Sodium Hydrogen Sulfate as Effective and Reusable Heterogeneous Catalyst for the One-pot Preparation of 14H-[(Un)substituted phenyl]-dibenzo[a,j]xanthene Leuco-dye Derivatives

NaHSO₄•H₂O has been used as an efficient catalyst for the one-pot preparation of 14H-[(un)substituted phenyl]-dibenzo[a,j]xanthene leuco-dye derivatives by condensation of β-naphthol with substituted benzaldehydes under microwave and thermal conditions. This method has the advantages of high yields, a green reaction, an efficient and cost-effective method, simple procedures, short reaction time, and easy workup.     

Diversity in Gold‐Catalyzed Formal Cycloadditions of Ynamides with Azidoalkenes or 2H‐Azirines: [3+2] versus [4+3] Cycloadditions

Gold‐catalyzed cycloadditions of ynamides with azidoalkenes or 2H‐azirines give [3+2] or [4+3] formal cycloadducts of three classes. Cycloadditions of ynamides with 2H‐azirine species afford pyrrole products with two regioselectivities when the C_β‐substituted 2H‐azirine is replaced from an alkyl (or hydrogen) with an ester group. For ynamides substituted with an electron‐rich phenyl group, their reactions with azidoalkenes proceed through novel [4+3] cycloadditions to deliver 1H‐benzo[d]azepine products instead.     

Palladium‐Catalyzed Cyclization Reaction of o‐Haloanilines,CO2 and Isocyanides: Access to Quinazoline‐2,4(1H,3H)‐diones

Quinazoline‐2,4(1H,3H)‐diones are core structural subunits frequently found in many biologically important compounds. The reaction of 2‐​aminobenzonitrile and CO₂, which was frequently studied, only provided N3‐unsubstituted quinazoline‐2,4(1H,3H)‐dione compounds. Herein we report palladium‐catalyzed cyclization reactions of o‐haloanilines, CO₂ and isocyanides to prepare N3‐substituted quinazoline‐2,4(1H,3H)‐diones. Electron‐rich o‐bromoanilines participated in the cyclization reaction using Cs₂CO₃ at high temperature, and electron‐deficient o‐bromoaniline or o‐iodoaniline substrates conducted the reaction using CsF as base to deliver corresponding quinazoline‐2,4(1H,3H)‐dione products in good yields.     

Highly Efficient [3 + 2] Cycloaddition: Click Synthesis of Novel 1H‐indol‐3‐yl‐benzo[d]imidazole Bis‐triazoles

A series of novel 1‐((1H‐1,2,3‐triazol‐4‐yl)methyl)‐2‐(1‐((1H‐1,2,3‐triazol‐4‐yl)methyl)‐5‐substituted‐1H‐indol‐3‐yl)‐6‐substituted‐1H‐benzo[d]imidazoles 5a – i have been prepared using click chemistry as an ideal strategy where [3 + 2] cycloaddition of azides with terminal alkynes has been developed as the target compounds. In route‐II, 5‐substituted‐1H‐indole‐3‐carbaldehydes 1a – c react with 5‐substituted orthophenylenediamine 8 to give desired products, that is, 6‐substituted‐2‐(5‐substituted‐1H‐indol‐3‐yl)‐1H‐benzo[d]imidazole 6a – i . Here, 6a – i react with 2 equiv of propargylbromide 7 to give novel 6‐substituted 2‐(5‐substituted‐1‐(prop‐2‐yn‐1‐yl)‐1H‐indol‐3‐yl)‐1‐(prop‐2‐yn‐1‐yl)‐1H‐benzo[d]imidazole 4a – i . 4a – i were reacted with 2 equiv of NaN₃ in t‐butanol/water (1:2) and add catalytic amount of CuSO₄.5H₂O. Stir the reaction mixture at room temperature to get the target products 5a – i . Here, obtained products contain four rings, that is, one indole, two triazoles, and one benzimidazole. The main advantages of this method are short reaction times, easy workup, higher yields (88–92%), and no by‐products formation.     

The synthesis of n‐substituted isothiazol‐3(2h)‐ones from nsubstituted 3‐benzoylpropionamides

N‐Substituted isothiazol‐3(2H)‐ones can be easily prepared from N‐substituted 3‐benzoylpropi‐onamides in two experimentally simple steps, in satisfactory overall yields. Reaction of the amides with excess thionyl chloride results in the formation of N‐substituted 5‐benzoylisothiazol‐3(2H)‐ones, which are readily debenzoylated with alkali to the corresponding N‐substituted isothiazol‐3(2H)‐ones. This method has now been successfully applied to the synthesis of isothiazolones N‐substituted with a bulky alkyl group, such as the tert‐butyl group, and with a phenyl group bearing either a strong electron‐withdrawing substituent, such as the 3‐nitrophenyl and 4‐nitrophenyl group, or an electron‐releasing substituent, such as the 4‐methylphenyl and 4‐methoxyphenyl group.     

Synthesis of Substituted Pyrrolo[3,4‐a]carbazoles

The cycloaddition between N‐protected 3‐{1‐[(trimethylsilyl)oxy]ethenyl}‐1H‐indoles and substituted maleimides (= 1H‐pyrrole‐2,5‐diones) yielded substituted pyrrolo[3,4‐a]carbazole derivatives bearing an additional succinimide (= pyrrolidine‐2,5‐dione) moiety either at C(5a) or C(10b) depending on the type of the protection group at the indole N‐atom. Derivatives substituted at C(10b) were isolated when the protection group, Me₃Si or Boc (^tBuOCO), was eliminated during the reaction (Schemes 2 and 3), whereas a substitution at C(5a) was observed when an electron‐withdrawing group, Tos (4‐MeC₆H₄SO₂) or pivaloyl (Me₃CCO), was not eliminated (Scheme 1). Complex results were found in reactions between 1‐(trimethylsilyl)‐3‐{1‐[(trimethylsilyl)oxy]ethenyl}‐1H‐indole, in contrast to formerly reported results (Scheme 3). Some derivatives of 1H,5H‐[1,2,4]triazolo[1′,2 : 1,2]pyridazino[3,4‐b]indole‐1,3(2H)‐dione were obtained from reactions with 4‐phenyl‐3H‐1,2,4‐triazole‐3,5(4H)‐dione (Scheme 2). All structures were established by spectroscopic data, by calculations, and one representative structure was confirmed by an X‐ray crystallographic analysis (Fig.). Finally, the formation of the different structure types was discussed, and compared with similar reactions reported in the literature.     

Synthesis of Asymmetrically Substituted Terpyridines by Palladium‐Catalyzed Direct C?H Arylation of Pyridine N‐Oxides

The synthesis of asymmetrically substituted 2,2′:6′,2′′‐terpyridines is reported. First, palladium‐catalyzed C? H arylation of pyridine N‐oxides with substituted bromopyridines gave 2,2′‐bipyridine N‐oxides, which were further arylated in a second step to form 2,2′:6′,2′′‐terpyridine N‐oxides. Yields of up to 77 % were obtained with N‐oxides bearing an electron‐withdrawing ethoxycarbonyl substituent in the 4‐position. Pd(OAc)₂ with either P(tBu)₃ or P(o‐tolyl)₃ was used as the catalyst. Cyclometalated complexes derived from Pd(OAc)₂ and these phosphines were also effective. K₃PO₄ as the base gave better results than K₂CO₃. Subsequent deoxygenation with H₂ and Pd/C as the catalyst gave the asymmetrically substituted 2,2′:6′,2′′‐terpyridines in near quantitative yield. This reaction sequence significantly reduces the number of steps required in comparison with known cross‐coupling methods and therefore allows convenient and scalable access to substituted terpyridines.     

Cationic organotin cluster [t‐Bu2Sn(OH)(H2O)]22+2OTf−‐catalyzed one‐pot three‐component syntheses of 5‐substituted 1H‐tetrazoles and 2,4,6‐triarylpyridines in water

The cationic organotin cluster [t‐Bu₂Sn(OH)(H₂O)]₂²⁺2OTf^? is easy to prepare and stable in air. The catalytic activity of [t‐Bu₂Sn(OH)(H₂O)]₂²⁺2OTf^? as a neutral organotin Lewis acid catalyst is probed through the one‐pot three‐component syntheses of 5‐substituted 1H‐tetrazoles from aldehydes, hydroxylamine hydrochloride and sodium azide, and of 2,4,6‐triarylpyridines from aromatic aldehydes, substituted acetophenones and ammonium acetate. The reactions proceed well in the presence of 1 mol% of [t‐Bu₂Sn(OH)(H₂O)]₂²⁺2OTf^? in water and provide the corresponding 5‐substituted 1H‐tetrazoles and 2,4,6‐triarylpyridines in good to excellent yields. The method reported has several advantages such as the catalyst being neutral, low catalyst loading and use of water as a green solvent.     

1,3‐Dipolar Cycloadditions of Ethyl 2‐Diazo‐3,3,3‐trifluoropropanoate to Alkynes and [1,5] Sigmatropic Rearrangements of the Resulting 3H‐Pyrazoles: Synthesis of Mono‐, Bis‐ and Tris(trifluoromethyl)‐Substituted Pyrazoles

The 1,3‐dipolar cycloadditions of ethyl 2‐diazo‐3,3,3‐trifluoropropanoate with electron‐rich and electron‐deficient alkynes, as well as the van Alphen? Hüttel rearrangements of the resulting 3H‐pyrazoles were investigated. These reactions led to a series of CF₃‐substituted pyrazoles in good overall yields. Phenyl‐ and diphenylacetylene proved to be unreactive, but, at high temperature, the diazoalkane and phenylacetylene furnished a cyclopropene derivative. As expected, the 1,3‐dipolar cycloaddition to the ynamine occurred much faster than those to electron‐deficient alkynes. With one exception, all cycloadditions proceeded with excellent regioselectivities. The [1,5] sigmatropic rearrangement of the primary 3H‐pyrazoles provided products with shifted acyl groups; products resulting from the migration of a CF₃ group were not detected. In agreement with literature reports, this rearrangement occurs faster with 3H‐pyrazoles bearing electron‐withdrawing substituents.     

Mechanism of (Salen)manganese(III)‐Catalyzed Oxidation of Aryl Phenyl Sulfides with Sodium Hypochlorite

The oxidation of 4‐substituted phenyl phenyl sulfides was carried out with several oxo(salen)manganese(V) complexes in MeCN/H₂O 9 : 1. The kinetic data show that the reaction is first‐order each in the oxidant and sulfide. Electron‐attracting substituents in the sulfides and electron‐releasing substituents in salen of the oxo(salen)manganese(V) complexes reduce the rate of oxidation. A Hammett analysis of the rate constants for the oxidation of 4‐substituted phenyl phenyl sulfides gives a negative ρ value (ρ=?2.16) indicating an electron‐deficient transition state. The log k₂ values observed in the oxidation of each 4‐substituted phenyl phenyl sulfide by substituted oxo(salen)manganese(V) complexes also correlate with Hammett σ constants, giving a positive ρ value. The substituent‐, acid‐, and solvent‐effect studies indicate direct O‐atom transfer from the oxidant to the substrate in the rate‐determining step.     

Reactivity of Hydroxy and Amino Derivatives of 2‐Phenyl‐1H‐imidazoline and 2‐Phenyl‐1H‐imidazole toward Isocyanates: Synthesis of Appropriate Carbamates and Ureas

Reactivity of 2‐(4‐hydroxyphenyl)‐1H‐imidazoline and 2‐(4‐hydroxyphenyl)‐1H‐imidazole toward substituted phenyl isocyanates was studied. When mentioned imidazoline was treated with 2.5 equiv of substituted phenyl isocyanate, three N,O‐dicarboxamides were prepared (substituents are H, 4‐NO₂, and 4‐CH₃). Subsequently, N,O‐diacetylated 2‐(4‐hydroxyphenyl)‐1H‐imidazoline was prepared and selective deprotection method was developed for preparation of 1‐acetyl‐2‐(4‐hydroxyphenyl)‐1H‐imidazoline using diethylamine in acetone. Six carbamates derived from this imidazoline were then prepared using 1.1 equiv of substituted phenyl isocyanates (substituents are H, 4‐CH₃, 4‐OCH₃, 4‐NO₂, 4‐CN, and 3‐CF₃). Finally, two carbamates were prepared from 2‐(4‐hydroxyphenyl)‐1H‐imidazole (substituents are 4‐NO₂ and 4‐CN). No reactivity to imidazole ring was observed in this case. Eight derivatives were subjected to antimycobacterial screening. Concurrently, reactivity of 2‐(2‐aminophenyl)‐ and 2‐(2‐hydroxyphenyl)‐1H‐imidazole toward aliphatic and aromatic isocyanates was studied. Eight ureas were prepared using equivalent mixture of 2‐(2‐aminophenyl)‐1H‐imidazole and isocyanate (Et, Pr, isoPr, terc‐Bu, Cy, Ph, 4‐CH₃C₆H₄, 4‐CNC₆H₄). Similar attempts to obtain related carbamates from 2‐(2‐hydroxyphenyl)‐1H‐imidazole lead only to three substituted phenyl carbamates (substituents are 4‐CH₃, 4‐NO₂, and 4‐CN). In both cases, no reactivity to imidazole ring was observed again.     

Synthesis of Mesoionic 4‐(para‐substituted Phenyl‐5‐2,4‐dichlorophenyl)‐1,3‐4‐thiadiazolium‐2‐aminides by Direct Cyclization via Acylation of Thiosemicarbazides

The synthesis of ten novel mesoionic 4‐[para‐substituted (H, CH₃, OCH₃, NO₂, Cl, Br, OH, t‐C₄H₉, C₆H₅, C₄H₉) phenyl‐5‐2,4‐dichlorophenyl]‐1,3‐4‐thiadiazolium‐2‐aminides, as hydrochlorides, are described. The synthesis strategy utilized the corresponding para‐substituted isothiocyanates as starting materials to obtain the thiosemicarbazides through reaction with phenylhydrazine (61–98%), which were then submitted to acylation with 2,4‐dichloro benzoyl chloride and direct cyclization to generate the desired substituted mesoionic compounds in good yields (ca. 80%).     

Two isostructural carboranes: 3‐phenyl‐1,2‐dicarba‐closo‐dodecaborane(12) and 1‐phenyl‐1,7‐dicarba‐closo‐dodecaborane(12)

Two phenyl‐substituted carboranes, 3‐phenyl‐1,2‐dicarba‐closo‐dodecaborane(12), C₈H₁₆B₁₀, (I), and 1‐phenyl‐1,7‐dicarba‐closo‐dodecaborane(12), C₈H₁₆B₁₀, (II), were found to be isostructural. Comparison of the bond angles at the ipso‐C atoms of the phenyl substituent for (I) and (II) [117.71 (3) and 118.45 (10)°, respectively] indicates that electron donation of the carborane cage for B‐ and C‐substituted carboranes is different.     

Copper(II)‐Catalyzed Synthesis of N‐Substituted‐3‐amino‐4‐cyano‐isoquinoline‐1(2H)‐ones by the Reaction of N‐Substituted‐2‐iodobenzamides with Malononitrile

A novel Cu(OAc)₂·H₂O catalyzed coupling reaction of N‐substituted‐2‐iodobenzamides with malononitrile to afford N‐substituted‐3‐amino‐4‐cyano‐isoquinoline‐1(2H)‐ones is described. The reaction proceeded in DMSO at 90°C for 5 h in nitrogen without external ligands.     

Iminopyrrole derivatives containing electron‐withdrawing substituents: the formation of dimers and supramolecular arrangements

The crystal structures of two p‐substituted phenylformiminopyrrole derivatives, namely 2‐[(4‐fluorophenyl)iminomethyl]pyrrole, C₁₁H₉FN₂, (1), and 2‐[(1H‐pyrrol‐2‐ylmethylidene)amino]benzonitrile, C₁₂H₉N₃, (2), bear F and C[triple‐bond]N electron‐withdrawing groups, respectively. Both structures feature two independent molecules in the asymmetric unit forming dimers via N—H...N hydrogen bonds. In the case of (1), each dimer interacts with two other dimers via C—H...F contacts, thus forming one‐dimensional chains in the b direction, whereas in the case of (2), a weak C—H...N interaction connects the dimers in one‐dimensional chains in the (110) direction.     

Density functional study of the relative reactivity in the concerted 1,3‐dipolar cycloaddition of nitrile ylide to disubstituted ethylenes

Density functional theory was used to perform a theoretical evaluation of (E)‐1,2‐disubstituted ethylenes as dipolarophiles for the 1,3‐dipolar cycloaddition reaction. The reactivities of electron‐withdrawing and ‐donating substituted ethylenes were examined by estimating their activation energies. The calculated activation energies predicted that the most reactive species is (E)‐1,2‐C₂H₂(NO)₂, whereas the least reactive is (E)‐2‐butene. Namely, it was demonstrated that 16‐electron 1,3‐dipole reactants with more electropositive substituents in terminal positions and ethylenes that possess more strongly electron‐withdrawing substituents facilitate 1,3‐dipolar cycloaddition reactions. All of the theoretical results can be rationalized using the configuration mixing model. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 83: 318–323, 2001     

4‐Phenyl‐1H‐imidazole (a low‐temperature redetermination), 1‐benzyl‐1H‐imidazole and 1‐mesityl‐1H‐imidazole

Low‐temperature studies of the simple variously substituted imidazole types 4‐phenyl‐1H‐imidazole, C₉H₈N₂, 1‐benzyl‐1H‐imidazole, C₁₀H₁₀N₂, and 1‐mesityl‐1H‐imidazole, C₁₂H₁₄N₂, extend comparisons between parent imidazole species and their derivatives, the pronounced double‐bond localization opposite the substituted N atom common to simple neutral species being redistributed aromatically on protonation.     

Gold(III) Chloride Catalyzed Synthesis of Chiral Substituted 3‐Formyl Furans from Carbohydrates: Application in the Synthesis of 1,5‐Dicarbonyl Derivatives and Furo[3,2‐c]pyridine

This report describes a gold(III)‐catalyzed efficient general route to densely substituted chiral 3‐formyl furans under extremely mild conditions from suitably protected 5‐(1‐alkynyl)‐2,3‐dihydropyran‐4‐one using H₂O as a nucleophile. The reaction proceeds through the initial formation of an activated alkyne–gold(III) complex intermediate, followed by either a domino nucleophilic attack/anti‐endo‐dig cyclization, or the formation of a cyclic oxonium ion with subsequent attack by H₂O. To confirm the proposed mechanistic pathway, we employed MeOH as a nucleophile instead of H₂O to result in a substituted furo[3,2‐c]pyran derivative, as anticipated. The similar furo[3,2‐c]pyran skeleton with a hybrid carbohydrate–furan derivative has also been achieved through pyridinium dichromate (PDC) oxidation of a substituted chiral 3‐formyl furan. The corresponding protected 5‐(1‐alkynyl)‐2,3‐dihydropyran‐4‐one can be synthesized from the monosaccharides (both hexoses and pentose) following oxidation, iodination, and Sonogashira coupling sequences. Furthermore, to demonstrate the potentiality of chiral 3‐formyl furan derivatives, a TiBr₄‐catalyzed reaction of these derivatives has been shown to offer efficient access to 1,5‐dicarbonyl compounds, which on treatment with NH₄OAc in slightly acidic conditions afforded substituted furo[3,2‐c]pyridine.     

Bis(tert‐butyl­sulfonyl)ethyne and 1‐tert‐butyl­sulfinyl‐2‐tert‐butyl­sulfonyl­ethyne

The title compounds are electron‐poor ethynes. The structure determination of bis­(tert‐butyl­sulfonyl)ethyne, C₁₀H₁₈O₄S₂, (I), is the first of a bis‐sulfonyl‐substituted ethyne. The mol­ecule is situated on a crystallographic inversion centre. The S—Csp bond [1.737 (2) Å] is the longest of this type reported to date. 1‐tert‐Butyl­sulfinyl‐2‐tert‐butylsulfonyl­ethyne, C₁₀H₁₈O₃S₂, (II), which is basically the same as (I) minus one O atom, crystallizes isomorphous with (I). This results in a nearly equal distribution of the three O atoms over the four possible positions.