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 .     

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.     

Efficient One‐Pot Synthesis of Alkyl 2‐(Dialkylamino)‐4‐phenylthiazole‐5‐carboxylates and Single‐Crystal X‐Ray Structure of Methyl 2‐(Diisopropylamino)‐4‐phenylthiazole‐5‐carboxylate

The reaction between secondary amines, benzoyl isothiocyanate, and dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates) in the presence of silica gel (SiO₂) led to alkyl 2‐(dialkylamino)‐4‐phenylthiazole‐5‐carboxylates in fairly high yields. The structures of the products were confirmed by their IR, ¹H‐ and ¹³C‐NMR, and mass spectra, and by a single‐crystal X‐ray structure determination.     

A Novel,One‐Pot Four‐Component Route to 2′‐Thioxo‐2′,3′‐dihydrospiro[indole‐3,6′‐[1,3]thiazin]‐2‐one Derivatives

An efficient route to 2′,3′‐dihydro‐2′‐thioxospiro[indole‐3,6′‐[1,3]thiazin]‐2(1H)‐one derivatives is described. It involves the reaction of isatine, 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ⁵‐phosphanylidene)ethan‐1‐one, and different amines in the presence of CS₂ in dry MeOH at reflux (Scheme 1). The alkyl carbamodithioate, which results from the addition of the amine to CS₂, is added to the α,β‐unsaturated ketone, resulting from the reaction between 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ⁵‐phosphanylidene)ethan‐1‐one and isatine, to produce the 3′‐alkyl‐2′,3′‐dihydro‐4′‐phenyl‐2′‐thioxospiro[indole‐3,6′‐[1,3]thiazin]‐2(1H)‐one derivatives in excellent yields (Scheme 2). Their structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses.     

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).     

Ultrasound‐Assisted Wittig Reaction: A Short,Efficient Synthesis of 2‐Methoxy‐6‐Alkyl‐1,4‐Benzoquinones

A short, efficient synthesis of 2‐methoxy‐6‐alkyl‐1,4‐benzoquinones is described. Ultrasound‐assisted Wittig reaction of alkyltriphenyl phosphonium bromides with o‐vanillin in basic aqueous conditions followed by reduction with Na/n‐BuOH gave 2‐methoxy‐6‐alkylphenols. Oxidation of 2‐methoxy‐6‐alkylphenols with Fremy's salt produced the title compounds.     

Three‐component One‐pot Synthetic Route to Functionalized N‐Phenyl‐ and N,N‐(1,4‐phenylene)‐2‐alkylimino‐2,3‐dihydrothiazoles under Mild,Solvent‐ and Catalyst‐free Conditions

A simple and efficient one‐pot synthesis of alkyl‐2‐(alkylimino)‐4‐methyl‐3‐phenyl‐2,3‐dihydrothiazole‐5‐carboxylate and dialkyl 3,3′‐(1,4‐phenylene)‐bis‐[2‐(alkylimino)‐4‐methyl‐2,3‐dihydrothiazole‐5‐carboxylate] derivatives from the reaction of phenylisothiocyanate (and also 1,4‐phenylene diisothiocyanate) and primary alkylamines 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 and solvent, good yields,mild conditions and short times for reaction.     

Efficient Synthesis of Trialkyl 3‐Phenylbuta‐1,3‐diene‐1,2,4‐tricarboxylates by a Novel One‐Pot Multicomponent Reaction

Alkyl 2‐nitroacetates 2 react with alkyl phenylpropiolates 1 in the presence of Ph₃P in a mechanistically novel reaction to afford trialkyl 3‐phenylbuta‐1,3‐diene‐1,2,4‐tricarboxylates in yields of 60–80% under neutral conditions.     

Synthesis of 2‐Oxopyridine‐Fused 1,3‐Diazaheterocyclic Compounds via a Three‐Component Reaction

An efficient and simple route for the preparation of 2‐oxopyridine‐fused 1,3‐diazaheterocyclic compounds via a three component reaction is described. It involves the reaction between alkylenediamines 1 , 1,1‐bis(methylsulfanyl)‐2‐nitroethene, and alkyl prop‐2‐ynoates 2 in refluxing THF (Table). The structures were corroborated by spectroscopic (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and elemental analyses. A plausible mechanism for this type of cyclization is proposed (Scheme).     

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.     

One‐Pot Synthesis of 3‐Alkoxy‐2,3‐dihydro‐1H‐isoindol‐1‐ones by the Reactions of 2‐(Azidomethyl)benzoates with NaH

A new and facile method for the general preparation of 3‐alkoxy‐2,3‐dihydro‐1H‐isoindol‐1‐ones has been developed. Thus, the reaction of 2‐(azidomethyl)benzoates with NaH affords, after workup with H₂O, 3‐alkoxy‐2,3‐dihydro‐1H‐isoindol‐1‐ones 2 . 2‐Substituted 3‐alkoxy‐2,3‐dihydro‐1H‐isoindol‐1‐ones 4 can be obtained by adding alkyl halides prior to workup with H₂O.     

Isocyanide‐Based Three‐Component Synthesis of Highly Substituted 1,6‐Dihydro‐6,6‐dimethylpyrazine‐2,3‐dicarbonitrile, 3,4‐Dihydrobenzo[g]quinoxalin‐2‐amine,and 3,4‐Dihydro‐3,3‐dimethyl‐quinoxalin‐2‐amine Derivatives

A novel and efficient isocyanide‐based multicomponent reaction between alkyl or aryl isocyanides 1 , 2,3‐diaminomaleonitrile ( 2 ), naphthalene‐2,3‐diamines ( 6 ) or benzene‐1,2‐diamine ( 9 ), and 3‐oxopentanedioic acid ( 3 ) or Meldrum's acid ( 4 ) or ketones 7 was developed for the ecologic synthesis, at room temperature under mild conditions, of 1,6‐dihydropyrazine‐2,3‐dicarbonitriles 5a – 5f in H₂O without using any catalyst, and of 3,4‐dihydrobenzo[g]quinoxalin‐2‐amine and 3,4‐dihydro‐3,3‐dimethyl‐quinoxalin‐2‐amine derivatives 8a – 8g and 10a – 10e , respectively, in the presence of a catalytic amount of p‐toluenesulfonic acid (TsOH) in EtOH, in good to excellent yields (Scheme 1).     

A Convenient Synthesis of 1‐Alkoxy‐2‐alkyl‐1,2‐dihydroisoquinoline‐3,4‐diones Utilizing the Reaction of 2‐(Dialkoxymethyl)phenyllithiums with Dimethyl Oxalate

A new and convenient method for the preparation of 1,2‐dihydroisoquinoline‐3,4‐diones with alkoxy and alkyl groups at the 4‐ and 3‐positions, respectively, using an easily operated three‐step sequence starting from 2‐(dialkoxymethyl)phenyl bromides has been developed. Thus, the starting materials are treated with BuLi to generate 2‐(dialkoxymethyl)phenyllithiums, which are allowed to react with (COOMe)₂ to give methyl 2‐(dialkoxymethyl)phenyl‐2‐oxoacetates. These are then transformed into the corresponding secondary amides by the reaction with primary amines. Treatment of these keto amides with a catalytic amount of TsOH?H₂O affords the desired products. In order to demonstrate the synthetic utility of these products, transformation of one of them into the corresponding isoquinoline‐1,3,4(2H)‐trione derivative by the oxidation with PCC was achieved.     

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.     

Synthesis of Dialkyl 2‐(Alkylamino)‐4,9‐dihydro‐9‐oxocyclohepta[b]pyran‐3,4‐dicarboxylates

Dialkyl 2‐(alkylamino)‐4,9‐dihydro‐9‐oxocyclohepta[b]pyran‐3,4‐dicarboxylates are prepared in a one‐pot three‐component reaction of alkyl isocyanide, dialkyl acetylenedicarboxylate, and α‐tropolone (=2‐hydroxycyclohepta‐2,4,6‐trienone). The reaction proceeds smoothly at room temperature and under neutral conditions to afford tropolone derivatives in high 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.     

Ring‐opening polymerization of 1,4‐dioxan‐2‐one initiated by lanthanum isopropoxide in bulk

Lanthanum isopropoxide (La(OiPr)₃) has been synthesized and employed for ring‐opening polymerization of 1,4‐dioxan‐2‐one in bulk as a single‐component initiator. The influences of reaction conditions such as initiator concentration, reaction time, and reaction temperature on the polymerization were investigated. The kinetics indicated that the polymerization is first‐order with respect to the monomer concentration. The Mechanistic investigations according to ¹H NMR spectrum analysis demonstrated that the polymerization of PDO proceeded through a coordination‐insertion mechanism with a rupture of the acyl‐oxygen bond of the monomer rather than the alkyl‐oxygen bond cleavage. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5214–5222, 2008     

One‐Pot Syntheses of 2‐(2‐Sulfanyl‐4H‐3,1‐benzothiazin‐4‐yl)acetic Acid Derivatives via Reactions of 3‐(2‐Isothiocyanatophenyl)prop‐2‐enoic Acid Derivatives with Thiols or Sodium Sulfide

Two efficient methods for the preparation of 2‐(2‐sulfanyl‐4H‐3,1‐benzothiazin‐4‐yl)acetic acid derivatives 3 under mild conditions have been developed. The first method is based on the reaction of 3‐(2‐isothiocyanatophenyl)prop‐2‐enoates 1a – 1c with thiols in the presence of Et₃N in THF at room temperature, leading to the corresponding dithiocarbamate intermediates 2 , which underwent spontaneous cyclization at the same temperature by an attack of the S‐atom at the prop‐2‐enoyl moiety in a 1,4‐addition manner (Michael addition) to give 2‐(2‐sulfanyl‐4H‐3,1‐benzothiazin‐4‐yl)acetates in one pot. The second method involves treatment of 3‐(2‐isothiocyanatophenyl)prop‐2‐enoic acid derivatives 1b – 1d with Na₂S leading to the formation of 2‐(2‐sodiosulfanyl‐4H‐3,1‐benzothiazin‐4‐yl)acetic acid intermediates 5 by a similar addition/cyclization sequence, which are then allowed to react with alkyl or aryl halides to afford derivatives 3 . 2‐(2‐Thioxo‐4H‐3,1‐benzothiazin‐4‐yl)acetic acid derivatives 6 can be obtained by omitting the addition of halides.     

One‐Pot Four‐Component Synthesis of N2‐Alkyl‐N3‐[2‐(1,3,4‐oxadiazol‐2‐yl)aryl]benzofuran‐2,3‐diamines

A simple synthesis of N²‐alkyl‐N³‐[2‐(1,3,4‐oxadiazol‐2‐yl)aryl]benzofuran‐2,3‐diamines 5 via a one‐pot four‐component reaction is described (Scheme 1). A mixture of N‐(isocyanoimino)triphenylphosphorane ( 1 ), a 2‐aminobenzoic acid 2 , a 2‐hydroxybenzaldehyde 3 , and an isocyanide 4 in absolute EtOH at room temperature undergoes a smooth reaction to afford 5 in excellent yields (Table).     

One‐Pot Synthesis of Tetraalkyl Benzene‐1,2,3,5‐tetracarboxylates from a Four‐Component Reaction of Alkyl Propiolates and Alkyl 2‐Nitroethanoates Promoted by Ph3P

Alkyl 2‐nitroethanoates react with alkyl propiolates in the presence of triphenylphosphine (Ph₃P) in a mechanistically unprecedented reaction to afford tetraalkyl benzene‐1,2,3,5‐tetracarboxylates in moderate yields (36–42%).