐1H‐imidazole‐4‐carboxylate 4d (Scheme 4). Both types of hydrazides, 1 and 2 , were transformed successfully to the corresponding acylhydrazones 8 and 9 , respectively (Scheme 5). Furthermore, it has been shown that hydrazides of type 1 are useful starting materials for the synthesis of 1,2,4‐triazole‐3‐thiones 11 and 1,3,4‐thiadiazole‐2‐amines 12 , bearing an imidazole 3‐oxide moiety (Scheme 7).     

Pteridines. Part LXXXV. Chemical synthesis of deoxysepiapterin and 6-acylpteridines by acyl radical substitution reactions

A new synthesis of deoxysepiapterin ( 2 ), one of the two yellow eye pigments of the Drosophila mutant sepia, is described. The synthetic approach makes use of a homolytic nucleophilic acylation of 7-(alkylthio)pteridine derivatives ( 11, 13, 15, 18, 20 ) leading to the corresponding 6-acyl derivatives ( 21–27 ). Desulfurizations have been achieved for the first time in the pteridine series using Raney-Co,Raney-Cu, or Cu? Al alloy in alkaline medium. Besides cleavage of the C(7)? S bond, further reductions of the C?O group at C(6) and the C(7)?N(8) bond are detected as side reactions leading to 6-(1-hydroxyalkyl) ( 34, 35, 42, 43 ) and 6-acyl-7,8-dihydro derivatives ( 2, 36, 37 ), respectively, The newly synthesized compounds have been characterized by elemental analysis, p_K determination, UV and ¹H-NMR spectra.     

Synthesis of Optically Active 1‐(1‐Phenylethyl)‐1H‐imidazoles Derived from 1‐Phenylethylamine

The three‐component reaction of (R)‐ or (S)‐1‐phenylethylamine ( 6 ), formaldehyde, and an α‐(hydroxyimino) ketone 5 , i.e., 3‐(hydroxyimino)butan‐2‐one ( 5a ) or 2‐(hydroxyimino)‐1,2‐diphenylethanone ( 5b ), yields the corresponding enantiomerically pure 1‐(1‐phenylethyl)‐1H‐imidazole 3‐oxide 7 in high yield (Schemes 2 and 3). The reactions are carried out either in MeOH or in AcOH. Smooth transformations of the N‐oxides into optically active 1‐(1‐phenylethyl)‐1H‐imidazoles 10 and 2,3‐dihydro‐1‐(1‐phenylethyl)‐1H‐imidazole‐2‐thiones 11 are achieved by treatment of 7 with Raney‐Ni and 2,2,4,4‐tetramethyl‐3‐thioxocyclobutanone ( 12 ), respectively (Scheme 4).     

Selective hydrogenation of ergosterol and its acetate.

Selective hydrogenation of ergosterol or its acetate in solution in different solvents over Raney nickel to give 5α-ergosta-7,22-dien-3β-ol or its acetate can be controlled by the addition of paraformaldehyde, acetaldehyde, benzaldehyde, 4-dimethylaminobenzaldehyde, and dimethylaniline, the latter 2 giving the best yield. When using pure solvents 5α-ergost-7-en-3β-ol or its acetate can be obtained in almost quantitative yield.     

An economical synthesis of dibenzocyclamnickel(II) and a metal-free macrocycle with tetramethyl substituents

The cationic dibenzocyclamnickel(II) complex, [Ni(Me₄Bzo₂[14]aneN₄)]²⁺, was obtained in good yield by Fe/HCl reduction of the corresponding tetraazaannulene complex [Ni(Me₄taa)], (1) {Me₄Bzo₂[14]aneN₄ = 5,7,12,14-tetramethyldibenzo[b,i]-1,4,8,11-tetraazacyclotetradecane; Me₄taa = 5,7,12,14-tetramethyldibenzo[b,i]-1,4,8,11-tetraazaannulene(2-)}. The orange–red product was isolated as the chloride (2) and perchlorate (3) salts. Analogous reduction with Zn/HCl yielded a diprotonated silky-white product [Ni(Me₄Bzo₂[14]aneN₄-H₂)][ZnCl₄]₂, (4). In the dry state, complex (4) is stable only under an HCl atmosphere and readily dissociates to give a solution of (2) when dissolved in polar solvents. Complexes (2) and (3), upon treatment with an excess of aqueous NaCN, undergo facile demetallation yielding the metal free macrocycle Me₄Bzo₂[14]aneN₄, (5). These compounds were characterized using a combination of i.r., u.v.–vis., ¹H-n.m.r., mass spectroscopy and voltammetry techniques. Unlike the parent tetraazaannulene complex (1), the reduced macrocycle complex, [Ni(Me₄Bzo₂[14]aneN₄)]²⁺ exhibits mild catalytic activity towards electro-reduction of CO₂ in MeCN solution.     

Nickel(0) Complexes with Fluorinated Alkyne Ligands and their Reactivity towards Semihydrogenation and Hydrodefluorination with Water

The current work describes the synthesis and full characterization of zerovalent nickel complexes of the type [(dippe)Ni(η²‐C,C‐F_n‐alkyne)] (dippe=1,2‐bis(di‐isopropylphosphino‐ethane), F_n‐alkyne=fluorinated aromatic alkyne, n=1, 3, 5; 3a , 3b , 3c ) and [{(dippe)Ni}₂(μ²‐C,C‐F_n‐alkyne)] ( 4 ). Reactions with complexes 3a , 3b , 3c , and water as the hydrogen source, yield selective semihydrogenation of the bound alkyne to the corresponding alkene, accompanied by partial hydrodefluorination of the aromatic ring. Different alkynes were tested; on using the alkyne with five fluorine atoms over the aromatic ring, partial defluorination was achieved under the mildest reaction conditions, followed in reactivity by the alkyne with three fluorine atoms. The alkyne with only one fluorine atom was barely defluorinated. The use of triethylsilane as a sacrificial hydride source resulted in an overall increase in reactivity towards defluorination.     

Autothermal Reforming of Methane over Ni Catalysts Supported on CuO-ZrO2-CeO2-Al2O3

Ni catalysts supported on various mixed oxides of Al2O3 with rare earth oxide and transitional metal oxides were synthesized. The studies focused on the measurement of the autothermal reforming of methane to hydrogen over Ni catalysts supported on the mixed oxide ZrxCe30-xAl70Oδ (x=5, 10, 15). The catalytic performance of Ni/Zr10Ce20Al70Oδ was better than that of other catalysts. XRD results showed that the addition of Zr to Ni/Ce30Al70Oδ prevented the formation of NiAl2O4 and facilitated the dispersion of NiO. Effects of CuO addition to Zr10Ce20Al70Oδ were also investigated. The activity of Ni catalyst supported on CuO-ZrO2-CeO2-Al2O3 was somewhat affected and the Ni/Cu5Zr10Ce20Al65Oδ showed the best catalytic performance with the highest CH4 conversion, yield of H2, selectivity for H2 and H2/CO production ratio in operation temperatures ranging from 650 to 750℃.     

Bent and linear trinuclear nickel complexes with ligands derived from N -acylsalicylhydrazide ligands: structural characterization and bioactivity

Two trinuclear Ni(II) complexes Ni₃(L₁)₂(py)₂(DMF)(H₂O) (1) and Ni₃(L₂)₂(py)₂(DMF)₂ (2) with two new trianionic pentadentate ligands N-(3,5-dimethylbenzoyl)-salicylhydrazide (H₃L₁) and N-(phenylacetyl)-5-nitrosalicylhydrazide (H₃L₂) have been synthesized and characterized by X-ray crystallography. Nickel ions in the two complexes have square-planar/octahedral/square-planar coordination. Central metal ion and two terminal metal ions in the two complexes are combined by two bridging deprotonated ligands, forming a trinuclear structural unit with an M–N–N–M–N–N–M core. Studies on the trinuclear Ni(II) complexes show that the β-branched N-acylsalicylhydrazide ligands with sterically flexible Cα methylene groups yield linear trinuclear Ni(II) complexes, while α-branched N-acylsalicylhydrazide ligands tend to form bent trinuclear Ni(II) complexes. Antibacterial screening data in a previous study indicates that bent trinuclear Ni(II) compound 1 is more active than linear compound 2 and less active than a tetranuclear nickel compound.