Lactim Ethers Research Articles

Direct access to vicinally functionalized and N-trifluoroacetylated (bicyclic)ketopiperazines using a readily affordable N-heterocyclic anhydride.

Functionalized 2-piperazinones play essential roles as conformationally-constrained peptidomimetics by mimicking inverse γ-turns in peptides. Here, we describe an efficient, scalable, stereoselective, modular, and chemoselective annulation protocol between a novel N-trifluoroacetyl anhydride and several reactive partners, including lactim ethers, imidoyl chlorides, aryl aldimines, and 1,3-azadienes, leading to vicinally functionalized (bicyclic) 2-piperazinones.

STUDY OF LACTAMS. VI. SYNTHESIS OF 6-SUBSTITUTED PURINO[8,9-1 1 ,2 2 ]ISOINDOLINES

It is shown with 1-ethoxyisoindolenine that the reaction of lactim ethers with α-amino-α-cyanoacetamide also extends to partly aromatized lactim ethers, although these react much less readily. Condensation of 1-ethoxyisoindolenine with α-amino-cyanoacetamide gives 4-carbamido-5-aminoimidazo[1, 2-1′, 2′]isoindoline, from which a new series of purinoisoindioline derivatives is synthesized. Authors: R. G. Glushkov, O. Yu. Magidson. English Translation in Chemistry of Heterocyclic Compounds , 1965, 1 (1), pp 57-59 http://link.springer.com/article/10.1007/BF01168921

Synthesis of 5-Amino-4-(2-azacycloalkylidene)-2-phenyl-2,4-dihydro-3H-pyrazol-3-ones

The reaction 5-amino-2-phenyl-3,4-dihydro-3H-pyrazol-3-one with activated lactams (lactim ethers, lactam acetals, and methylthioalkylidene iminium salts) was investigated. It occurs on the active methylene group of 5-amino-2-phenyl-3,4-dihydro-3H-pyrazol-3-one to furnish cyclic enamines, 5-amino-4-(2-azacycloalkylidene)-2-phenyl-2,4-dihydro-3H-pyrazol-3-ones and 5-amino-4-(1-methyl-2-azacycloalkylidene)-2-phenyl-2,4-dihydro-3H-pyrazol-3-ones.

Converting dipyrrinones to lactim ethers to fluorescent N,N′-difluoroboryl derivatives

A high-yield straightforward conversion of lactams to lactim ethers is shown by the conversion of (10H)-dipyrrin-1-ones to (11H)-dipyrrin-1-ol methyl and ethyl ethers in 90% yield from heating in neat trimethyl or triethyl phosphite at 160°C. Unlike the parent dipyrrinones, which form intermolecularly hydrogen-bonded dimers in CHCl3, their lactim ethers are shown to be monomeric by vapor pressure osmometry. The latter react with boron trifluoride etherate to N,N′-bridged BF2 derivatives that exhibit strong fluorescence (φF 0.6–0.8) near 535 nm. X-Ray crystal structures were obtained of the lactim ethyl ether of kryptopyrromethenone and the BF2 derivative of the lactim ethyl ether 2,3-diethyl-7,8-dimethyl-(10H)-dipyrrin-1-one.

New synthesis of pyrido[4,3-b]indoles (γ-carbolines) on the basis of indolin-2-one lactim ether

Condensation of indolin-2-one (oxindole) lactim ether with malononitrile leads to 2-dicyanomethylidene-2,3-dihydroindole, the reaction of which with dimethylformamide diethyl acetal (or with triethyl orthoformate) and the subsequent cyclization afford 4-cyanopyrido[4,3- b]indoles (γ-carbolines). 3-Amino-4-cyanopyrido[4,3-b]indole was used in the synthesis of substituted pyrimido[4,5-c]-γ-carbolines.

Microwave-Assisted, Solvent-Free Synthesis of Several Quinazoline Alkaloid Frameworks

Microwave irradiation leads to a considerable improvement of the cyclocondensation between anthranilic acid and lactim ethers derived from piperazine-2,5-diones in terms of reaction times, yields, and stereocenter integrity. This reaction has been used to prepare some derivatives of the pyrazino[2,1- B]quinazoline-3,6-dione system present in many quinazoline alkaloids. It could also be applied to the synthesis of compounds containing the complete hexacyclic ring system of the anti-MDR natural product N-acetyl-ardeemin, and other comprising the pentacyclic framework of circumdatin E. The microwave-assisted reaction was also much better than the thermal one when applied to a bis-lactim ether, leading to the corresponding pentacyclic pyrazino[2,1- B:5,4- B′]diquinazoline-8,16-dione in excellent yield.

Study of Reactions of Lactim Ethers with Cyanoacetohydrazide.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

New synthesis of benzo[b][1,6]naphthyridines and pyrido[4,3-b]benz[f]azepines from lactim ethers of 3,4-dihydrocarbostyril and 1H-2,3,4,5-tetrahydrobenz[b]azepin-2-one

Condensation of lactim ethers of 3,4-dihydrocarbostyril and 1H-2,3,4,5-tetrahydrobenz[b]azepin-2-one with malonodinitrile, cyanoacetamide, and ethyl cyanoacetate gave the corresponding 2-methylidene derivatives. Their reactions with dimethylformamide diethyl acetal followed by cyclization into benzo[b][1,6]naphthyridines and pyrido[4,3-b]benz[f ]azepines were studied.

Study of reactions of lactim ethers with cyanoacetohydrazide

Main pathways in reactions of lactim ethers with cyanoacetic acid hydrazide depend on the ring size of the starting lactim ether. Five-membered O-methylbutyrolactim produces pre-dominantly 3-amino-4-(pyrrolidin-2-ylidene)-4,5-dihydropyrazol-5-one, whereas condensation of six-and seven-membered lactim ethers (O-methylvalero-and O-methylcaprolactim, respectively) affords the corresponding polymethylenetriazoles as the major products.

Diastereoselective Alkylation of a Proline-Derived Bicyclic Lactim Ether

N-Boc-protected L-proline (6) was converted into the bicyclic lactim ether (8aS)-6,7,8,8a-tetrahydro-1-methoxypyrrolo[1,2-a]pyrazin-4(3H)-one (5) in four steps (Scheme 1). Deprotonation with LDA or LHMDS and subsequent alkylation resulted in the diastereoisomeric products cis- and trans-9. The diastereoselectivity was mainly dependent on the electrophile. Whereas small alkyl halides gave preferably cis-9, sterically more-demanding alkyl halides resulted in cis/trans mixtures. Electrophiles bearing a π-system favored the trans-products 9. Some isolated cis- and trans-lactim ethers 9 were converted to the corresponding diketopiperazines cis- and trans-10 by acid hydrolysis. The structures and configurations of several compounds were confirmed by NMR and NOE experiments, as well as by X-ray crystallography (Figs. 1–4).

Five‐, Six‐, and Seven‐Membered Lactim Ethers. Methods of Synthesis and Chemical Properties

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

New Derivatives of 3,4‐Polymethylene‐1,2,4‐benzothiadiazine S,S‐Dioxides.

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A new stereocontrolled approach to fused polycyclic compounds containing a diketopiperazine ring

Representative (1 S)- and (4 S)-alkyl-1,4-dihydropyrazino[2,1- b]quinazoline-3,6-dione lactim ethers were regio- and diastereoselectively alkylated after metallation to give the corresponding 1,4- trans-isomers with retention of the stereocentres. The results were compared with the previously studied lactams. The (1 R,4 S)-dialkyl derivatives obtained by C(1)-alkyation with bifunctional reagents were lately cyclized to complex polycyclic compounds through a second N(2)-alkylation promoted by sodium iodide.

Five-, Six-, and Seven-membered Lactim Ethers. Methods of Synthesis and Chemical Properties. (Review)

Data on methods for the production of 5–7-membered lactim ethers and their chemical transformations published after 1970 are reviewed.

New Derivatives of 3,4-Polymethylene-1,2,4-benzothiadiazine S,S-Dioxides

A new method is proposed for obtaining 3,4-polymethylene-1,2,4-benzothiadiazine 1,1-dioxides by reacting o-halobenzenesulfonamides with lactim ethers. Attempts were undertaken to synthesize quaternary salts of the heterocycles obtained.

Solvent‐Free Cyclocondensation of Lactim Ethers with Anthranilic Acid under Microwave Irradiation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Solvent-Free Cyclocondensation of Lactim Ethers with Anthranilic Acid under Microwave Irradiation

Microwave irradiation greatly improves the results of the cyclocondensation between anthranilic acid and lactim ethers derived from 2,5-piperazinediones in terms of reaction times, yields and stereocenter integrity, leading to pyrazino[2,1-b]quinazoline-3,6-diones. The microwave-assisted reaction was also much better than the thermal one when applied to a bis-lactim ether, leading to the corresponding pentacyclic pyrazino [2,1-b:5,4-b']diquinazoline-5,13-dione in excellent yield, and it also improved the preparation of compounds containing the ring system of the anti-MDR natural product N-acetylardeemin.

Synthesis and Study of Lactim Ethers of 3,4‐Dihydrocarbostyryl and 2,3,4,5‐Tetrahydrobenz[b]azepin‐2‐one.

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Synthesis and Structure of a Monomeric Chiral Lithium Dialkylaluminium Amide Derived from Schöllkopf’s Bis‐lactim Ether and α‐(Methylbenzyl)benzylamine

AbstractCrystals of a monomeric lithium dialkylaluminium amide containing two different chiral amide moieties have been isolated from the reaction of lithiated Schöllkopf’s bis‐lactim ether complexed by pmdta with the diethylaluminium amide of (S)‐α‐(methylbenzyl)benzylamine, with single crystal X‐ray diffraction revealing a migration of the Li cation in the aluminate from its initial position on the pyrazine ring of the lactim ether precursor. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Lactim Ethers in the Synthesis of 1,2‐Polymethylene‐4‐quinazolones.

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