Two‐Step Synthesis of 1,3‐Disubstituted 3,4‐Dihydro‐4‐thioxoquinazolin‐2(1H)‐ones from 1‐Bromo‐2‐fluorobenzenes

An efficient synthesis of 3‐alkyl‐3,4‐dihydro‐4‐thioxobenzoquinazolin‐2(1H)‐ones 3 has been accomplished in two steps and in satisfactory yields from 1‐bromo‐2‐fluorobenzenes 1 . Thus, the reaction of 1‐fluoro‐2‐lithiobenzenes, generated by the Br/Li exchange between 1 and BuLi, with alkyl isothiocyanates, gives N‐alkyl‐2‐fluorobenzothioamides 2 , which, in turn, react with a series of isocyanates in the presence of NaH to give the desired products 3 .     

Potassium Thiocyanate‐Promoted One‐Pot Synthesis of (1,3‐Diaryl‐2,5‐dioxoimidazolidin‐4‐ylidene)acetates from Aryl Isocyanates and Alkyl Propiolates. Short Communication

The reaction of aryl isocyanates and alkyl propiolates (=alkyl prop‐2‐ynoates) in the presence of potassium thiocyanate (KSCN) led to geometric isomers of alkyl 2‐(1,3‐diaryl‐2,5‐dioxoimidazolidin‐4‐ylidene)acetates in moderate‐to‐good yields.     

Organocatalytic Stereoselective Synthesis of 3‐Alkyl‐3‐hydroxy‐2‐oxindoles Catalyzed by Novel Water‐compatible Axially Unfixed Biaryl‐based Bifunctional Organocatalysts

In this work, six novel axially unfixed biaryl‐based water‐compatible bifunctional organocatalysts were designed and synthesized for the organocatalytic access to a variety of 3‐alkyl‐3‐hydroxy‐2‐oxindole derivatives via aldol reactions in water. Organocatalyzed by 5a , the direct aldol reactions of isatins with enolisable ketones underwent readily in water, furnishing the structurally diverse 3‐alkyl‐3‐hydroxy‐2‐oxindoles in various stereoselectivities (up to>99% dr and >99% ee). Moreover, a plausible transition state of the conducted aldol reactions was hypothesized to shed light on the observed stereoselectivities of the obtained 3‐alkyl‐3‐hydroxy‐2‐oxindoles.     

Comparative study of self‐assembly of a range of monofunctional aliphatic molecules on magnetron‐sputtered aluminium

The adsorption of a range of organic molecules from toluene onto the oxidized surface of magnetron‐sputtered aluminium metal is studied using sessile drop water contact angle measurements. Molecules with different head group functionalities and various chain lengths are considered, including alkyl carboxylic acids, alkyl phosphonic acids, alkyl amines, alkyl trimethoxysilanes, alkyl trichlorosilanes and epoxy alkanes. Alkyl phosphonic and carboxylic acids are identified as readily forming the most well‐packed monolayers on the aluminium surface, whereas the others adsorb less well and the chlorosilanes polymerize as a result of combination with moisture to form a thick deposit. The high‐adsorption‐density monolayers of alkyl phosphonic and carboxylic acids were studied using polarization modulation infrared reflection–absorption spectroscopy (PM‐IRRAS) and x‐ray photoelectron spectroscopy (XPS): PM‐IRRAS reveals relatively poorer ordering of the C₁₀ alkyl carboxylic acid monolayer compared with that formed from the phosphonic acid, and XPS data suggest that this is likely to relate to a lower ability to displace preadsorbed volatile organic compounds. Copyright © 2004 John Wiley & Sons, Ltd.     

A Simple One‐Pot Synthesis of N‐Alkyl‐2,5‐diaryl‐1,3‐dioxol‐4‐amines

An efficient procedure for the synthesis of N‐alkyl‐2,5‐diaryl‐1,3‐dioxol‐4‐amines 3 via a one‐pot reaction of aromatic aldehydes 2 and alkyl isocyanides 1 at room temperature in good yields is described (Scheme 1, Table).     

Reduction of 3‐Acyl Derivatives of Oxindoles,Benzo[b]furan‐2‐ones,and Benzo[b]thiophen‐2‐ones to the Corresponding Alkyl Derivatives by Sodium Borohydride–Acetic Acid

It was found that 3‐acyl derivatives of oxindoles, benzo[b]furan‐2‐ones, and benzo[b]thiophen‐2‐ones could be efficiently and conveniently reduced to the corresponding alkyl derivatives by pelletized sodium borohydride in acetic acid. A typical procedure involves heating the acylated substrates for approximately 90 min in a slurry of glacial acetic acid and sodium borohydride to provide the 3‐alkyl product in yields ranging from 62% to 96%. This synthetic methodology represents a convenient approach to the synthesis of the alkyl derivatives.     

Efficient One‐pot Synthesis of Alkyl 3‐(alkyl)‐4‐methyl‐2‐thioxo‐2,3‐dihydrothiazole‐5‐carboxylates in a Multi Component Reaction

A simple and efficient one‐pot synthesis of alkyl 2‐(alkyl)‐4‐methyl‐2‐thioxo‐2,3‐dihydrothiazole‐5‐carboxylates from the reaction of primary alkylamines and carbon disulfide in the presence of 2‐chloro‐1,3‐dicarbonyl compounds is described. This new protocol has several advantages such as lack of necessity of the catalyst, good yields, mild conditions and short times for reaction.     

Practical Synthesis of N‐Alkyl‐N‐alkyloxycarbonylaminomethyl Prodrug Derivatives of Acetaminophen,Theophylline, and 6‐Mercaptopurine

We report a novel synthesis of N‐alkyl‐N‐alkyloxycarbonylaminomethyl (NANAOCAM) prodrugs of acetaminophen, theophylline, and 6‐mercaptopurine by alkylation of the corresponding drug molecule with N‐alkyl‐N‐alkyloxycarbonylaminomethyl chlorides in good yield. Most of the alkylating agents were efficiently synthesized by chloromethylation of N‐alkyl carbamic acid alkyl esters, which in turn were made from alkyl amines and alkyl chloroformates. In cases where the alkyl chloroformates were not available, synthesis of N‐alkyl carbamic acid alkyl esters was accomplished by converting an alcohol to a chloroformate or to an activated acylating agent such as acyl imidazoles or p‐nitrophenylcarbonate esters, followed by their reaction with alkyl amines.     

A Diastereoselective Synthesis of Functionalized Tetrahydroindeno[2′,1′,3,4]pyrido[2,1‐a]isoquinolines

An effective route to alkyl 9a‐(2,3‐dihydro‐1,3‐dioxo‐1H‐inden‐2‐yl)‐9a,14,14a,14b‐tetrahydro‐14‐oxoindeno[2′,1′:3,4]pyrido[2,1‐a]isoquinoline‐9‐carboxylates via a diastereoselective one‐pot four‐component reaction of isoquinoline and alkyl prop‐2‐ynoates with two equivalents of indane‐1,3‐dione, in aqueous MeOH at room temperature, is described.     

One‐Pot Synthesis of Pentaalkyl 7‐[(Alkylamino)carbonyl]‐2‐oxa‐1‐azabicyclo[3.2.0]hept‐3‐ene‐3,4,5,6,7‐pentacarboxylate

Dialkyl acetylenedicarboxylates react with alkyl 2‐nitroethanoates in the presence of alkyl isocyanides in a one‐pot reaction to afford the title compounds in 78–90% yield.     

New Approaches to the Synthesis of 4‐(2‐Aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones and 3‐Ureidoindoles and a Study of Their Interconversion

3‐Alkyl/aryl‐3‐ureido‐1H,3H‐quinoline‐2,4‐diones ( 2 ) and 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) react in boiling concentrated HCl to give 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ). The same compounds were prepared by the same procedure from 2‐alkyl/aryl‐3‐ureido‐1H‐indoles ( 4 ), which were obtained from the reaction of 3‐alkyl/aryl‐3‐aminoquinoline‐2,4(1H,3H)‐diones ( 1 ) with 1,3‐diphenylurea or by the transformation of 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) and 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ) in boiling AcOH. The latter were converted into 1,3‐bis[2‐(2‐oxo‐2,3‐dihydro‐1H‐imidazol‐4‐yl)phenyl]ureas ( 5 ) by treatment with triphosgene. All compounds were characterized by ¹H‐ and ¹³C‐NMR and IR spectroscopy, as well as atmospheric pressure chemical‐ionisation mass spectra.     

Cesium Carbonate–Promoted Michael‐Type Addition of Thiols to Hex‐1‐en‐3‐ulose: A Practical Synthesis of 2‐Deoxy‐1‐thio‐α‐hexopyranosid‐3‐ulose Template

The template 2‐deoxy‐1‐thio‐α‐hexopyranosid‐3‐ulose was synthesized in quantitative yield and high diastereoselectivity by 1,4‐addition of aryl and alkyl thiols to hex‐1‐en‐3‐ulose promoted by cesium carbonate in THF.     

Synthesis of Functionalized Pyrroles by Reaction of 3,4‐Diacetylhexane‐2,5‐dione with Primary Amines in Water

3,4‐Diacetylhexane‐2,5‐dione (tetra‐acetylethane) undergoes a complex reaction with primary amines in boiling water to produce N‐alkyl‐3‐acetyl‐2,5‐dimethylpyrroles, together with small quantities of N‐alkyl‐3,4‐diacetyl‐2,5‐dimethylpyrroles and 2,5‐dimethyl‐1H‐pyrrol‐3‐yl‐vinyl‐acetamides. When the reaction was carried out in methanol at room temperature, the yields of the latter products increased.     

Computational Insight into Nickel‐Catalyzed Carbon–Carbon versus Carbon–Boron Coupling Reactions of Primary,Secondary, and Tertiary Alkyl Bromides

The nickel‐catalyzed alkyl–alkyl cross‐coupling (C?C bond formation) and borylation (C?B bond formation) of unactivated alkyl halides reported in the literature show completely opposite reactivity orders in the reactions of primary, secondary, and tertiary alkyl bromides. The proposed Ni^I/Ni^III catalytic cycles for these two types of bond‐formation reactions were studied computationally by means of DFT calculations at the B3LYP level. These calculations indicate that the rate‐determining step for alkyl–alkyl cross‐coupling is the reductive elimination step, whereas for borylation the rate is determined mainly by the atom‐transfer step. In borylation reactions, the boryl ligand involved has an empty p orbital, which strongly facilitates the reductive elimination step. The inability of unactivated tertiary alkyl halides to undergo alkyl–alkyl cross‐coupling is mainly due to the moderately high reductive elimination barrier.     

Preparation of Alkyl Carbamate of 1‐Protected Indole‐3‐methylamine as a Precursor of Indole‐3‐methylamine

A series of alkyl carbamates 3 of 1‐protected indole‐3‐methylamines, alkyl carbamates 6 of thiophenylmethylamines, and pyrrolylmethylamines were prepared from the corresponding acetamides 2 and 5 in good to excellent yields via diacetoxyiodobenzene‐promoted Hofmann rearrangement. For a successful Hofmann rearrangement, an electron‐withdrawing group on position 1 of indolylacetamide and pyrrolylacetamide was required. The alkyl carbamate 3g was demonstrated to serve well as a stable precursor of 1‐protected indole‐3‐methylamine 1.     

Synthesis of Novel Alkyl‐Sulfanyl 1,3,4‐Oxadiazolyl‐1,3,5,7‐Tetraazatricyclic Ammonium Chloride Type Cationic Surfactants

A series of novel cationic surfactants bearing 1,3,4‐oxadiazole and tetraazatricyclic ring structures were synthesized by alkyl chain elongation of 5‐{10‐[4‐(hydroxymethyl)phenoxy]decyl}‐2,3‐dihydro‐1,3,4‐oxadiazole‐2‐thione with homologous series of alkyl bromides, followed by chlorination of the corresponding benzyl alcohols with thionyl chloride and quaternization of the obtained intermediates with hexamethylenetetramine.     

Synthesis and Bioactivity of Some New 2-(Alkoxy carbonyl alkyl)-6-bromo-3,4-dihydro-3-(α-methyl benzyl)-2-oxo- benzo[e] [2H-1,3,2-oxazaphosphinine] Derivatives

Synthesis of some new 2-(alkoxy carbonyl alkyl)-6-bromo-3,4-dihydro-3-(α-methyl benzyl)-2-oxo-3-benzo- [e][2H-1,3,2-oxazaphosphinine] derivatives was accomplished through a two step process, which involves the condensation of 2-[(α-methylbenzyl amino)methyl]-4-bromophenol (1) with phosphorus oxychloride in equimolar quantities in the presence of triethylamine in dry toluene in 50—55 ℃ producing the corresponding intermediate (2), and subsequent reaction with the amino acid alkyl ester in dry tetrahydrofuran in the presence of triethylamine at different temperatures. They exhibited significant antibacterial and fungal activity.     

An Efficient Synthesis of 14‐Aryl or Alkyl‐14H‐Dibenzo[a. j]Xanthenes Using Reusable HBF4‐SiO2 Catalyst Under Thermal and Solvent‐Free Conditions

A simple and convenient procedure for the synthesis of 14‐aryl or alkyl‐14H‐dibenzo[a. j]xanthene derivatives is described through a one‐pot condensation of β‐naphthol with various aryl or alkyl aldehydes in the presence of HBF₄‐SiO₂ as the catalyst under thermal and solvent‐free conditions.     

Synthesis of Novel Aryloxy Propanoyl Thiadiazoles as Potential Antihypertensive Agents

2‐Amino‐5‐aryl/alkyl‐1,3,4‐thiadiazoles 3a‐e were synthesized from aliphatic and aromatic acids and thiosemicarbazide. These 2‐amino‐5‐aryl/alkyl‐1,3,4‐thiadiazoles 3a‐e were condensed with 2‐(naphthalenyloxymethyl) oxirane 4a‐b to prepare some naphthalenyloxy‐propanol amine derivatives 5a‐j . These compounds were synthesized as potential antihypertensive agents.     

Zinc‐Catalyzed Borylation of Primary,Secondary and Tertiary Alkyl Halides with Alkoxy Diboron Reagents at Room Temperature

A new catalytic system based on a Zn^II NHC precursor has been developed for the cross‐coupling reaction of alkyl halides with diboron reagents, which represents a novel use of a Group XII catalyst for C? X borylation. This approach gives borylations of unactivated primary, secondary, and tertiary alkyl halides at room temperature to furnish alkyl boronates, with good functional‐group compatibility, under mild conditions. Preliminary mechanistic investigations demonstrated that this borylation reaction seems to involve one‐electron processes.