Controllable Regioselective Acylation of Flavonoids Catalyzed by Lipase in Microreactors

A method for regioselective acylation of flavonoids (naringin and naringin dihydrochalcone) in a flow microreactor using Lipozyme TL IM from Thermomyces lanuginosus as the catalyst has been developed. The important features of this method include mild reaction conditions, short reaction times (30 min), high yields, and high regioselectivities.     

CARBON-PHOSPHORUS HETEROCYCLES. SYNTHESIS OF SUBSTITUTED 2,3,4,5-TETRAHYDRO-5-OXO-2,2-DIPHENYL-1H-2-BENZOPHOSPHEPINIUM SALTS VIA INTRAMOLECULAR ACYLATION WITH 115% POLYPHOSPHORIC ACID

Abstract

Intramolecular acylation involving three ω-carboxyalkylphosphonium salts 1a-c has been achieved in the presence of 115% polyphosphoric acid (PPA) to yield the heretofore unknown 2,3,4,5-tetrahydro-5-oxo-2,2-diphenyl-1H-2-benzo-phosphepinium salts 2a-c. The open-chain precursors were easily prepared by quaternization of the corresponding tertiary arylmethyl-substituted phosphines with 3-chloropropanoic acid. Cyclization of the carboxy-substituted salts was accomplished at 200°C with PPA in modest yields (37–64%). A mechanism reminiscent of a classic electrophilic acylation process was tentatively proposed. An x-ray crystallographic analysis of a single crystal of 2a showed the phosphepin ring to exist in a twisted-chair conformation.     

Preparation of Mg–Al hydrotalcite from the effluent of Friedel–Crafts reaction and its application as a catalyst in Knoevenagel reaction

Abstract

Hydrotalcite containing magnesium and aluminium (Mg–Al HT) with a molar ratio of Mg(II)/Al(III) = 2.5 has been prepared by a co-precipitation method using the effluent of a Friedel–Crafts acylation reaction. The HT was calcined at 500°C and reconstructed with deionized water. The synthesized HT was characterized by XRD and FT-IR spectroscopy and was successfully used as a catalyst in the Knoevenagel reaction of aldehydes and active methylene compounds. The catalyst was found to be reusable.     

Hafnium inspired activation of highly hindered anhydrides in the acylation of alcohols and polyols

A novel and highly efficient method for activating highly hindered acid anhydrides towards the acylation of alcohols and carbohydrate-derived polyols has been developed. This new method relies on the capacity of the hafnium triflate catalyst Hf(OTf)₂ to activate highly hindered acid anhydrides, and to direct the acylation reaction. This new acylation protocol is mild and proceed at room temperature with low catalyst loading. The method is versatile and has been extended to different alcohol substrates with different steric encumbrance as well as carbohydrate-derived polyols to afford the corresponding ester products in good to excellent yields.     

Isolation and Synthesis of Dibenzocyclooctadiene Lignans: (±)‐Schizandrin and Its Analogues

Simple isolation of (±)‐schizandrin (1) and preparation of its analogues (6–8) via acylation of (±)‐schizandrin (1) are described. The key strategy in the synthesis involves the catalytic acylation reaction of 1 with several acylating reagents.     

Phosphine-Free Suzuki Cross-Coupling Reaction Using an Efficient and Reusable Pd Catalyst in an Aqueous Medium Under Microwave Irradiation

Abstract

We report here an improved, highly efficient, and general method for the ligand-free Suzuki cross-coupling reaction to the synthesis of biaryls, bipyridyls, thienylpyridine, and allylphenols. Microwave irradiation of (het)aryl halides and (hetaryl, allyl)arylboronic acid N-methyl-iminodiacetic acid (MIDA) ester, using polyurea microencapsulated palladium catalyst (Pd EnCat 30), gave the coupling adducts 1a–x in excellent yields in just 10–18 min.     

Synthesis of New Pyrazolo[1,5-α]quinazoline Derivatives

The reaction of various anthranilic acid derivatives or their esters with 4-oxotetrahydrothiophene-3-carbonitrile 2, 2-oxocyclopentanecarbonitrile (9, n = 1) or 2-oxocyclohexanecarbonitrile (9, n = 2) in ethanol under reflux conditions giving rise the formation of single products isolated in each case after simple filtration. The products were characterized as pyrazolo[1,5-a]quinazolin-5-ones 4 instead of the expected pyrazol-3-amines 3. These cascade condensation–intramolecular acylation processes generated in one-step reactions from simple starting materials novel heterocyclic scaffolds ready for further functionalization. The present synthetic protocol provides acceptable yields of new tetracyclic products in high purity.     

Microwave‐Assisted NiCl2 Promoted Acylation of Alcohols

Abstract

A microwave oven acylation of alcohols by carboxylic acid anhydrides has been developed. NiCl₂ has been proven an efficient catalyst for the acylation of primary, secondary, and tertiary alcohols and phenols under microwave conditions.     

One‐Step Reaction of Friedel–Crafts Acylation and Demethylation of Aryl‐Methyl Ethers Catalyzed by Ytterbium(III) Triflate

Abstract

Catalytic amount of ytterbium(III) triflate [Yb(OTf)₃] has been used to catalyze Friedel–Crafts acylation and demethylation of aryl‐methyl ethers in one‐step reaction to produce hydroxyacylphenones with moderate yields under mild conditions.     

SELECTIVE ALKYLATION/ACYLATION OF DI- OR TRIANIONS: EXPEDITIOUS DERIVATIZATION OF ENDOTHELIN ANTAGONISTS[1]

ABSTRACT

Sitaxsentan sodium (1, TBC11251Na) is an ET_A selective endothelin antagonist under clinical development for pulmonary arterial hypertension and congestive heart failure. Second generation compounds, as exemplified by TBC2576 (2) are currently under development in our laboratories. To rapidly access analogs of 1 and 2, a route was developed for the selective alkylation or acylation of the corresponding di- or trianions derived from these two highly functionalized compounds. We report here on this straightforward, yet effective, procedure consisting of treating the di- or trianions with an excess amount of electrophiles, followed by a rapid quench. In this manner, selective alkylation or acylation of 1 and 2 was achieved with satisfactory yields.     

ACYLATION OF AROMATIC COMPOUNDS USING MOISTURE INSENSITIVE MESOPOROUS Si-MCM-41 SUPPORTED Ga2O3 CATALYST

ABSTRACT

Mesoporous Si-MCM-41 supported Ga₂O₃ is a highly active catalyst for the acylation of aromatic compounds with different acyl chlorides. Moreover, this catalyst is not deactivated by water and hence does not require moisture-free reaction conditions.     

4‐(N,N‐Dimethylamino)pyridine‐Embedded Nanoporous Conjugated Polymer as a Highly Active Heterogeneous Organocatalyst

We report herein for the first time the incorporation of a versatile organocatalyst, 4‐(N,N‐dimethylamino)pyridine (DMAP), into the network of a nanoporous conjugated polymer (NCP) by the “bottom‐up” approach. The resulting DMAP‐NCP material possesses highly concentrated and homogeneously distributed DMAP catalytic sites (2.02 mmol g^?1). DMAP‐NCP also exhibits enhanced stability and permanent porosity due to the strong covalent linkage and the rigidity of the “bottom‐up” monomers. As a result, DMAP‐NCP shows excellent catalytic activity in the acylation of alcohols with yields of 92–99 %. The DMAP‐NCP catalyst could be easily recovered from the reaction mixture and reused in at least 14 consecutive cycles without measurable loss of activity. Moreover, the catalytic acylation reaction could be performed under neat and continuous‐flow conditions for at least 536 h of continuous work with the same catalyst activity.     

Friedel–Crafts Acylation and Related Reactions Catalyzed by Heteropoly Acids

The Friedel–Crafts acylation of anisole (AN) with acetic anhydride (AA) and the Fries rearrangement of phenyl acetate in the liquid phase catalyzed by bulk and silica-supported heteropoly acids (HPA), mainly H₃PW₁₂O₄₀ (PW), have been studied. In anisole acylation, PW exhibits very high activity, yielding up to 98% para and 2–4% ortho isomer of methoxyacetophenone (MOAP) at 90-110°C and an AN/AA molar ratio of 10–20. The reaction appears to be heterogeneously catalyzed; no contribution of homogeneous catalysis by HPA was observed. PW is almost 100 times more active than the zeolite H-Beta, which is in agreement with the higher acid strength of HPA. The PW catalyst is reusable, although gradual decline of activity was observed due to the coking of the catalyst. The acylation is inhibited by the product because of adsorption of MOAP on the catalyst surface. In contrast to anisole, the acylation of toluene with HPA is far less efficient than that with H-Beta. Evidence is provided that the activity of HPA in toluene acylation is inhibited by preferential adsorption of acetic anhydride on the catalyst. It is demonstrated that PW is a very efficient and reusable catalyst for the Fries rearrangement of phenyl acetate in homogeneous or heterogeneous liquid-phase systems at 100–150°C.     

MoO2Cl2 as a novel catalyst for Friedel-Crafts acylation and sulfonylation

The use of MoO₂Cl₂ as a novel catalyst for Friedel-Crafts acylation and sulfonylation is described. A series of aromatic ketones and sulfones were prepared in moderate to good yields using acyl chloride or sulfonyl chloride in the presence of MoO₂Cl₂ (20 mol %), under solvent-free conditions.     

Hydrogenation/Regioselective C‐Acylation Reaction of Diethyl Coumarin‐3‐phosphonate With NaBH4/Acid Anhydrides: A New One‐Pot Tandem Reaction

The one‐pot tandem reaction of diethyl coumarin‐3‐phosphonate 1 with a mixture of sodium borohydride/acid anhydrides gives mainly the corresponding hydrogenation/acylation product of diethyl 3‐acyl‐2‐oxochroman‐3‐ylphosphonates 3a–d in good yields. Different experimental conditions have been examined to get the best yields of the reaction products. From this reaction the hydrogenation product of diethyl 2‐oxochroman‐3‐ylphosphonate, 2, as well as the products of the consecutive hydrogenation, diethyl 2‐hydroxychroman‐3‐ylphosphonate (4) and diethyl 3‐[2‐hydroxyphenyl]‐1‐hydroxy‐propan‐2‐ylphosphonate (5), have been isolated.     

Synthesis of 5-(dimethylsilyl)pentylalkylferrocene-grafted HTPB (alkylFc-HTPB) via platinum-catalyzed hydrosilylation

In this work, at first alkylferrocene derivatives were synthesized according to procedure described in the literature. (5-Chloropentanoyl)ferrocene derivatives were prepared by Friedel–Crafts acylation of ferrocene and alkylferrocene derivatives with 5-chloropentanoyl chloride in dichloromethane, and AlCl₃ was used as catalyst. The corresponding 5-chloropentylferrocene derivatives were synthesized from reduction of these products by NaBH₄ in diglyme at 0 °C. Finally (5-alkylferrocenylpentyl)dimethylsilane was synthesized from reaction of 5-chloropentylferrocene derivatives with magnesium in THF and reaction of corresponding Grignard reagents with chlorodimethylsilane in 82–87% yields. ¹H and ¹³C NMR, FT-IR spectroscopy supported the predicted structure of the product. Nine samples of alkylferrocene-grafted hydroxyl-terminated polybutadiene (alkylFc-HTPB) derivatives, containing different percent of iron, were synthesized by hydrosilylation reaction of [5-(alkylferrocenyl)pentyl]dimethylsilane with hydroxy-terminated polybutadiene (HTPB), in the presence of catalytic amount of the hexachloroplatinic acid (Speier’s catalyst). FT-IR spectroscopy was utilized to follow the progress of the reaction, by monitoring the loss of the Si–H absorption at 2110 cm^?1, and the reaction was completed in 24 h. Some properties of resulting prepolymer like viscosity, glass transition temperature and iron percentage as important parameters in production of composite propellants were investigated. For example, the viscosity increased with increasing iron content because of the greater extent of ferrocene grafting in the polymer.     

Microwave-Assisted One-Pot Synthesis of Bioactive UGI-4CR Using Fluorite as Benign and Heterogeneous Catalyst

Fluorite has been used as an activating heterogeneous catalyst for a rapid and facile one-pot synthesis of biologically active Ugi four-component reaction (Ugi-4CR) under microwave irradiation in good to moderate yields with short reaction times. The catalyst is environmentally benign, commercially available, and reusable several times with no reduction in its efficiency. The resulting Ugi derivatives 5(a–h) were characterized on the basis of ¹H and ¹³C NMR, infrared, elemental analysis, and mass spectral data. The synthesized moieties were screened for their potential antibacterial activities in vitro against a few microorganisms: Staphylococcus aureus (Gram positive), Bacillus subtilis (Gram positive), Escherichia coli (Gram negative), and Proteus vulgaris (Gram negative). The screening data show that compounds 5a, 5c, 5e, and 5h are highly active against the strains.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Synthesis of 1′,3′-Dioxolan-2′-one by the Reaction of Steroidal Oxiranes with Carbon Dioxide: Synthesis of Five-Membered Cis Cyclic Carbonates

The reaction of 3β-acetoxy-5,6α-epoxy-5α-cholestane 1, its 3β-chloro analogue 2, and 5,6α-epoxy-5α-cholestane 3 with carbon dioxide gas in the presence of sodium bromide as catalyst with continuous stirring at 100 °C for 30 min affords selectively the corresponding 1′,3′,-dioxolan-2′-ones (steroidal cyclic cis-carbonates) 4–6 in excellent yields. The structures of these products have been established on the basis of their elemental analysis and spectral data (infrared, ¹H NMR, and mass).     

Solvent Affected Facile Synthesis of Hydroxynaphthyl Ketones: Lewis Acids Promoted Friedel–Crafts and Demethylation Reaction

Hydroxynaphthyl ketones were obtained with high yields under very mild conditions in the presence of AlCl₃ via Friedel–Crafts acylation and demethylation from naphthyl ethers. Several Lewis acids were tested, and AlCl₃ was the most efficient catalyst.     

Aluminum-catalyzed efficient synthesis of anilides by the acylation of aryl amines under ultrasonic conditions

Abstract

Substituted aryl amines undergo smooth acylation with different acyl chlorides to give anilides under sonic condition (35 kHz, 25°C) in the presence of catalytic amounts of aluminum metal powder in acetonitrile as solvent. All the reactions go to completion within 4 min and give the products in high yields (85–97%).