New Approach to 4‐ and 5‐Aminopyrazole Derivatives

3‐Oxo‐3‐(pyrrol‐2‐yl)‐propanenitrile 1 coupled with aromatic diazonium salts to yield the corresponding 2‐arylhydrazones 2a–c. The latter products reacted with chloroacetonitrile and ethyl chloroacetate to yield 4‐aminopyrazole derivatives 5a–f. Reaction of 2 with hydrazine hydrate led to formation of 5‐amino‐4‐arylazopyrazole 6a–c. Compound 1 reacted also with trichloroacetonitrile to yield enamine 7, which in turn reacted with hydrazine hydrate to yield 5‐amino‐3‐(pyrrol‐2‐yl)‐pyrazole‐4‐carbonitrile 8.     

New bis‐Pyrazole Derivatives Synthesized From Aryl‐ and Xylyl‐Linked bis(β‐Diketone) Precursors

The synthesis and characterization of six new aryl‐linked, and in one instance xylyl‐linked, bis‐pyrazoles are reported. The X‐ray structures of two of these derivatives are also presented.     

Facile Entry to 4‐ and 5‐Hydroxybenzofuran and to Their Amino Derivatives

An innovative one‐step procedure for the synthesis of 4‐hydroxybenzofuran and an improved synthesis of 5‐hydroxybenzofuran is reported. Such compounds were also transformed into their amino derivatives via Smiles rearrangement with good to high overall yields.     

Antibacterial Activities of New (E) 2‐Cyano‐3‐(3′,4′‐dimethoxyphenyl)‐2‐propenoylamide Derivatives

(E) 2‐Cyano‐3‐(3′,4′‐dimethoxyphenyl)‐2‐propenoyl chloride (2) underwent mono‐ and binucleophilic displacement with hydrazines, amines, ureas, and aromatic bifunction amines to give new 2‐propenoyl hydrazines (4 and 5), 2‐propenoylamide (6, 7, 12, 13, 15, 17, 19, 21), and 2‐thiol propenoate (22–24). Some of these products were cyclized to give novel heterocyclic derivatives (8, 10, 14, 16, and 20).     

Enantioselective Synthesis of (R)‐2‐Methylalkanoic Acids: A Convenient Approach to α‐Substituted Chiral Carboxylic Acid Derivatives

Abstract

Racemization‐free deacylation of N‐acylimidazolidine‐2‐ones using lithium hydroperoxide affords the corresponding α‐substituted chiral carboxylic acids in high yield while permitting recovery of the chiral auxiliary.     

Synthesis of 3‐Aryl‐2‐benzoylbenzofuran Derivatives using Manganese(III) Acetate–Mediated Addition of Dimedon to Chalcone Derivatives

3‐Aryl‐2‐benzoylbenzofurans were synthesized by the reaction of α‐carboradical produced from dimedon by oxidizing with manganese(III) acetate in acetic acid and the chalcone derivatives.     

The Chemistry of 2‐Alkenyl‐5(4H)‐ oxazolones. IX. Acid‐Catalyzed Oligomerization

Abstract

Results of the acid catalyzed oligomerization of 2‐alkenyl‐5(4H)‐oxazolones are reported. Employing LC–MS and preparative LC methods, the oligomeric mixtures were characterized by NMR analyses and were discovered to consist of exclusively cyclic trimers to decamers, with tetramers and pentamers predominating. A nucleophilic oligomerization mechanism involving Michael addition and C‐alkylation of a ketene‐aminal to protonated monomer was proposed that resulted in irreversible cyclization at the trimer propagation stage. Subsequent oligomerization proceeded via enolization of α‐hydrogens on 2‐substituted 5(4H)‐oxazolone products and continued Michael addition to protonated monomer. In the sense that when both enolizable hydrogens and protonated monomer are present, the oligomerization can be regarded as being “living.”     

A Diels-Alder Approach to 4,4′-Ihiobis-(Phihalic Acid) Derivatives

Reactions of 3,3′-thiobis(2,5-dihydrothiophene 1,1 dioxide) (2) with several dienophiles afforded Diels Alder adducts 4–7. Compound 7 was aromatized to give 4,4′-thio-bis(dimethyl phthalate) (9), a potential intermediate to sulfur- bridged polyimides.     

Facile Way to Synthesize Nα‐Boc‐Nβ‐Cbz‐2,3‐ Diaminopropionic Acid Derivatives via 5‐Oxazolidinone

An economical and facile synthesis of N^α‐Boc‐N^β‐Cbz‐2,3‐diaminopropionic acid derivatives is reported. The key aspect of this method is employment of N‐Boc‐5‐oxazolidinone moiety to simultaneously provide proper protection of α‐amido and α‐carboxyl functional groups and affords the desired isocyanate 5 successfully by a Curtius rearrangement. The obtained intermediate 6 can be readily converted to various derivatives of N^α‐Boc‐N^β‐Cbz‐2,3‐diaminopropionic acid by conventional procedure.     

Organic Base‐Catalyzed Stereoselective Isomerizations of 4‐Hydroxy‐4‐phenyl‐but‐2‐ynoic Acid Methyl Ester to (E)‐ and (Z)‐4‐Oxo‐4‐phenyl‐but‐2‐enoic Acid Methyl Esters

We have developed a 1,4‐diazabicyclo[2.2.2]octane (DABCO)‐catalyzed isomerization of 4‐hydroxy‐4‐phenyl‐but‐2‐ynoic acid methyl ester to (E)‐4‐oxo‐4‐phenyl‐but‐2‐enoic acid methyl ester and an N,N‐diisopropylethylamine‐catalyzed isomerization of the same substrate to (Z)‐4‐oxo‐4‐phenyl‐but‐2‐enoic acid methyl ester.     

Synthesis of (E)‐ and (Z)‐5‐(Bromomethylene)furan‐2(5H)‐one by Bromodecarboxylation of (E)‐2‐(5‐Oxofuran‐2(5H)‐ylidene)acetic Acid

(E)‐ and (Z)‐5‐(bromomethylene)furan‐2(5H)‐one have been prepared starting from the commercially available adduct between furan and maleic anhydride. A bromodecarboxylation reaction is a key step in the synthesis. The reaction gives the (E)‐ or (Z)‐5‐(bromomethylene)furan‐2(5H)‐one as the major product, dependent on the method used in the bromodecarboxylation.     

General and Facial Synthesis of 2‐Amino‐5‐halogenpyrimidine‐4‐carboxylic Acids and Their Derivatives

A facile synthetic approach to 2‐amino‐5‐halogen‐pyrimidine‐4‐carboxylic acids from 5‐halogen‐2‐methylsulfonylpyrimidine‐4‐carboxylic acid by nucleophilic displacement of the methylsulfonyl group with primary and secondary aliphatic amines has been developed. The titled amino acids underwent decarboxylation, yielding 2‐amino‐5‐halogenpyrimidines. Starting from 2‐amino‐5‐chloropyrimidine‐4‐carboxylic acid chlorides, 2‐[5‐chloro‐2‐(amino)‐4‐pyrimidinyl]‐2‐oxo‐1‐(2‐pyridyl)‐ethyl cyanides were obtained in excellent yields.     

Synthesis of 3‐Aryl‐5‐t‐butylsalicylaldehydes and their Chiral Schiff Base Compounds

Six meta‐substituted salicylaldehyde compounds have been prepared in 68–90% yields by the Suzuki–Miyaura coupling reaction using 3‐bromo‐5‐t‐butylsalicylaldehyde (1a) and arylboronic acids (2a–f) as reactants. Among the obtained products, 3‐(4‐fluorophenyl)‐5‐t‐butylsalicylaldehyde (3b), 3‐(4‐methylphenyl)‐5‐t‐butylsalicylaldehyde (3d), 3‐(1‐naphthyl)‐5‐t‐butylsalicylaldehyde (3e), and 3‐(2‐naphthyl)‐5‐t‐butylsalicylaldehyde (3f) have not been reported so far. A series of new Schiff base ligands (L1–L10) were obtained in 51–89% yields from these salicylaldehyde derivatives.     

Convenient Method for the Preparation of 2‐Aryl‐1H‐benzimidazole‐4‐carboxylic Acids

The oxidative cyclization of 2,3‐diaminobenzoic acid and aromatic aldehydes to give 2‐aryl‐1H‐benzimidazole‐4‐carboxylic acids is reported. Moreover, three methods were compared in different perspectives from experimental manipulation to yield.     

Novel Synthetic Route of (2S)‐6‐Fluoro‐4‐oxo‐3,4‐dihydro‐2H‐chromene‐2‐carboxylic Acid

(2S)‐6‐Fluoro‐4‐oxo‐3,4‐dihydro‐2H‐chromene‐2‐carboxylic acid, a key intermediate of Fidarestat, was synthesized from natural chiral pool D‐mannitol. Its structure was confirmed by optical analyses, elemental analyses, and IR, ¹H NMR, and ESI‐MS spectra.     

New and Concise Approach to (R)-α-Lipoic Acid

A concise enantiospecific synthesis of (S)-6,8-bis(methylsulfonyloxy)-octanoic acid (2), a ready precursor of (R)-(+)-α-lipoic acid (1), is reported. The key step of the synthesis is the coupling of the tosylate derived from (R)-malic acid with phenylpropyl magnesium bromide. A recently reported green procedure was used for the oxidative unmasking of the phenyl group, used as a latent carboxyl group.     

Novel Synthesis of 5‐Substituted‐3‐phenylindole‐2‐(1,2,4‐triazole) Derivatives

Various substituted 3‐phenylindole 2‐carboxylates (1a–c) were prepared according to the literature methods. These carboxylates (1a–c) on reaction with thiosemicarbazide yielded 5‐substituted‐3‐phenylindol‐2‐(1,2,4‐triazole‐3‐thione) (2a–c) on refluxing in pyridine for 8 h. The 5‐substituted‐3‐phenylindole‐2‐[1,2,4‐triazolo‐3‐thioacetic acid] (3a–c) were prepared from 5‐substituted‐3‐phenyl indole‐2‐[1,2,4‐triazole‐3‐thione] (2a–c) on reaction with an appropriate alkylating agent and sodium acetate in acetic acid. Further, (3a–c) were reacted with acetic anhydride to bring about a cyclocondensation reaction to yield 5‐substituted‐3‐phenylindol‐2‐thiazolo(2,3‐b)‐triazole (4a–c). The 5‐substituted‐3‐phenylindole‐2‐[1,2,4‐triazolo‐3‐acetic acid] (3a–c) were reacted with o‐phenylenediamino dihydrochloride in ethylene glycol to yield 5‐substituted‐3‐phenylindole‐1,2,4‐triazolo‐3′‐yl‐thiomethyl)benzimidazoles (5a–c).     

Convenient Preparation of 2,7,8‐Trimethyl‐6‐hydroxychroman‐2‐carboxylic Acid (γ‐Trolox)

The title chroman is useful in synthesis and as a water‐soluble analog of γ‐tocopherol, a member of the vitamin E family. This new synthesis of γ‐trolox proceeds via selective aromatic demethylation of Trolox, the more easily available 2,5,7,8‐tetramethyl homolog compound. This route is shorter than the previous synthesis, avoids the use of cyanide and methoxybutadiene, and requires no chromatography.     

Thallium(III) Nitrate Mediated Ring Contraction of 2‐Aryl‐1,2,3,4‐tetrahydro‐4‐quinolones: Stereoselective Synthesis of trans Methyl 2‐Aryl‐2,3‐dihydroindol‐3‐carboxylates

The ring contraction of N‐acetyl‐2‐aryl‐1,2,3,4‐tetrahydro‐4‐quinolones 1a–d with thallium(III) nitrate in trimethyl orthoformate afforded stereoselectively trans methyl N‐acetyl‐2‐aryl‐2,3‐dihydroindol‐3‐carboxylates 5a–d by oxidative rearrangement of aryl ring A.     

Bromination of 5‐Methoxyindane: Synthesis of New Benzoindenone Derivatives and Ready Access to 7H‐Benzo[c]fluoren‐7‐one Skeleton

The photobromination of 5‐methoxyindane and 5‐methoxyindanone was studied at both high and low temperatures. 1,2,3‐Tribromo‐6‐methoxyindene was easily synthesized by photolytic bromination of 5‐methoxyindane at low temperature. 1,1,2,3‐Tetrabromo‐6‐methoxyindene was obtained from the photobromination of 5‐methoxyindan at 77 °C, which could then be easily converted to the 2,3‐dibromo‐6‐methoxyindene by silver‐supported hydrolysis. Photochemical bromination of 5‐methoxy‐1‐indanone with N‐bromosuccinimide (NBS) gave 3‐bromo‐6‐methoxyindene, which upon thermolysis gave a benzo[c]fluorenone derivative.