A number of surveys of the chemistry of chiral aziridines have been published. Butler september 16, 2004 introduction aziridines 1 have been synthetic targets as well as useful building blocks in synthesis since gabriels 1888 discovery of the smallest nitrogen containing heterocycle. To the best of our knowledge this is the first case of aziridine formation with the intermediacy of l,3diaryl3hydroxyaminolpropanones and with oh as a leaving group in the ring closure. A fundamental improvement in the transitionmetalcatalyzed synthesis of aziridines has been reported recently by jenkins and cramer with their synthesis of a new octahedralironiicomplex3c. The reaction of ntosyl imines with in situ generated iodomethyllithium, with a simple and rapid experimental protocol, allows an efficient and general synthesis of aziridines. The solventfree and catalystfree conversion of an aziridine to an oxazolidinone using only carbon dioxide chau phung, a rani m. The synthesis and applications of nalkenyl aziridines nicholas a. Other examples show similar addition reactions to thiiranes and aziridines. Within heterocyclic chemistry, betalactams comprise an extraordinary class of strained compounds, recognized for their biological importance as potent antibiotics and their chemical value as flexible building blocks for the construction of diverse nitrogencontaining structures. Pieczonka, ewelina misztal, michal rachwalski, stanislaw lesniak. Mitomycin c, an aziridine, is used as a chemotherapeutic agent by virtue of its antitumour activity.
Synthesis of chiral 12aminoalkylaziridines via a self. Synthesis of aziridine 2phosphonates and their biological activities babiz, hakan m. However, if the aziridine ring is incorporated in a larger organic framework, such selectivity could be achieved, as it. Synthesis of new bicyclic aziridines containing chalcone analogs and investigation of their photochromic properties. Aziridines 1 undergo electrocyclic ring opening in a disrotatory manner upon irradiation and conrotatory ring opening upon thermolysis, giving azomethine ylides 2, which participate in 1,3dipolar cycloadditions scheme 1. Preparation of a versatile precursor of novel functionalized polymers.
The free internet journal for organic chemistry paper archive for organic chemistry arkivoc 2017, part ii, 223234 synthesis of chiral 12aminoalkylaziridines via a selfopening reaction of aziridine adam m. Opening of ntosyl aziridines 1 with water using catalyticamountofcana entry starting product time h. Among the synthetic routes available to access this interesting scaffold, the carbonylation of aziridines, in which. A mechanism to explain this novel reaction is proposed. There is an equilibrium between the dimer and the monomer, with the equilibrium lying heavily to the dimer. Most contemporary methods of chiral aziridine preparation have relied on the chiral pool. Nikolova application of aziridines for the synthesis of isoquinoline derivatives 106 the toxicity of aziridine derivatives will depend on its own structure and activity whilst sharing the general characteristics of the aziridine group.
Metal free onepot synthesis of 2substituted and 2,3disubstituted morpholines from aziridines hongnan sun, binbin huang, run lin, chao yang and wujiong xia. Aziridine is an organic compound consisting of the threemembered heterocycle ch22nh. Nunsubstituted aziridines can be opened with olefins in the presence of strong lewis acid bc 6 f 5 3. Besides their importance as reactive intermediates, many biologically active compounds also contain these threemembered rings. These aziridines undergo a ringopening reaction with a variety of carbon and heteronucleophiles, in good yield, and generally with good regioselectivity. Aziridines are organic compounds containing the aziridine functional group, a threemembered heterocycle with one amine nr and two methylene bridges cr 2. May 02, 20 general procedures for the synthesis of ndiphenylphosphinyl vinyl aziridines. Aziridine article about aziridine by the free dictionary.
Carbonylation of aziridines as a powerful tool for the. The solventfree and catalystfree conversion of an aziridine. Pharmaceutically active 2 and 2,3disubstituted morpholines. The tertiary amine dabco catalyzes the reaction of imines with phenacyl bromide derivatives to afford functionalized aziridines in high yields and stereoselectivities in a onepot process including the formation of ylides and their precursors. A reaction of a chiral aldimine derived from phenylalaninal proceeded with high diastereoselectivity. Nme aziridines via a rhodiumcatalyzed pathway free of external oxidants.
Chiral aziridines have found widespread use in organic synthesis. In addition, the reaction of 2,3disubstituted aziridines acyclic andor cyclic ones, separable mixtures of regioisomers 3l,m and 4l,m were obtained arising from isomeric ring opening table2, entries 12. Carbonylation of aziridines as a powerful tool for the synthesis of functionalized. Enantioselective and protecting groupfree synthesis of 1deoxythionojirimycin, 1deoxythiomannojirimycin, and 1deoxythiotalonojirimycin. Two types of azirine can be formed, the 1 hazirine and the 2hazirine.
They are typically used to react with the carboxylic acid groups on acrylic adhesives. Metalfree onepot synthesis of 2substituted and 2,3. The reaction of polyfunctional aziridine crosslinkers are acid catalyzed. Preparation and reactions of heterocyclic compounds i. Wulffs group has developed a robust catalytic asymmetric aziridination reaction providing. Nitrene addition to alkenes is a wellestablished method for the synthesis of. A strategy to functionalize polymers by ringopening reaction of aziridine hyeonjae jang,a jae tak lee,b and hyo jae yoon a adepartment of chemistry, korea university, seoul 6701, korea bdepartment of chemistry, sogang university, seoul, 121742, korea corresponding author, email.
Pages in category aziridines the following 15 pages are in this category, out of 15 total. Direct stereospecific synthesis of unprotected nhnme. The synthesis and applications of nalkenyl aziridines. In the wenker synthesis, the aminoethanol is converted to the sulfate ester, which. Jan 03, 2014 aziridines, the triangular, comparably highlystrained nitrogen analogues of epoxides, are important synthetic intermediates i. The resulting pale yellow solution was then stirred at 0 c for 30. Pdf aziridines are important precursors for the synthesis of various nitrogen containing bioactive.
This manuscript shows variety of methods for the synthesis and ring0opening of threemembered aziridines and their application for the synthesis of sixmembered isoquinolines. Metalfree onepot synthesis of optically pure morpholine derivatives from chiral aziridines. To crosslink, an active hydrogen must be available to open the aziridine ring. Investigation of methods for the synthesis of aziridines. Besides many recently published ruthenium, copper, and manganese catalysts, a novel macrocyclic tetracarbene ironii catalyst promotes the synthesis of aziridines in good yields and with low catalyst loadings. A visiblelight induced decarboxylative azadarzens reaction between naryl glycines and diazo compounds was developed, which affords various monosubstituted aziridines in good yields. Davisb aastrazeneca, mereside, alderley park, macclesfield, cheshire, sk10 4tg, uk bdepartment of chemistry, temple university, philadelphia, pa 19122. Formation of aziridines from chalcones and hydroxylamine. Various methods for the preparation of aziridines and azirines on the basis of ethyl. Aziridines ethylene imines are important building blocks in organic synthesis, because they allow for convenient access to amines, amino alcohols, diamines, and other useful nitrogencontaining molecules. Synthetic applications of nh aziridine containing compounds.
Goups of 56 male dowwistar rats were injected intraperitoneally with 0. A catalystfree aziridine ringopening in spiroaziridineoxindoles by thiophenol in water gives access to 3,3disubstituted 2oxindoles bearing a. Rethinking their application and manipulation in synthesis christopher r. Aziridines are highly versatile intermediates in organic synthesis due to their easy access and their susceptibility to ringopening by facile cn bond cleavage. Aziridines are powerful alkylating agents, whose toxicity is at the origin of their intrinsic in vivo potency. Aziridines, the triangular, comparably highlystrained nitrogen analogues of epoxides, are important synthetic intermediates i.
Among them, azacyclopropanes, commonly referred as aziridines, occupy a prominent place in synthetic organic and medicinal chemistry due to its occurrence in natural resources, complexity involved in synthesis due to ringstrain, building blocks in organic synthesis, and its biological properties. An updated library on the synthesis of aziridines bentham science. Metal free onepot synthesis of morpholine 3a from aziridine 1a. The acidcatalyzed additions in examples 2 and 3, illustrate the influence of substituents on the regioselectivity of addition. Aziridines article about aziridines by the free dictionary. Aziridines and epoxides are among the most widely used intermediates in organic synthesis, acting as precursors to complex molecules due to the strains incorporated in their skeletons. Pdf an improved and mild wenker synthesis of aziridines. Asymmetric synthesis of epoxides and aziridines from aldehydes and imines varinder k. Application of aziridines for the synthesis of isoquinoline. Afagh master of science department of chemistry university of toronto 2010 abstract nalkenyl aziridines are a unique class of molecules that do not behave as typical enamines as a result of the inability of the nitrogen atom lonepair of electrons to delocalize. Alkaline treatment of the products of addition of nucleophilic reagents to ethyl. Aziridine synthesis by aziridination organic chemistry portal. Aziridine is the organic compounds consisting of the threemembered heterocycle ch 2 2 nh.
It has been found for the first time at room temperature that the reaction of an unactivated 2alkyl or 2aryl aziridine with carbon dioxide to generate the corresponding oxazolidinone does not need any form of catalysis or solvent to proceed in high yield, especially when using high speed ball milling. Shaun murphreeb aemory university, atlanta, ga 30322 email. Ozdemir do gan september 2010, 74 pages a systematic study was carried out for the synthesis of aziridine 2phosphonates by using two methods. Their synthetic utility lies in the fact that they can be ringopened with a broad range of nucleo.
Synthesis of aziridines by visiblelight induced decarboxylative cyclization of naryl glycines and diazo compounds springerlink. Metalfree onepot synthesis of 2substituted and 2,3disubstituted morpholines from aziridines hongnan sun, binbin huang, run lin, chao yang and wujiong xia. Recent synthetic applications of chiral aziridines william mccoull,a franklin a. Products obtained from the oxidation of naminophthalimide in the presence of azoalkenes m. Wiley online library tetsuji kametani and toshio honda, application of aziridines to the synthesis of natural products, 10. General transformations of aziridines because aziridines are closely related in structure to oxiranes and cyclopropanes, the approaches to their synthesis are very similar. Since polyfunctional aziridines are trifunctional and the acrylic emulsion of polyurethane dispersion can be multifunctional, a crosslink density or network is formed through this reaction mechanism. However, if the aziridine ring is incorporated in a larger organic. Aziridines and epoxides in organic synthesis wiley online books. The physical and chemical properties of acrylic emulsion or polyurethane dispersion based coatings, inks, and adhesives are increased due to. Azaheterocyclic compounds are wellknown to have diverse types of biological activity.
Aziridines are useful intermediates in organic chemistry due to their highly strained ring systems which allow for a wide range of reactivity. Direct stereospecific synthesis of unprotected nh and n. Download hires imagedownload to mspowerpointcite this. Pdf synthesis of new bicyclic aziridines containing. Aziridines and azirines are the simplest of the heterocyclic ring systems containing nitrogen, containing just two carbon atoms and one nitrogen. There have been few reports on the ringopening reactions of nalkylaziridines.
Jessing 1 n r activated aziridines r co2r, so2r and cor nonactivated aziridines r h, alkyl and aryl ho nh2 o so nh 2 o o n h aziridines can be synthesized in numerous ways including sn2 displacement, 14 addition, addition of carbenes, electrophiles, nitrenes and reduction h. Recently, we developed a metalfree protocol for primary amination. The geometry, energy, strain energy, and inversion barrier of 2methyleneaziridine and 2,3bismethyleneaziridine were calculated and compared with similar information on aziridine itself. Unexpected synthesis of aziridines under cui catalyzed kinugasa. Method selection for trace analysis of potentially. Several drugs feature aziridine rings, including mitomycin c, porfiromycin, and azinomycin b carzinophilin. Jessing 1 n r activated aziridines r co2r, so2r and cor nonactivated aziridines r h, alkyl and aryl ho nh2 o so nh 2 o o n h aziridines can be synthesized in numerous ways including sn2 displacement, 14 addition. Investigation of methods for the synthesis of aziridines and. The toxicology of a particular aziridine compound depends on its structure and activity, although sharing the general characteristics of aziridines. Aziridine formation occurs through aminobromination and subsequent baseinduced ring closure. Pdf aziridines are important precursors for the synthesis of various nitrogencontaining bioactive. Ethyleneimine, stabilized appears as a clear colorless liquid with an ammonia like odor. The parent compound is aziridine or ethylene imine, with molecular formula c 2 h 4 nh.
Aziridines are important precursors for the synthesis of various nitrogencontaining bioactive molecules, such as heterocycles, alkaloids and amino acids. Free energy profiles and relative energies along the reaction coordinate for pathways a. We chose the 1,3dipolar cycloaddition of azomethine ylides generated from aziridines as the model reaction. Aziridine is a saturated organic heteromonocyclic parent, a member of aziridines and an azacycloalkane. Given this simplicity in terms of structure, aziridines. A highly efficient rhiicatalyzed direct preparation of unactivated aziridines from olefins relies on o sulfonylhydroxylamines as the aminating agents. Aziridines and azirines with exocyclic unsaturation have also been the subject of theoretical studies. The majority of methods for the preparation of aziridines mimic the highly developed syntheses of epoxides5 or cyclopropanes. First method is the classical gabrielcromwell reaction and the. Angewandte highlights aziridine synthesis new catalysts. Pdf the conventional wenker synthesis of aziridines from vicinal amino alcohols has been modified by employing. Aziridines are the fully saturated example of this heterocyclic ring system, while azirines contain a single double bond. Aziridines are organic compounds containing the aziridine functional group, a threemembered.
1429 571 1333 1476 1310 1006 402 758 1480 103 28 1 1494 889 740 1326 1302 1508 1186 29 510 567 1291 468 820 1435 1384 310 666 1407 1052