Preparation of Calix[4]arene Alkylamine Derivatives by Mannich Reaction and use as Phase-Transfer Catalysts for Esterification Reaction

In this study, 5,11,17,23-tetrakis[(N-ethylpiperazine)methyl]-25,26,27,28-tetrahydroxycalix[4]arene (3) and 5,11,17,23-tetrakis[(4-carboethoxy-N-piperidino) methyl]-25,26,27,28-tetrahydroxycalix[4]arene (4) were synthesized in one step according to the Mannich reaction by the treatment of calix[4]arene with a secondary amine (N-ethylpiperazine, ethyl-4-piperidincarboxylate) and formaldehyde. The calix[4]arene derivatives (3, 4) were characterized by a combination of FTIR, ¹H NMR and elemental analyses. The synthesized compounds were used in an esterification reaction as the phase transfer catalyst. The catalytic efficiency of the calix[4]arenes 3 and 4 was evaluated by carrying out the ester-forming reaction of alkali metal carboxylates (sodium butyrate or sodium caprylate) with p-nitrobenzyl bromide. It was observed that the ester-forming reaction of alkali metal carboxylates with p-nitrobenzyl bromide, using calix[4]arene-based catalyst 3 as a phase-transfer catalyst in dichloromethan, provided the best yields.     

Synthesis of 2-(2-methoxyethyl)- and 2-(2-thiomethoxyethyl)-aniline and related compounds

Summary 2-(2-Nitrophenyl)-ethanol (2) was methylated with dimethyl sulfate to give 2-(2-methoxyethyl)-1-nitrobenzene (3a) which then was reduced with hydrazine hydrate in the presence ofRaney nickel to 2-(2-methoxyethyl)-aniline (1a). Compound1a can be transformed into the N-monosilylated derivative4 by lithiation withn-butyllithium and subsequent reaction with chlorotrimethylsilane. Reaction of2 withp-toluenesulfonyl chloride yields 2-(2-nitrophenyl)-ethylp-toluenesulfonate (5), which reacts with sodium thiomethoxide to give 2-(2-nitrophenyl)-ethylp-toluenesulfonate (5), which reacts with sodium thiomethoxide to give 2-(2-thiomethoxyethyl)-1-nitrobenzene (3b).3b was reduced with hydrazine hydrate in the presence ofRaney nickel to yield 2-(2-thiomethoxyethyl)-aniline (1b). Ethyl (2-nitrophenyl)-acetate (6) could be dimethylated with methyl iodide in the presence of potassiumtert-butoxide and 18-crown-6 to give ethyl 2-methyl-2-(2-nitrophenyl)-propionate (7). Reduction of7 with lithium borohydride yields 2,3-dihydro-3,3-dimethyl-1H-indole (9) and 2-[(1-hydroxy-2-methyl)-2-propyl]-aniline (10).

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Synthese von 2-(2-Methoxyethyl)- und 2-(2-Thiomethoxyethyl)-anilin und verwandten Verbindungen

Zusammenfassung 2-(2-Nitrophenyl)-ethanol (2) wurde mit Dimethylsulfat zu 2-(2-Methoxyethyl)-1-nitrobenzol (3a) methyliert, das sich mit Hydrazinhydrat in Gegenwart vonRaney-Nickel zu 2-(2-Methoxyethyl)-anilin (1a) reduzieren läßt. Verbindung1a kann durch Metallierung mitn-Butyllithium und anschließende Reaktion mit Chlortrimethylsilan in dasN-monosilylierte Derivat4 umgewandelt werden. Reaktion von2 mitp-Toluolsulfonylchlorid ergab 2-(2-Nitrophenyl)-ethyl-p-Toluolsulfonat (5), das mit Natriumthiomethanolat zu 1-Nitro-2-(2-thiomethoxyethyl)-benzol (3b) reagiert.3b wurde mit Hydrazinhydrat in Gegenwart vonRaney-Nickel zu 2-(2-Thiomethoxyethyl)-anilin (1b) reduziert. Ethyl-2-(nitrophenyl)-acetat (6) kann mit Methyliodid in Gegenwart von Kalium-tert-butoxid und 18-Krone-6 zu Ethyl-2-methyl-2-(2-nitrophenyl)-propionat (7) dimethyliert werden. Reduktion von7 mit Lithiumborhydrid lieferte 2,3-Dihydro-3,3-dimethyl-1H-indol (9) und 2-[(1-Hydroxy-2-methyl)-2-propyl]-anilin (10).

     

Evidence of Hydrogen Bonding in Stabilizing the Cone Conformation of a Monoalkylated Calix[4]arene. X-ray Structure of 25-[2-(ethoxy-1-p-toluene-sulfonate)phenyl]-26,27,28-trihydroxy calix[4]arene

The synthesis of25-[2-(ethoxy-1-p-toluene-sulfonate)phenyl]-26,27,28-trihydroxy calix[4]arene3 as a byproduct of the preparation of 1,3-dialkylated25,27-di-[2-(ethoxy-1p-toluene-sulfonate)phenyl]-26,28-dihydroxy calix[4]arene 2 is reported. Compound 3 is a monoalkylatedcalix[4]arene in the cone conformation. The X-ray structure of 3 showed that this conformation is stabilized by intramolecular hydrogen bonding.     

Calix[4]arenes with 1,2- and 1,3-upper rim tetrathiafulvalene bridges

Herein we report the synthesis of several calix[4]arene derivatives with tetrathiafulvalene bridges at the upper rim. Calix[4]arene-tetrathiafulvalene (TTF) conjugates 4a–d, fixed in cone conformation and comprising two smaller 1,2-bridges, were prepared by cyclisation of tetrakis-chloromethylated calix[4]arene 1 with 2,3-dithiolates of TTFs. Larger calix[4]arene-TTF macrocycles 14 and 15, also in cone conformation, contain 1,3-bridges and were synthesised by cyclisation of 2,6- and 2,7-dithiolates of TTFs with bis-bromomethylated calix[4]arene 7. Redox properties of new calix[4]arene-TTF conjugates were characterised using cyclic voltammetry.     

Synthesis of （p-Formylphenyl）azo Calix[4]arenes

Five novel azo calix[4]arenes were reported. The p-aminobenzaldehyde was diazotized with sodium nitrite in aqueous hydrochloride solution. Mono-, bis-, tris- and tetrakis(p-formylphenyl)azo calix[4]arenes (including proximal and distal isomers) were obtained respectively by diazo-coupling in different molar ratio to calix[4]arene(1) under pH=7.5--8.5 at 0-5℃. All (p-formylphenyl)azo calix[4]arenes were characterized by ^1H NMR, ^13C NMR, IR, MS (ESIMS) spectroscopies and elemental analysis.     

Synthesis and tautomeric transformations of 2-(tert-butyl)-1,2,4-benzotriazine-3(2H)-thiones

Treatment of 2-(tert-butyl)-1,2,3,4-benzotetrazinium tetrafluoroborates with sodium thiocyanate afforded 2-(tert-butylazo)phenyl isothiocyanates 3, which exist in equilibrium with 2-(tert-butyl)-1,2,4-benzotriazine-3(2H)-thiones 3′. The equilibrium depends on the substituents R in the benzene ring: the percentage of the open isomer 3 is about 20% for R = H or Me; for R = Cl or Br, the equilibrium is completely shifted to cyclic isomer 3′. The equilibrium is slow on the time scale of the ¹H and ¹³C NMR experiments. For compounds 3a/3′a (R = H), the spectra at 24 °C show two sets of signals, while those at 0 °C contain only signals for isomer 3′a. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1192–1195, July, 2006.     

Synthesis and Characterization of Partially Substituted at Lower Rim Phosphorus Containing Calix(4)arenes

The synthesis and characterization of several new phosphorus-containing partially lower rim substituted derivatives of 5,11,17,23-tetra(t-butyl) calix(4)arene (I) and 5,11,17,23-tetra(t-octyl)calix(4)arene (II), namely 5,11,17,23-tetra(t-butyl)-25,27-dihydroxy-26,28-bis(diphenylphosphinoyl-oxy) calix(4)arene (IV); 5,11,17,23-tetra(t-butyl)-25-hydroxy-26,27,28-tris(tetramethyldiamido-phosphinoyl-oxy) calix(4)arene (Vb); 5,11,17,23-tetra(t-butyl)-25,27-dihydroxy-26,28-bis(dimethyl-phosphinoyl-methoxy) calix(4)arene (VI); 5,11,17,23-tetra (t-octyl)-25,27-dihydroxy-26,28-bis(dimethyl-phosphinoyl-methoxy) calix(4)arene (VII) are reported. The structure of the synthesized calix(4)arene derivatives are identified and confirmed by elemental analysis, IR, ¹H, ¹³C, ³¹P{¹H} NMR spectroscopy and mass spectrometry as and X-ray crystallographic analysis of 5,11,17,23-tetra(t-butyl)-25,27-dihydroxy-26,28-bis(dimethyl-phosphinoyl-methoxy) calix(4)arene VI. According to the NMR spectra, all calix(4)arenes are in cone conformation.     

Synthesis of Novel 2-(4-Oxo-3,4- Dihydroquinazolin-2-Ylsulfinylmethyl)-3H-Quinazolin-4-One

Abstract

Condensation of 2-mercapto-3H-quinazolin-4-one (1) with chloroacetic acid gave 4-oxo-3,4-dihydroquinazoline-2-yl-sulfanyl)-acetic acid (2) that with anthranilamide (3) gave 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanylmethyl)-3H-quinazolin-4-one (4). Oxidation of 4 with sodium hypochlorite in alkaline medium gave the novel product, 2-(4-oxo-3,4- dihydroquinazolin-2-ylsulfinyl methyl)-3H -quinazolin-4-one) (5). The entire sequences of reactions in this work have been carried out using eco-friendly solvents and green conditions.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Synthese und Reaktionsverhalten von 3-(Bis(alkylthio)methylen)-3H-isobenzofuran-1-on-und 2-(Bis(alkylthio)methylen)-3(2H)-benzofuranon-Derivaten

Summary 3(Bis(alkylthio)methylene)-3H-isobenzofuran-1-ones2a–e and 2-(bis(alkylthio)methylene)-3(2H)-benzofuranone derivatives4a–c are obtained by reaction of phthalides1a–d or 3(2H)-benzofuranone (coumaranone3), respectively, with carbon disulfide under basic conditions followed by alkylation. The reaction behaviour of the new compounds2 and4 is investigated. 2-((2-Dimethylthio-1-oxo)ethyl)benzoic acid N,N-dimethylamide (7a) and 2-((2-dimethylthio-1-oxo)ethyl)-benzoic acid 2-methylpiperidide (7b) are surprisingly formed instead of the methylthio substitution products by treatment of2a with the corresponding amine in the presence of aluminum chloride.

Herrn Professor Dr. Dr. h. c.Waldemar Adam zum 60. Geburtstag gewidmet     

Effective Synthesis of Polysubstituted Pyrroles from (E)-Dimethyl 2-(Bromomethyl)-3-(diethoxyphosphoryl) Fumarate

Methyl 1-alkyl-4-(diethoxyphosphoryl)-5-oxo-2,5-dihydro-1H-pyrroles-3-carboxylate 4 was synthesized from the reaction of dimethyl 2-(bromomethyl)-3-(diethoxyphosphoryl) fumarate 3- E and primary amines in good yields.     

Thermal and Catalytic Diels-Alder Reactions Between (2E)-4, 5,6-Tri-O-acetyl-2,3-dideoxy-aldehydo-D-erythro -Hex-2-Enose and Cyclopentadiene

Abstract

Thermal and catalytic reactions between (2E)-4,5,6-tri-O-acetyl-2,3-dideoxy- aldehydo- d-erythro-hex-2-enose (1) and cyclopentadiene led, in each case, to the four stereoisomeric 5-formyl-6-(1,2,3-tri-O- acetyl-d-erythro-triol-1-yl)bicyclo[2.2.1]hept-2-enes (2-5). The role of the catalysts is discussed, and the face selectivity is rationalized in terms of both steric and electrostatic arguments. Upon subsequent sodium borohydride reduction, iodination, and zinc reduction, the adducts 2-5 were converted to their respective primary alcohols 6-9, that could be separated by column chromatography. Sequential basic deacetylation, oxidative cleavage of the sugar side-chain with sodium metaperiodate, and reduction with sodium borohydride, yielded the previously known (5R,6R)- or (5S, 6S)-bis(hydroxymethyl)norbornene-diols 12 or 13, thus establishing the C-5 and C-6 absolute configurations of their synthetic precursors.     

Synthesis and Host Properties of (1,3)- p-tert-Butylcalix[5]crown-6 Derivatives Incorporating the 1,1'-Binaphthalene-2,2'-dioxy Subunit

Alkylation of p-tert-butylcalix[5]arene (1) with 2,2'-bis(5-tosyloxy-3-oxa-1-pentyloxy)-1,1'-binaphthalene ((±)-2) in the presence of CsF affords selectively racemic 1,3-bridged calix[5] [5]crown-6-triol 3, along with very small amounts of the (1,2)-bridged regioisomer 4. Compound 3 has been converted into tri-methoxy and tri--picolyloxy derivatives 5 and 6, respectively, by exhaustive alkylation with the appropriate electrophile and base. The direct separation of the enantiomers of racemates 3 and 6 was achieved by HPLC, using a chiral stationary phase (Chiralpak AD). Hosts 5 and 6 are able to selectively form 1 : 1 endo-cavity complexes with the linear RNH₃ ⁺ ions.     

Preparation and Structure of (E)-1-(3′-Hydroxy-2-Furanyl)-3-(3″-Hydroxy-4″-Methoxyphenyl)-2-Propen-1-One

Abstract

A facile procedure is presented for the synthesis of (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2- propen-1-one (6). Galactosylisomaltol (1) was condensed with isovanillin (2) under strong alkaline conditions at 25 [ddot]C to form (E)-1-(3′-O-β-D-galactopyranosyloxy-2′-furanyl)-3-(3″- hydroxy-4″-methoxyphenyl)-2-propen-1-one (4). (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2-propen-1-one (6) was obtained by acid hydrolysis of 4 in a 53.9% yield. This hetero-cyclic 2-propen-1-one was characterized on the basis of spectral data (IR and ¹H NMR), physicochemical properties, and conversion to a mono-O-acetyl derivative.     

Syntheses,crystal structures,and spectral properties of Mn(II) and Co(II) complexes with 3-(p-chlorophenyl)- 4-(p-methylphenyl)-5-(2-pyridyl)-1,2,4-triazole

Two new complexes, trans-[MnL₂(NCS)₂] (1) and trans-[CoL₂(H₂O)(EtOH)](ClO₄)₂?·?H₂O (2) with asymmetrical triaryltriazole ligands [L?=?3-(p-chlorophenyl)-4-(p-methylphenyl)-5-(2-pyridyl)-1,2,4-triazole], have been synthesized and characterized by elemental analysis, FT-IR, ESI-MS, and single-crystal X-ray diffraction. In the complexes each L adopts a chelating bidentate mode via the nitrogen of pyridyl and triazole. Both complexes have a similar distorted octahedral core with two NCS^? ions in the trans position in 1, while one H₂O and one EtOH are present in the axial sites in 2.     

Synthesis of Some 2-(3-Alkyl/aryl-5-trifluoromethylpyrazol-1-yl)-4-(coumarin-3-yl)thiazoles as Novel Antibacterial Agents

Abstract

Herein, we describe a one-pot synthesis of some novel 2-(3-alkyl/aryl-5-trifluoromethylpyrazol-1-yl)-4-(coumarin-3-yl)thiazoles (6) involving the reaction of 3-alkyl/aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazole-1-thiocarboxamides (3) with 3-bromoacetylcoumarins (5) in the presence of sodium carbonate in ethanol. Reaction of 3 with 5 in the absence of sodium carbonate, however, resulted in the formation of 2-(3-alkyl/aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles, which were subsequently dehydrated to 6 by refluxing in ethanol in the presence of sodium carbonate. The structure of the synthesized compounds (6) was confirmed by infrared (IR), mass, ¹H NMR, and ¹³C NMR spectra and elemental analysis data. Newly synthesized compounds (6) showed moderate to good activity against Gram-positive bacteria.     

A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

Synthesis and Structure of Hexa(Diethoxyphosphoryloxy)calix[6]arene

Abstract

Hexapodand 1, which contains six phosphoryl groups at the lower rim of the macrocycle, was synthesized by the reaction of calix[6]arene with diethylchlorophosphate and sodium hydride. The structure is confirmed by X-ray studies: C₆₆H₉₀O₂₄P₆, Pbca, a = 14.867 (4), b = 18.577 (4), c = 26.510(6), D_c = 1.265g/cm³, Z = 4, and R = 0.063 for the 4600 observed reflections. The molecule 1 exists in a centrosymmetrical flattened 1,2,3-alternate conformation, in which diametrically opposed benzene rings are parallel. Four phosphoryl groups are oriented away from the cycle, two other groups are self-included in the macrocycle cavity.     

The One Step Synthesis of 2-(2-Bromo-5- methoxyphenyl)-5-(3-arylidene)-1,3-thiazolo[3,2-b]- 1,2,4-triazol-6-(5H)-ones and the Evaluation of the Anticonvulsant Activity

A smooth one-step synthesis of 2-(2-bromo-5-methoxyphenyl)-5-(3-arylidene)-1,3-thiazolo[3,2-b]-1,2,4-triazol-6-(5H)-ones (4a–n) is described. The newly prepared compounds are characterized by analytical and IR, ¹ H NMR, ¹³ C NMR, and FABMS spectral analysis. A few compounds are screened for anticonvulsant activity. Compounds 4i and 4n exhibit promising anticonvulsant activity and are recommended for further studies.     

Resolving Agents. I. (R)-(-)-2-Amino-1-benzyloxybutane,a New Base for the Resolution of Racemic Acids

Treatment of the readily available (R)-(-)enantiomer of 2-aminobutan-1-ol 1 with sodium hydride followed by benzyl chloride afforded the O-benzyl base (R)-(-)-2. The latter was successfully used for the resolution of racemic α-methylsuccinic and α-bromosuccinic acids, as well as of the racemic α-benzylhemisuccinic esters 8 and 9 resectively.     

3-(羟基-p-甲磺酰苯甲撑基)-5-氯-2-吲哚酮-1-羧酰胺类化合物的合成及生物活性研究

为了寻找高效低毒的非甾体抗炎药物, 将5-氯-2-吲哚酮与氯甲酸苯酯经酯化及水解制得1-苯氧羰基-5-氯-2-吲哚酮, 在4-N,N-二甲氨基吡啶作用下与对甲磺酰基苯甲酰氯反应, 经酸化得1-苯氧羰基-3-[羟基-(p-甲磺酰基)苯甲撑基]-5-氯-2-吲哚酮(II₁), 最后与相应的胺(氨)反应, 经盐酸中和制得未见文献报道的目标化合物II₂～II₁₅, 其结构经IR, ¹H NMR, MS和元素分析确证. 二甲苯致小鼠耳肿胀模型测试显示II₁₀, II₁₁, II₁₅具有明显的抗炎活性; 角叉菜胶致大鼠足跖肿胀模型试验结果表明, II₁₀, II₁₁抗炎活性与双氯芬酸钠和替尼达普钠相当(P＞0.05); 其中II₁₁的胃肠道副作用显著小于双氯芬酸钠(P＜0.05)和替尼达普钠(P＜0.01).