Azetidine Derivatives Research Articles

Experimental and computational studies of the structure and vibrational spectra of azetidine derivatives

The IR spectra of 3,3-dinitroazetidine (DNAZ), 1-nitroso-3,3-dinitroazetidine (nitroso-DNAZ), and azetidine in solid argon matrices were measured. In addition, the structures and harmonic vibrational frequencies of these molecules were theoretically evaluated using three electronic structure methods: restricted Hartree–Fock and the B3LYP and BP86 density functional methods. The computed geometries are compared with the experimental measurements. The computed vibrational frequencies are used to determine the types of molecular motion associated with each of the observed experimental bands. Comparison with the experimental spectra provides important information about the ability of these computational methods to describe the vibrational modes in these highly polar strained ring compounds.

Chiral C2-symmetric 2,4-disubstituted azetidines as chiral ligands in the addition of diethylzinc to aldehydes

Chiral C 2-symmetric 2,4-disubstituted azetidine derivatives having a β-amino alcohol moiety have been successfully synthesized and their stereoselective catalytic abilities have been examined in the asymmetric addition of diethylzinc to aldehydes in hexane. When N-(2,2-diphenyl-2-hydroxyethyl)-( S, S)-2,4-bis(methoxymethyl)azetidine 12 was used as a catalytic chiral ligand, the production of sec-alcohols having an S-absolute configuration could be achieved in high chemical yields (92–99%) and high enantiomeric excesses (83–93% for arylaldehydes and 63–65% for aliphatic aldehydes). For some arylaldehydes, the enantioselectivities are higher than the corresponding chiral C 2-symmetric 2,5-disubstituted pyrrolidine ligands. However, when the chiral C 2-symmetric azetidine derivatives 13 and 14, which have bulky substituents on the 2,4-positions were used as the chiral ligands under the same reaction conditions, the enantiomeric excesses of the corresponding sec-alcohols decreased to 20–30%.

Novel efficient synthesis of 1-azabicyclo[1.1.0]butane and its application to the synthesis of 1-(1,3-thiazolin-2-yl)azetidine-3-thiol useful for the pendant moiety of an oral 1β-methylcarbapenem antibiotic L-084

1-Azabicyclo[1.1.0]butane 2 was successfully synthesized by treatment of 2,3-dibromopropylamine hydrobromide 4 with organolithium compounds and was readily converted to 1-(1,3-thiazolin-2-yl)azetidine-3-thiol hydrochloride 1 and versatile azetidine derivatives 9 and 10.

Syntheses and Transformations of Azeto[2,1-a]- and -[2,1- b]isoquinolines and Azeto[1' ,2':1,2]pyrido[3,4-b]indoles

The syntheses, transformations and some of the biological features of azeto[2,1-a]­ and -[2,1-b]isoquinolines and azeto[1',2':1,2]pyrido[3,4-b]indoles are reviewed. Both angularly and linearly fused azetidine derivatives of isoquinolines are known. As concerns the related pyridoindoles, only the angularly fused azeto[1',2':1,2]pyrido[3,4-b]indoles have been prepared and investigated. The most interesting and characteristic transformations of azetoisoquinolines and azeto[1',2':1,2]pyrido[3,4-b]indoles are the ring enlargement reactions; these result, for example, in eight-membered ring derivatives which were difficult to synthesize by earlier methods. Such derivatives are versatile intermediates for the synthesis of biologically important compounds. Some of the azetoisoquinolin-2-ones synthesized and tested to date display weak antibiotic activity. Several other azetoisoquinolines exhibit a wide range of pharmacological activities.

3-Diazo-1-benzyloxycarbonylpyrrolidin-2-one

The title compound, C12H11N3O3, was an unexpected reaction product. It is a rare example of a cyclic diazo amide and is a potential precursor for important azetidine derivatives via Wolff rearrangement.

Photochemical Reactions of Tetrahydroquinoxalin‐2(1H)‐ones and Related Compound

AbstractPhotochemical behaviors of the pyrazinone derivatives 5,6,7,8‐tetrahydroquinoxalin‐2(1H)‐ones 1a–c and 1,5,6,7,8,9‐hexahydro‐2H‐cyclohepta[b]pyrazin‐2‐one 1d were investigated. Dye‐sensitized photo‐oxygenation of 1a‐c gave the 1:1 adducts 5a–c of the corresponding 3,8a‐epidioxy‐3,5,6,7,8,8a‐hexahydroquinoxalin‐2(1H)‐one 4 and H2O, whereas 1d gave 3,9a‐epidioxy‐1,3,5,6,7,8,9,9a‐octahydro‐2H‐cyclohepta[b]pyrazin‐2‐one 4d (Scheme 2). The different kind of products was interpreted as being the result of the ring strain and steric hindrance of endoperoxides produced from 1a–d with singlet oxygen. Irradiation of 1a–b in the presence of alkenes gave tricyclic azetidine derivatives 9 by [2 + 2] cycloaddition of the CN bond of 1 to the alkene.

Transformation of compounds containing C-N bonds on heterogeneous catalysts: Part V. Hydrogenolysis of C-N bonds in substituted azacycloalkanones: preparation of sterically hindered amines and amino derivatives

On various transition metal catalysts (Raney nickel, Pd/C, Pd black, RuO 2, Rh/C), the N-C(2) bond in N-benzoyl-2,2,4,4-tetraMe-azetidin-3-one ( 1) undergoes hydrogenolysis with 100% selectivity, as does that in the corresponding azetidine derivative 2 on Raney nickel; in the process, the oxo group in the ring in 1 is converted to a hydroxy group. In the analogues with higher numbers of ring atoms, only the latter hydrogenation proceeds; under identical reaction conditions, C-N hydrogenolysis does not occur. The rate of hydrogenolysis is increased by the carbonyl group at position 3 in azetidinone, as compared to that of azetidine, which does not possess the carbonyl function. A proposal is made concerning the reaction mechanism.

Cycloadditions in syntheses. XXXVII. Syntheses of 6-trifluoromethyl-1,2,4-triazines and -1,2,4-triazin-5-ones and their pericyclic reactions with olefins.

6-Trifluoromethyl-1, 2, 4-triazines and -1, 2, 4-triazin-5-ones were synthesized to investigate the role of the trifluoromethyl group in their thermal as well as photochemical cycloaddition reactions with olefins. In photochemical 2+2 cycloaddition using the triazin-5-ones and -3, 5-diones, the activation of the imine function by the trifluoromethyl group is demonstrated and a new route to azetidine derivatives having a trifluoromethyl group is disclosed. In thermal 4+2 cycloaddition using the corresponding triazines, acceleration of the so-called inverse electron demand Diels-Alder reaction is demonstrated. Clarification of the mechanisms of these reactions and their use in the synthesis of azetidin-2-ones and pyridines having a trifluoromethyl group are also described.

ChemInform Abstract: Iminophosphorane‐Mediated Syntheses of (1,2,4)Triazolo(5,1‐c) (1,2,4)triazines. The Unexpected Formation of Z,Z‐1,3‐Diazetidine‐2,4‐di‐imines. X‐Ray Molecular Structure of 7‐(p‐Chloroanilino)‐8‐(p‐chlorophenyl)‐3‐methyl(1,2,4)triazolo(5,1‐c) (1,2,4)triazin‐4(8H)‐one and of 1,3‐Bis‐(p‐chlorophenyl)‐2,4‐bis‐(6‐methyl‐3‐methylthio‐5‐oxo‐4,5‐dihydro‐1,2,4‐triazin‐4‐ylimino)‐1,3‐diazetidine.

AbstractThe phosphoranylideneaminotriazine (Ib) obtained from (Ia) reacts with aryl isocyanates (II) to give the unexpected azetidine derivatives (III) which are converted to the title compounds (IV) on treatment with aqueous Et‐OH.

ChemInform Abstract: THE PHOTOCYCLOADDITION OF 6‐SUBSTITUTED PHENANTHRIDINES TO ELECTRON‐RICH OLEFINS

AbstractDie Titelreaktion der Komponenten (I) und (II) in Ethanol wird untersucht.

The Photocycloaddition of 6-Substituted Phenanthridines to Electron-rich Olefins

Abstract The photocycloaddition reaction of 6-substituted phenanthridines and electron-rich olefins, such as trans-anethole and phenyl vinyl ether, is described. This reaction proceeds from the 1(π,π*) states of 6-substituted phenanthridines via the exciplex to give azocine and/or azetidine derivatives in ethanol.

ChemInform Abstract: PHOTOCYCLOADDITION OF 6‐CYANOPHENANTHRIDINE TO ELECTRON‐RICH OLEFINS

AbstractDie Photocycloaddition der elektronenreichen Olefine (II) an das Cyanphenanthridin (I) führt neben geringen Mengen Azetidin (III) hauptsächlich zu den ringerweiterten Produkten (IV), die Ethanol angelagert haben.

The Polymerization of Azetidines and Azetidine Derivatives

The cationic ring-opening polymerization of azetidine, N-alkylazetidines and a number of azetidines carrying a second functional group is reviewed. Some of these monomers lead to “living” polymers. The rate constants for the polymerization of different azetidines are discussed and compared with the rate constants for the polymerization of other four-membered heterocycles. The nucleophilic ring-opening polymerization of azetidinium salts is discussed. A new polymer with azetidinium endgroups is described. The synthesis, chemical properties, and applications of a number of polymers with pendant azetidinium substituents are described.

PHOTOCYCLOADDITION OF 6-CYANOPHENANTHRIDINE TO ELECTRON-RICH OLEFINS

Abstract Irradiations of 6-cyanophenanthridine in the presence of electron-rich olefins afforded the corresponding azocine and azetidine derivatives regiospecifically via their exciplex intermediates.

ChemInform Abstract: STRUCTURE AND BONDING IN CYCLIC PHOSPHORAMIDATES AS DETERMINED BY CARBON‐13 MAGNETIC RESONANCE

13C chemical shifts and 13C–31P couplings are reported for 11 cyclic phosphoramidates of ring sizes from four to nine. Vicinal couplings are compared with those of carbocyclic analogs and provide insight regarding the degree of nitrogen lone pair derealization into the N—P bond. For six-membered and larger rings, there appears to be nearly complete lone pair delocalization, i.e., a trigonal planar nitrogen atom. In azetidine derivatives the nitrogen lone pair remains localized, giving rise to a highly puckered ring conformation. Pyrrolidine derivatives are viewed as having a nitrogen with a partially delocalized electron pair.

Azetidine derivatives of tricyclic antidepressant agents

Tricyclic derivatives of azetidine were synthesized and screened for their potential antidepressant activity. The active series had the tricyclic ring attached to position 1 and a basic group in position 3 of the azetidine. The most interesting compounds were comparable to the reference standards for reserpine antagonism in mice, the most active being the dextrorotatory methylamino derivative 84. The pharmacological profile classifies it as a CNS stimulant devoid of peripheral anticholinergic activity.

Structure and bonding in cyclic phosphoramidates as determined by carbon-13 magnetic resonance

13C chemical shifts and 13C–31P couplings are reported for 11 cyclic phosphoramidates of ring sizes from four to nine. Vicinal couplings are compared with those of carbocyclic analogs and provide insight regarding the degree of nitrogen lone pair derealization into the N—P bond. For six-membered and larger rings, there appears to be nearly complete lone pair delocalization, i.e., a trigonal planar nitrogen atom. In azetidine derivatives the nitrogen lone pair remains localized, giving rise to a highly puckered ring conformation. Pyrrolidine derivatives are viewed as having a nitrogen with a partially delocalized electron pair.

Studies on Azetidine Derivatives. I. Synthesis of 3-Substituted Azetidine Derivatives

In order to find pharmacologically active azetidine derivatives, convenient procedures for the synthesis of 3-substituted azetidines have been investigated. 3-Azetidinyl mesylates (IV), prepared by treatment of azetidin-3-ols (I) with sulfenes, were shown to be useful intermediates for the synthesis of 3-substituted azetidines, 3-amino-, 3-cyano-, 3-guanidinoazetidines (V, VI and VIII) and azetidine-3-carboxylic acids (VII) via VI. 1-Cyclohexyl-3-guanidinoazetidine showed an excellent antihypertensive activity.

Studies on Azetidine Derivatives. II. Reactions and Stereochemistry of 3-Substituted 1-Cyclohexyl-2-phenylazetidines

The stereochemical course of diastereomeric 1-cyclohexyl-2-phenyl-3-azetidinyl mesylates (IVa and Va) was investigated with nucleophilic reagents. The retention of the configuration in these reactions and ring contracted products in some cases of reactions of IVa were observed. The presence of 1-azabicyclobutonium ions (VII and VIII) as intermediates in these reactions has been proposed from these results. The stereochemistry of 3-substituted azetidines obtained by nucleophilic reactions via IVa and Va was established by chemical evidence and nuclear magnetic resonance studies with a shift reagent, Eu (DPM)3.

Studies on Azetidine Derivatives. IV. Synthesis and Some Reactions of Azetidin-3-one Derivatives

Studies on Azetidine Derivatives. IV. Synthesis and Some Reactions of Azetidin-3-one Derivatives