Highly diastereoselective[3+2] cycloadditions between nonracemic p-tolysulfinimines and iminoesters: an efficient entry to enantiopure imidazolidines and vicinal diaminoalcohols

A new procedure for the asymmetric synthesis of imidazolidines and vicinal diamines is reported. The 1,3-dipolar cycloaddition between nonracemic p-tolylsulfinimines and azomethine ylides generated in situ from alpha-iminoesters and LDA produces N-sulfinylimidazolidines with a high degree of stereocontrol. In contrast, the presence of Lewis acids promotes formation of the cycloadducts through a highly diastereoselective process with opposite stereochemistry. Subsequent transformations of the imidazolidines including oxidative, reductive, and hydrolytic processes that provide easy access to vicinal diaminoalcohols have been explored. Among these, reductive cleavage of the aminal with LiAlH4 is an extremely efficient and general reaction for the synthesis of enantiopure N-sulfinyl-N'-benzyldiaminoalcohols     

Fine-tuned aminal cleavage: a concise route to differentially protected enantiopure syn-alpha,beta-diamino Esters

A survey of routes for aminal cleavage of N-sulfinylimidazolidines has been carried out, and selective conditions to cleave the aminal moiety while preserving the sulfinamide group unaltered have been found. Thus, the treatment of enantiopure N-sulfinylimidazolidines with aqueous H(3)PO(4) in THF affords enantiopure N-sulfinyldiamino esters in excellent yields, while the presence of MeOH as cosolvent allows for the simultaneous removal of the sulfinamide group and aminal cleavage. The behavior of these substrates in a variety of chemical transformations has been explored.     

The Synthesis of Some Pyrazolyl- and Thiazolylthienopyridines

2-acetyl-3-amino-4,6-dimethylthieno[2,3-b]pyridine 1 reacted with dimethoxy-tetrahydrofuran in acetic acid and ethyl cyanoacetate in the presence of ammonium acetate or with NaNO₂ in the presence of an AcOH/HCl mixture to produce 2–4. Compound 2 reacted with aromatic aldehydes, semicarbazide hydrochloride, thiosemicarbazide, and phenyl hydrazine or with hydrazine hydrate to give compounds 5a–c and 11a–d, respectively.

Chalcone 5 reacted with hydrazines, hydroxylamine hydrochloride, or thiourea to produce compounds 6–9. Thiosemicarbazone 11b reacted with α -haloester to produce the corresponding thiazolidinone derivatives 12a, b ; also it reacted with ω -bromoacetophenone to give thiazoline derivatives 13a, b .     

Chemoselective Reduction of Some Condensates derived from Chromone-3-carbaldehyde using Sm and Zn

Condensates 4–6 undergo reductive dimerization with Sm in THF containing aqueous NH₄Cl to produce 7–9, whereas with Zn under similar reaction condition 3–5 produce 10–12.     

Synthesis of Pyridothienopyridines and Arylazothienopyridines

Treatment of aminothienopyridine 3 with arylidenemalononitrile afford pyridothienopyridine 4. Also condensation of 3 with ethyl ethoxymethylene-cyanoacetae afford compound 5, which was cyclized in diphenyl ether into pyridothienopyridine 6. Thiourea derivative 7 was cyclized using Br₂/AcOH, and ethyl chloroacetate to afford thiazolothienopyridine 8 and thiazolidinylthienopyridine 9 respectively. Compound 15 was condensed with aromatic aldehydes to give the corresponding arylidenethienopyridines 16a–d. The latter compounds were underwent Michael addition with malononitrile to produce pyranothienopyridines 17a–d. Compound 15 was coupled with aromatic diazonium chloride to give the corresponding 2-arylazothienopyridine derivatives 20, but when treated with nitrous acis it dimerised into compound 19.     

Investigations of the Reaction of Pentacovalent Oxaphosphlenes with Isocyanates. Synthetic and Mechanistic Aspects

The reaction of the pentacovalent oxaphospholene 1 with isocyanates to produce the heterocycle 2 was followed by NMR in order to delineate the mechanism. The addition of 1 and 2 eq. of an isocyanate to 1 indicated very fast formation of 2 long-lived species that slowly rearranged to product. Cross-over experiments using 2 different isocyanates indicated the very fast formation of a statistical mixture of all 4 products 4–7. Kinetic analysis of the data was performed.     

Synthesis and Reactivity of 2-(1,2,3-Dithiazol-5- Ylidene)Aminothiophenes

The reaction of aminothiophenes (1) with Appel's salt (2) affords 2-(1,2,3-dithiazol-5-ylidene)aminothiophenes (3). Under the action of ZnCl₂, the latter compounds are transformed into 1,3-oxazin-4-one systems (4). The reactions of compounds 4 with dienophiles under atmospheric or high pressure give thienopyridines (6–11); the reactions with amines produce pyrimidinones (12) and guanidines (14–15).     

Synthesis of new annulated pyridazine derivatives and studying their antioxidant and antimicrobial activities

Benzil was reacted with cyanoacetohydrazide under microwave irradiation to give 3-oxo-5,6-diphenyl-2,3-dihydropyridazine-4-carbonitrile 1 which used as starting material for the synthesis of new heterocyclic compounds. Chlorination of pyridazinone 1 with POCl₃ afforded the chloro-pyridazine derivative 3, which then condensed with 2-aminothiazole or hydrazine hydrate to produce 3,4-diphenyl-5H-thiazolo[3′,2′:1,2]pyrimido[4,5-c]pyridazin-5-one 5 or 3-hydrazinyl-5,6-diphenylpyridazine-4-carbonitrile 6, respectively. New Schiff bases were obtained by condensation reactions of compound 6 with different aldehydes. On the other hand, compound 6 reacted with different carbon electrophiles naming acetyl acetone, diethyl malonate, and phenyl isothiocyanate producing new pyarazolo-pyridazine derivatives 11, 12, and 14, respectively. Chemical structures of all newly synthesized compounds were confirmed on the basis of spectral data and had been screened for antimicrobial and antioxidant activity.     

Studies on Organophosphorus Compounds XI: The Reaction of Phosphorus Reagents With Hydrazonoyl Halides,Hydrazonoyl Azides,and Shiff's Bases

N-(chloro-furan-2-yl)methylene-N′-(4-nitrophenyl)hydrazone (I) reacted with triethylphosphite to produce the phosphonate derivative III. The tetrazine derivative VI was produced by the interaction of I with diethyl-phosphite. Hydrazonoyl azide derivatives VIIIa–c reacted with triphenyl phosphine to form the iminophosphorane derivatives Xa–c. On the other hand, the azide derivative VIIIc reacted with the phosphonium ylide XI to form the 1,2,3-triazole adduct XIII. The reaction of triethyl phosphite with Shiff's bases XIVa–c yielded the corresponding phosphonates XVa–c. The structures of the newly prepared compounds were confirmed with the analytical and spectroscopic evidences.     

A Practical and Environmentally Friendly Preparation of 3-Carboxycoumarins

Abstract

The condensation of salicylaldehydes with Meldrum's acid in water at 75°C to produce 3-carboxycoumarin derivatives is described.     

Mercuric Acetate in Organic Synthesis: A Simple Procedure for the Synthesis of Pyrazolines1

Reaction of aldehyde hydrazones (1) with mercuric acetate leads to the formation of nitrile imines (2) which can react insitu with olefins to produce 1,3,5-trisubstituted 2-pyrazolines (4) in good yield.     

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS VI1–5: Utility of Lawesson's Reagent for Synthesis of Thiaphosphorine,Thioxanthene, and Thiaphosphole Derivatives

Arylidene malonate derivatives 2a–c reacted with Lawesson's reagent (1) LR in equimolar ratio to yield the oxathiaphosphorine derivatives 3a–c. The behaviour of LR towards cyclic ketones was also examined and yielded the thioxanthene derivatives 5a,b. On the other hand, arylidene pyrazolone 8 reacted with LR to give the phosphole 10. Aminobenzenethiophene 11 reacted with LR under reflux to produce the corresponding thiazaphosphorine 12.     

ONE-POT OXIDATION OF AZOMETHINE COMPOUNDS INTO ARENECARBOXYLIC ACIDS

Aromatic azomethine compounds, such as aldazines 1, aldoximes 7 and tosylhydrazones 8 oxidized with 30% hydrogen peroxide in the presence of poly(bis-1,2-phenylene) diselenide (6) as catalyst produce arenecarboxylic acids 2 mostly in high to excellent yields. The presented one-pot procedure has a synthetic value.     

Synthesis and Reactions of Polynuclear Heterocycles: Azolothienopyrimidines and Thienothiazolopyrimidines

We prepared a thieno[2,3-d]pyrimidine compound fused with a thiazolo ring to produce biologicaly active compounds. In a one-step reaction, 2-arylmethylene derivative (3) was prepared via the reaction of a ternary mixture of 2-thioxo-1,2,3,4-tetrahydrocyclohepteno[4,5]thieno[2,3-d]pyrimi-dine-4-one (2), cloroacetic acid, and a proper aldehyde. The reaction of 2 with 3-chloropent-2,4-dione in ethanolic potassium hydroxide yielded the S-acetylacetone derivative 4e. The latter compound reacted with hydrazine hydrate and phenyl hydrazine to give 2-pyrazolthio derivatives 8a,b, respectively. Compound 4e also underwent cyclization on boiling with acetic anhydride/pyridine solution to form 2-acetyl-3-methyl thiazolo[3,2-a]cyclohepteno[4,5]thieno[2,3-d] pyrimidine-5-one (9). To support the structure 9, it gave a characteristic reaction for the 2-acetyl group. The 2-methylthio derivatives 4a underwent further alkylation at N₃ to give 6a,b. The purpose of the synthesis of thienopyrimidine derivatives is due to high biological activities. The 4-oxo-thienopyrimidine derivatives acted as inhibitors of adenosine kinase, platelet aggregation, antilukemia, and anticancer activities.     

Studies on Organophosphorus Compounds VII1,2: Transformation of Steroidal Ketones with Lawesson's Reagent into Thioxo and Heterofused Steroids. Results of Antimicrobial and Antifungal Activity

The reactivity of Lawesson's reagent (LR) toward some steroidal hormones was studied, 4-androsten-3,17-dione 2 reacted with LR to produce the corresponding thioxosteroids 3 and 4. Epi-androsterone 5 showed a great activity to LR and produced 3β-mercaptospiro-(androstan-17,4′dithiaphosphetan)thione 8 and the sulfide derivative 9. Also progesterone 10 reacted with LR to yield the thiaphospholo[3′, 4′:16,17]androsten-3-one 13 and the sulfide product 16. The new modified steroidal derivatives thieno[2′,3′:2,3]cholestan 18 and thieno[2′,3′:2,3]-androstan 20 were synthesized and examined against LR, the corresponding thiazaphosphorinothieno steroidal derivatives 23 and 24 were isolated respectively. The in vitro biological activity of some newly synthesized compounds against bacteria, yeast, and fungi was studied.     

Efficient α-Thiocyanation of Ketones Using Pyridinium Hydrobromide Perbromide

Abstract

The direct α-thiocyanation of ketones with ammonium thiocyanate has been achieved using pyridinium hydrobromide perbromide under mild and neutral conditions to produce α-ketothiocyanates in excellent yields and with high selectivity.     

Green technologies in organic synthesis: self-condensation of enamines,enaminones and enaminoesters under microwave irradiation in ionic liquid

Abstract

Utilizing green technologies as microwave (MW) irradiation and ionic liquids (ILs), we could produce 1,3,5-trisubstituted benzene 3, 7, 9, and 14 by self-condensation of enamines 1, enaminones 4, 8, and enaminoester 10, respectively, in the presence of pyridinium chloride ([PyH]Cl) for short time. Also, we synthesized pyridine derivatives 17, upon irradiating enaminones 4 in domestic MW oven for short time.     

Saccharopolytide A,a new cyclic tetrapeptide with rare 4-hydroxy-proline moieties from the deep-sea derived actinomycete Saccharopolyspora cebuensis MCCC 1A09850

A genome mining analysis on the deep-sea derived actinomycete Saccharopolyspora cebuensis MCCC 1A09850 indicated its potential to produce polypeptides. Accordingly, a systematic chemical investigation was conducted, which resulted in the isolation of one new cyclic tetrapeptide (saccharopolytide A, 1) and two known polyketides (2, 3) along with six other miscellaneous compounds (4?9). Mainly by analysis of the 1D, 2D NMR and MS data, the chemical structure of saccharopolytide A was established as cyclo-(l-Leu-4-hydroxy-l-Pro-l-Phe-4-hydroxy-l-Pro). All isolates were evaluated for anti-allergic and anti-tumor bioactivities. Indol-3-carbaldehyde (4) showed weak anti-allergic effect with IC₅₀ value of 55.75 μg/mL. And 2 showed weak anti-proliferative activity against Hela and H1299 tumor cell lines. Our results consolidate the potential of deep-sea-derived microorganisms to produce structurally interesting compounds.     

On Regioselectivity of Aldol Condensation of Aromatic Aldehydes with Borate Complex of Acetylacetone

While cinnamoyl acetone 1 is obtained in good yield by a condensation of 3 molar excess of a borate complex of acetylacetone with benzaldehyde, products of Knoevenagel condensation 2 are predominantly obtained with furfural and 5-substituted furfurals. Cinnamoyl acetone 1 can be further condensed with furfural to form unsymmetrical curcuminoid 5. Compound 2a does not produce any new products under the same conditions. Compounds 3 and 5 are good inhibitors of growth of protozoan Trichomonas vaginalis.     

Kinetic Resolution of Piperazine-2-Carboxamide by Leucine Aminopeptidase. An Application in the Synthesis of the Nucleoside Transport Blocker (-) Draflazine

The resolution of N-t-Boc-piperazine carboxamide 5 proceeded smoothly in the presence of leucine aminopeptidase to produce acid (S)-1 and amide (R)-5 with good optical purity. Sequential alkylation and functional group manipulation of carboxamide (S)-5 provided the known nucleoside transport blocker draflazine (-) 2.