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. Abstract synthesis of imidazolines from aziridines by michael robert kuszpit the majority of the work in this thesis presents a new method to syntheisize imidazolines. Publications aggarwal research group school of chemistry. To learn more about polyaziridine products, contact a. Recently, the utilization of biological systems has emerged as a novel method for the synthesis of nanoparticles. These approaches have many advantages over chemical, please purchase pdf split merge on. The reaction of the budam imine 48 scheme 1 and ethyl diazoacetate 12 with the vanol catalyst gives the cisaziridine 49 in 97% yield and 98% ee scheme 4. Synthesis of functionalized indenes via cascade reaction of. Ecological information ecological data for aziridine, 2methyl bioaccumulation does not bioaccumulate. The original wenker synthesis of aziridine itself takes place in two steps.
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. A second subsection dedicated to the synthesis of optically pure c2,3disubstituted naryl and nh cisaziridines was achieved by means of a chiral binolderived ntriflylphosphoramide bronsted acid catalyst. Aziridine is a saturated organic heteromonocyclic parent, a member of aziridines and an azacycloalkane. Example 4 demonstrates that this approach to azetidine formation works well in the absence of competition. Amino acid synthesis by aziridine ring opening reaction is a good example to the use of. Pz33 is an ethylene imine based trifunctional polyaziridine with a functionality of 3. First synthesis of aziridines using polymersupported triphenylphosphine isabelle mccort, ste.
Synthesis and applications of vinylaziridines and ethynylaziridines. Direct transformation of epoxides to 1,2diacetates with ac2oboh3 system aziridines are useful intermediates in organic chemistry due to their highly strained ring systems which allow for a wide range of reactivity. Ethyleneimine aziridine 151564 hazard summary ethyleneimine has many uses, including in polymerization products and in adhesives and binders. Two alternative and complementary onepot procedures for the direct transformation of 2amino alcohols to n tosyl aziridines are presented. With this in mind, we have used nalkyl aziridines in a regio and stereochemically controlled synthesis of polycyclic heterocycles based on nucleophilic ring opening and subsequent intramolecular cyclization.
The majority of methods for the preparation of aziridines mimic the. Chiral aziridines are structure units found in many biologically active compounds and are important building blocks in organic synthesis. Rethinking their application and manipulation in synthesis christopher r. Synthesis of chiral 12aminoalkylaziridines via a self. This is a good example of thekinetic advantage of threemembered ring formation. However, this reaction has been described in only a few papers and concerns specific reactions, namely, the synthesis of complexes of aziridines with transition metals.
Davis b a astrazeneca, mereside, alderley park, macclesfield, cheshire, sk10 4tg, uk. Ethyleneimine, stabilized appears as a clear colorless liquid with an ammonia like odor. General characteristics epoxides can be converted into aziridines by nucleophilic attack of azide ion, the staudinger reaction, and aziridine ring formation with. Less hindered aziridines can be obtained in high yields by tosylation and in situ cyclization effected by potassium hydroxide in waterdichloromethane. We became interested in the synthesis of aziridines from the reactions of imines with diazo compounds mediated by a lewis acid.
Synthetic applications of nh aziridine containing compounds. Epoxidation and aziridination of carbonyl groups and imines. Polyfunctional aziridine supplier polyaziridine llc. Wulff, highly diastereoselective alkylation of aziridine. The aziridine ringopening reaction with aziridine itself23 has been known for a long time in coordination chemistry and was named dimerization of aziridines. Indeed, the exceptional yield of this product is attributed to the gemdimethyl. Polyaziridine crosslinkers show a positive ames test whereas a certain percentage of general users develop allergic reactions when applying this crosslinking system.
The synthesis and applications of nalkenyl aziridines nicholas a. Aziridine moieties occur in many natural products and are also encountered in unnatural biologically active compounds including drugs in clinical use, especially in the field of cancer treatment. Synthetic applications of nh aziridine containing compounds shannon marie decker master of science department of chemistry university of toronto 2010 abstract unprotected nh aziridine aldehydes are surprisingly stable compounds which can undergo reactions in the absence of protecting groups. Aziridines are highly useful compounds as building blocks for the synthesis of important organic compounds. Application of aziridines for the synthesis of isoquinoline. The first report of general method for the generation of an aziridine from the reaction of an imine and ethyl diazoacetate with simple lewis acids appeared in. Aziridine2,3dicarboxylate inhibitors targeting the major. Recent synthetic applications of chiral aziridines william m c coull, a franklin a. Aziridines are very useful intermediates for the synthesis of numerous nitrogencontaining biologically active compounds 1,2,3. The aziridine end groups can react with active hydrogen as found on carboxyl. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Polyaziridine llc is dedicated to providing a complete line of polyfunctional aziridine crosslinkers and creates a unique partnership with customers to provide necessary technical support. Linear polyethyleneimine was synthesized by the cationic ringopening polymerization of n2tetrahydropyranyl aziridine, followed by acidic hydrolysis of the corresponding substituted polyamine. Goups of 56 male dowwistar rats were injected intraperitoneally with 0.
This salt is then reacted with sodium hydroxide in the second step forming aziridine. The linear structure of the end product was proved by cnmr spectroscopy and by its physical properties. Synthesis and nucleophilic opening of a new c 2 symmetric bisaziridine. Merging photoredox with 1,2metallate rearrangements. The observed excellent yields, regioselectivities and enantioselectivities find no rivals in other organocatalytic aziridine synthesis. Pdf carbonylation of aziridines as a powerful tool for.
Aziridines as intermediates in diversityoriented syntheses. Inhalation and exposure to aziridine, severe respiratory irritation, throat inflammation, and edema in lungs appear. Pz33 polyfunctional aziridine specs polyaziridine llc. Entry compound r1 zr2 yield, % 1 2a c6h5 nbunh 79 2 2b c6h5 58 3 2c 2,5meo2c6h3 nbunh 75 4 2d 2,5meo2c6h3 nhexnh 69 5 2e 2clc6h4 nbunh 92 6 2f 2clc6h4 nhexnh 73 7 2g 2clc6h4 61 8 2h 2clc6h4 ome 76 9 2i 2no2c6h4 nbunh 71 10 2j 2no2c6h4 ome 57 11 2k nbunh 50 figure. Synthesis and reactivity of 2carboxymethylaziridine. Aziridine is an organic compound consisting of the threemembered heterocycle ch 2 2 nh. In the areas of medicinal chemistry and chemical biology, aziridines are of current interest as starting materials for the preparation of peptides and the synthesis of peptidelike compounds. Aldimines generated in situ from aldehydes and amines react readily with ethyl diazoacetate in the presence of 2 mol% of biotf 3 in bmimpf 6 to produce the corresponding aryl aziridine carboxylates in high yields with excellent cisdiastereoselectivity. A mild and regioselective ringopening of aziridines with.
Increased angle strain in aziridine is also responsible for increased barrier for nitrogen inversion. This barrier is high enough for the isolation of separate invertomers for instance the cis and trans invertomers of nchloro2methylaziridine. The photochemical alkylation of vinyl boronate complexes. Synthesis and reactivity of 2 carboxymethylaziridine derivatives. Drosophila melanogaster carcinogenicity rat, malefemale, oral, 28 weeks, daily positive 12. Polyfunctional aziridine pz28 pz28 is a propylene imine trifunctional polyaziridine that is used in both aqueous and nonaqueous coatings, inks, and adhesives to promote both physical and chemical properties. Pdf mono and disubstituted aziridines derived from sterically hindered olefins of the. The synthesis of n tosylaziridines 7 was accomplished by basemediated cyclization of bistosylates 6 of 2amino alcohols 5 in water and dichloromethane in equal amounts scheme 1. Towards this end, several di and trisubstituted aliphatic olefin and styrene substrates entries 2933, fig. Optimized conditions are described for the synthesis of 1trityl2 aziridine carboxylic acid 3 trtazyoh and benzyl 2s aziridine 2carboxylate 6 hazyobzl as useful derivatives for the. Aziridines article about aziridines by the free dictionary. Jul 02, 2009 the efficient synthesis of small molecules that collectively comprise optimal smallmolecule screening collections is an important goal. Synthesis and nucleophilic opening of a new symmetric bis.
Catalytic asymmetric synthesis of trisubstituted aziridines. Studies have been made on the possible synthesis of 1 arylethynylaziridines by oxidative condensation of phenylacetylene with aziridine and by alkylation of aziridine with 1halo2arylacetylenes. Among the variously functionalized aziridines,1 vinylaziridines and ethynylaziridines are. Nitrogen heterocycles aziridines cycloaddition carbon dioxide fixation zwitterions 1,3dipoles chemistry based on ring opening of aziridines has been widely studied in organic synthesis. And, not have a methyl group attached to the aziridine ring it is the fastest reacting polyfunctional aziridine crosslinker. 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. 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. Sequential catalytic asymmetric aziridination and aziridine alkylation reactions have been applied to the synthesis of birt. Preparation and reactions of heterocyclic compounds i. The synthesis of ntosylaziridines 7 was accomplished by basemediated cyclization of bistosylates 6 of 2amino alcohols 5 in water and dichloromethane in equal amounts scheme 1. Aziridines can be prepared in organic synthesis in several ways. Visible lightdriven strainincrease ring contraction allows the synthesis of cyclobutyl boronic esters.
Synthesis of functionalized indenes via cascade reaction of aziridines and propargyl alcohols. A first section includes introduction part for all the subsections listed below where as second section will give more insight on the result and discussion. Carbonylation of aziridines as a powerful tool for the synthesis of functionalized. New synthesis of linear polyethyleneimine springerlink.
Synthesis and reactivity of 2 carboxymethylaziridine. Optimized conditions are described for the synthesis of 1trityl2aziridinecarboxylic acid 3 trtazyoh and benzyl 2saziridine2carboxylate 6 hazyobzl as useful derivatives for the. Aziridine2,3dicarboxylate inhibitors targeting the major cysteine protease of trypanosoma brucei as lead trypanocidal agents radim vicik,a verena hoerr,a,b melanie glaser,b martina schultheis,d elizabeth hansell,c james h. Despite this unfavourable toxicity profile, the use of aziridine crosslinkers still survives due to the versatility of the. 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. Aziridine 1 continues to be the focus of many molecular orbital calculations, particularly hf, scf, mp2, and mp3 ab initio methods using a wide variety of basis sets, thus providing data on the geometry, energy, and bond order of this molecule. Complete experimental procedures and compound characterization data pdf.
Merging these two interesting chemical building blocks can lead to a fascinating structural motif named spiroaziridinepyrrolines sap, which has been. Aziridine synthesis overview n x r1 r2 x n r2 mln r1 x n r2 r1 y r1 r2 tiiv phinx h o oh r 1 r 2 h 2nx socl 2, o o r1 r2 mn 3 pph 3 x n r2 br r2 r1 h 2nx r1 br r 4px socl 2, rso 2cl h nhx r r i. Ring opening of oxiranes using azide followed by pph3 reduction of the intermediate azido alcohol to give the corresponding aziridines. Yudin, aziridines and epoxides in organic synthesis, wileyvch, weinheim 2006. The synthesis and applications of nalkenyl aziridines. Pdf carbonylation of aziridines as a powerful tool for the. Aziridines can be synthesized in numerous ways including sn2 displacement, 14 addition, addition of carbenes, electrophiles, nitrenes and reduction h. Lactams article pdf available in european journal of organic chemistry 201740. 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. In the first step ethanolamine is reacted with sulfuric acid at high temperatures 250 c to form the sulfate monoester.
It is highly toxic to the skin and causes irritation to the eyes. Coppericatalyzed asymmetric decarboxylative mannich reaction. A similar sequence, using a chiral aziridine, was employed as a key reaction in a novel synthesis of. Furthermore, the incorporation of an electrophilic aziridine moiety in peptide or peptidomimetic frameworks is an interesting strategy for the design of active sitedirected drugs, especially in the field of chemotherapy 6,7. 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. Wenker synthesis is a typical method for synthesis of aziridines in which 2amino alcohols from natural or synthetic amino acids are cyclized by base. Acute shortterm inhalation exposure to ethyleneimine causes severe respiratory tract irritation and inflammation in humans, but symptoms may be delayed for several hours. In the areas of medicinal chemistry and chemical biology, aziridines are of current interest as starting materials for the preparation of peptides 23 and the synthesis of peptide. Synthesis of 2carboxymethylaziridine derivatives in the following section, synthesis of 2carboxymethylaziridine derivatives will be dealt with.
Azaheterocyclic compounds are wellknown to have diverse types of biological activity. Facile synthesis of novel spiroheterocycles via diastereoselective. General transformations of aziridines because aziridines are closely related in structure to oxiranes and cyclopropanes, the approaches to their synthesis are very similar. Branched amine synthesis via aziridine or azetidine opening with. Polyaziridine is committed to being the source of this technology in the crosslinker market. Pdf synthesis and transformations of 2adamantan1ylaziridine. Threecomponent synthesis of highly functionalized aziridines.