DOCSLIB.ORG

Studies Directed Towards the Synthesis of Novel Naturally Occurring Alkaloids

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Studies Directed Towards the Synthesis of Novel Naturally Occurring Alkaloids i l STUDIES DIRECTED TOWARDS THE SYNTHESIS 1 OF NOVEL NATURALLY OCCURRING ALKALOIDS I I .tI t I I I i A THESIS I i PRESENTED FOR THE DEGREE OF I ,I DOCTOR OF PHILOSOPHY i i L IN THE UNIVERSITY OF ADELAIDE fi,.7,,.¡¿,¡p{<-./ iç ' 'l - ¡Î :' BY BRUNO KASUM, B,Sc. DepRRrmeNT oF OnsRtruc CHEmISTRy 1984 CONTENTS Page SUMMARY (i) STATEMENT (Íii) ACKN0I¡ILEDGEMENTS (iv) CHAPTER 1 A CLASSICAL APPROACH TO THE SYNTHESIS OF PERLOLINE I NTRODUCTION I DISCUSS ION 7 1.1 Synthesis of the Diphenyìamine Synthon (4) 7 1.1.1 Reamangement of 3-Al kyl -3-aryl -L-(2' o carboxyphenyl ) tri azenes J 1.1.2 Reanrangement of a,N-Diphenylnitrones t4 7.2 Synthesis of the 4-bromo-2-oxo-1,2- di hydropyri di ne-3-carboxy] i c aci d synthon ( 5) 23 CHAPTER 2 2.L Attempts to form the Tertiary Amide (a2) 31 2.2 Metallation of Diphenyìamine (4) and reaction with Ethyl 3-chloro-2-cyanobut-2-enoate (34) 36 2.3 Alternative Routes to Dehydroperloline from 2- ( 3 ,4-Dimethoxypheny'l ami no ) acetophenone 43 CHAPTER 3 SYNTHETIC ROUTES TO A NOVEL MARINE SPONGE ALKALOID INTRODUCTION 47 DISCUSSION 55 Page 3.1 Approaches from Hagemann's Ester 55 ac A Procedure from 2-Nitrodimedone 60 3.3 Routes based on the Cyclisation of Intermediates derived from 5,S-Dimethyl -3- ( 2-dimethyì ami noethenyl ) -2-cycl ohexen-1- one (47) 63 CHAPTER 4 4.L Synthesis of the 7.0x0-4,5,6,7-tetrahydroindole precursor and Attempted Ring Expansion 7T 4.2 An Alternative Route from 2,3-Epoxy-3- methyl cyc'l ohexanone oxime 88 4.3 A Final Approach from 4-Methyl-Z,5,6,7- tetrahydro-lH-azepi n-2-one ( 13) 92 4.4 Synthesis of the Pyrro'loazepindione precursor (3) from 3-N-(2-pyrrolylcarbonyl )amino- propanoic Acid (17) 96 CHAPTER 5 EXPERIMENTAL 702 5.1 l'lork described in Chapter I 105 5.2 l^lork described in Chapter 2 I23 5.3 l^lork described in Chapter 3 L42 5.4 l¡Jork described in Chapter 4 151 REFERENCES 18t PUBL I CATIONS 198 (i ) SUMMARY Chapters I and 2 describe a convergent approach to the synthesis of dehydroperloìine, a precursor of the naturalìy occurring alkaloid perloline. Chapter 1 deals with the preparation of N-(2-bromophenyì ) (3,4-djmethoxyphenyl )amine and 4-methoxy- 2-oxo-1,2-dihydropyridine-3-carbox_v'l ic acid. The diphenyla¡nine was prepared by thermal rearrangement of N-(2-bromophenyì)-2- (3,4-dimethoxyphenyì )oxaziridine derived from the appropriate nitrone. The synthesis of various 4-substituted-2-oxo-I,2- dihydropyridine-3-carboxy'lic acids in high yields from 3-halo or alkoxy-2-cyanobut-2-enoates is also described. Chapter 2 deals wjth various uirsuccessful attempts at coupling the above two synthons by formation of a tertiary amide. The bulkiness of the diphenyìamine apparent'ly precluded the synthesis of the required arnide. This chapter also includes the reaction of the dilithiated diphenylamine vrith ethyl 3-chloro-2- cyanobut-2-enoate. The final ring closure to form the tertiary amide could not be accompìished. An alternative unsuccessful strategy based on the Knoevenagel reaction of ethyl cyanoacetate with 2-(3,4-dimethoxyphenyiamino)acetophenone is aìso discussed. (ii) Chapters 3 and 4 describe synthetic routes to a novel marine sponge alkaloid containing a fused pyrrote-azepinone ring system linked to a glycocyamidine moiety. chapter 3 discusses a variety of approaches to one precursor from substituted methylcyclohexenones such as isophorone and Hagemann's ester. Although unsuccessful these approaches yie]ded interesting results. chapter 4 descrÍbes a successful route to an arternative precursor, 7-oxo- I -phenyl methy'l -4, 5,6, 7-tetrahydroi ndol e based upon the heteroannelation of 2-amino-3-methyl -2-cyclohexen-1-ones with dimethyìformamide dimethyì acetal. However, ring expansion of the ketone could not be achieved. Alternative routes such as the attempted heteroannelation of 4-methyl-3-pheny]methylamino- 2,5,6,7-tetrahydro-(lH)-azepin-2-one and the oxime of 3-methyl-z- phenylmethylamino-2-cyclohexen-1-one are described also. A successful synthesis of pyrrolo[4,5]azepin-6,10-(lH)-dione is presented in the last section of chapter 4. This precursor was amived at by the cycl ization of 3-N-(2-pyrrolytcarbony'l)amino- propanoic acid in po'lyphosphoric acid. The condensation of the precursor dione with gìycocyamidine proceeded aLbeit in very poor yieìd. The final dehydration of this aldol product to the naturaìly occurring compound has not yet been achieved. (iii) STATEMENT This thesis contains no material previously submitted for a degree or diploma in any University and to the best of my knowledge and belief, contains no material previously published or written by another person, except where due reference is made in the text. BRUNO KASUM (iv) ACKNO}ILEDGEMENTS I would sincere'ly ìike to thank my supervisor, Dr. R.H. Prager, for his guidance, encouragement and enthusiasm during the course of this work. The helpful assistance. and suggestions from other members of the Department, particularly Dr. A.D. hlard are also acknowledged. This research was conducted during the tenure of a Commonwealth Postgraduate Award, for which I am grateful. Finally, I would like to thank my parents for their understanding and support during the course of my studies. INTRODUCTION I INTRODUCTION The alkaloid perlolinel (1) found in perenniat r"yu grurr* (zoLiun perenne L. ) and tall fescue (Festuca arundinacnù? nu, recently become of great interest both as a synthetic target and because of its pharmaco'logica'l propenuies.3 OMe H H (1) (2) Perìolidine (2), a minor alkaloidaì component of rye grass, has also been isolated4 from 2,. perewrc, and to date four syntheses have been published.5-7 The synthesis of perloline has been reportedS as well as mild oxidations which have produced a colourless non basic material, dehydroperloline9 (3), the subject of the synthetic work described in the first part of this thesis. * Also called New Zealand rye grass or Engìish rye grass in Chem.Abstr. 2 H (3) Perloline has been linkedlO with the condition known as "rye grass staggers"ll observed in sheep and cattle grazing pastures consisting soìe'ly of rye grass seedlings or new shoots.10 Rye grass from these pastures contains a much higher alkaloid content (0.15-0.25%) than more mature grass (0.02-0.06%) which contains most'ly per'loìine. Parenteral administration of perìoline to guinea pigs and sheep at dose levels similar to those found in sheep grazing on rye grass, produces effects resembling symptoms of rye grass staggers. However, ora'l administration of perloline (1C0-200 mg/kg) produces the symptoms in guinea pigs but not in ,h..p.10 Recent work has shown that corynetoxins, formed in gaìled seeds of noLim rìgidwn (annual rye grass) a related species, by a bacteri um Corynebacteriun rathayi and a nematode , Anguina agrostis, are responsibìe for annual rye grass toxicity.12'13 However it is still unclear whether similar toxins are responsible for the staggers condition associated with perennial rye grass. 3 Since perloline occurs only in small quantities in rye grass, an efficient synthesis would encourage further research into its physioìogical activity. Although dehydroperloline has been recently synthesizedS'14 in this department it was the aim of this work to develop a highly convergent route to this compound and hopefuìly open some new areas of chemistry in the process. Dehydropertoline v,,as chosefas a more suitable target because of its greater stability and the fact that reduction under very mild conditions leads to the naturally occurring alkatoi¿8 (f). 4 A hypothetical dissection of the dehydroperloline molecule, shown in Scheme 1, suggested that a convergent synthesis was plausible from two relativeìy smaller fragments: the substituted diphenylamine (4) and 2-oxopyridinecarboxylate (5Ifhese 2 compounds Me Me (3) H Br OMe ET N H H Br (4) (5) SCHEME 1 r¡,ere accordingly chosen as the next most suitable sub-targets. Compounds (+) and (5) coutd theoretically be reunited in three di sti nct !,,ays: 5 1) simultaneous formation of amide and aryl-aryl bonds 2) formation of aryl-aryl bond prior to amide bond 3) formation of amide bond then aryl-aryl bond. All three methods were investigated during the course of this work. Although a variety of methods exist in the literature for the formation of amides,15 methods for aryl-ary'l bond formation are not as common. The first approach considered was that of 3) above. Thus if the amide bond was constructed first, compound (6) should be formed. OMe (6) SCHEME 2 An Ulìmann type coupling reaction uti'lizing one of the many coup'ling reagents known16 was expected to produce dehydroperloline (3) (Scheme 2). Ullmann coupling reactions of 4-halopyridines with other 4-halopyridines have been reported,lT'18 as has the intramolecular coup'ling of aryì halides.l9 An interesting alternative to the Ulìmann reaction could be the reductive coupling of (7) with lithium aluminium hydride, although 6 the relative rates of amide reduction versus aryl halide reduction remain to be determined. OMe OMe ( c I tl o H (7) An analogy to this type of coupling has been reported with z-Z..chlorostilbene to give phenanthnene.20 D I SCUSS ION 7 1.1 Synthesis of the Diphenvlamine Svnthon (4) Aìthough there are several routes to diphenylamines available in the ìiterature, the most widely used are the Chapman rearrangement?l-z4 and the Ullmann condensation?S'26 The Chapmun2T ,.urrangement involves the thermal rearrangement of N-ary'lbenzimidates (8) to N-aroyldi- pheny'lami nes (9) ( Scheme 3) .
Load more

Recommended publications
  • Synthesis and Antitumor Activity of Some Novel Thiophene, Pyrimidine, Coumarin, Pyrazole and Pyridine Derivatives
    Acta Pharm. 67 (2017) 15–33 Original research paper DOI: 10.1515/acph-2017-0004 Synthesis and antitumor activity of some novel thiophene, pyrimidine, coumarin, pyrazole and pyridine derivatives MOHAMMED ALBRATTY1 2-Cyano-N-(thiazol-2-yl) acetamide (2a) and 2-cyano-N-(oxazol- 1,2 KARAM AHMED EL-SHARKAWY * 2-yl) acetamide (2b) were obtained via the reaction of ethyl cya- SHAMSHER ALAM1 noacetate with either 2-aminothiazole (1a) or 2-aminooxazole 1 Department of Pharmaceutical (1b). The formed products were directed toward the reaction Chemistry, College of Pharmacy with cyclopentanone and elemental sulfur in the presence of Jazan University, P.O. Box 114 triethylamine to give cyclopenta[b]thiophene derivatives (3a,b). Jazan 45142, Saudi Arabia The latter products were reacted with either ethyl cyanoacetate or malononitrile to form compounds 4a,b and 5a,b, respectively. 2 Department of Organic Chemistry Compounds 4a,b were aimed at synthesizing some heterocyclic Faculty of Biotechnology compounds; thus internal cyclization reactions were intro- October University for Modern duced to form compounds 6a,b. Also, compounds 4a,b reacted Sciences and Arts (MSA) with salicylaldehyde, hydrazine derivatives and either urea or El-Wahat Road thiourea to produce coumarin derivatives (7a,b), pyrazole de- 6 October City, Egypt rivatives (8a-d) and pyrimidine derivatives (9a-d), respectively. Reaction of either benzaldehyde or benzene diazonium chlo- ride (11) with compounds 4a,b afforded compounds 10a,b and 12a,b, respectively. On the other hand, compounds 5a,b under- went internal cyclization to form pyrimidine derivatives 13a,b. Also, when compounds 5a,b reacted with either ethyl cyanoac- etate or malononitrile, they gave pyridine derivatives (15a-d) through the formation of intermediates (14a-d).
    [Show full text]
  • Synthesis of the Caffeine Metabolites 5-Acetylamino-6-Formylamino- 3-Methyluracil (AFMU) and 5-Acetylamino-6-Amino-3-Methyluracil (AAMU) on a Preparative Scale R
    Synthesis of the Caffeine Metabolites 5-Acetylamino-6-formylamino- 3-methyluracil (AFMU) and 5-Acetylamino-6-amino-3-methyluracil (AAMU) on a Preparative Scale R. Röhrkasten3, P. Raatz3, R. P. Kreher3*, M. Blaszkewiczb a Lehrstuhl für Organische Chemie II, Fachbereich Chemie, Universität Dortmund. D-44227 Dortmund b Institut für Arbeitsphysiologie an der Universität Dortmund, ZWE Analytische Chemie, Ardeystraße 67, D-44139 Dortmund Z. Naturforsch. 52b, 1526-1532 (1997); received April 7, 1995 Pyrimidine-diones, Caffeine Metabolites, Synthesis 5-Acetylamino-6-amino-3-methyluracil (AAMU) and 5-acetylamino-6-formylamino-3- methyluracil (AFMU) have been prepared by simple chemical transformations starting from thiourea and ethyl cyanoacetate. These compounds AAMU and AFMU are required as standard materials for qualitative identification and quantitative determination in connection with the metabolism of caffeine. Introduction procedures are applied to obtain weighable amounts. The first method consisted in the con­ The N-acetyltransferase plays an important role sumption of a caffeinated beverage and the extrac­ in the metabolism of many xenobiotics; the pro­ tion of the metabolites from the urine; but the duction of the enzyme is genetically controlled. In­ yields are low [10]. A very expensive synthetic dividuals differ in the amount of the acetylated procedure is based on a procedure of Khmelevskii metabolites and can be classified as slow or rapid et al. [3] modified by Tang et al. [10] using 1-MU acetylators. The acetylator status is connected with instead of uric acid. After acylation with formic some diseases such as diabetes mellitus and blad­ acid/acetic anhydride the yield was only 19% pro­ der cancer and the knowledge of it is for the bene­ ducing 2 mg of AFMU 9.
    [Show full text]
  • Synthesis of Biologically Important Pyrrole Derivatives in Any 13C and 15N Isotope Enriched Form by Prativa B
    Global Journal of Science Frontier Research Chemistry Volume 12 Issue 2 Version 1.0 February 2012 Type : Double Blind Peer Reviewed International Research Journal Publisher: Global Journals Inc. (USA) Online ISSN: 2249-4626 & Print ISSN: 0975-5896 Synthesis of Biologically Important Pyrrole Derivatives in Any 13C and 15N Isotope Enriched Form By Prativa B. S. Dawadi & Johan Lugtenburg Leiden University, Leiden Abstract - Recently the synthesis of [3-13C]-, [4-13C]-, and [11-13C]- porphobilinogen, [15N,13C4]-1H - pyrrole-2,3,5 - tricar - boxylic acid, [1-15N]-3-cyano-4-methyl-1H-pyrrole and [2-13C]- and [3-13C]-cyano-4- methyl-3-pyrrolin-2-one have been published. Incorporation of 13C and 15N in these systems at any position and combination of positions has become accessible. Also mild alkylations of active methylene compounds with α-halo carbonyl compounds open up many 3-pyrrolin-2- ones and pyrrole systems based on stable isotope building blocks that have been published. This gives the access to a whole new library of stable isotope enriched pyrroles in any stable isotope enriched form. This is also the case for biliverdin IXα which after enzymatic treatment has been converted into (2R)-phytochromobilin that reacts with its apoprotein to form intact active phytochrome. Keywords : [1-15N]-3-Cyano-4-methyl-1H-pyrrole, [3-13C], [4-13C]-, and [11-13C]-porphobilinogen, [ 15N, 13C4,] -1H-pyrrole-2,3,5-tricarboxylic acid and biliverdin IXα. GJSFR -B Classification: FOR Code: 030503, 040203, Synthesis Of Biologically Important Pyrrole Derivatives In Any 13C And 15N Isotope Enriched Form Strictly as per the compliance and regulations of: © 2012.
    [Show full text]
  • Route of Knoevenagel Reaction from Conventional Method to Greener Methods
    IOSR Journal of Environmental Science, Toxicology and Food Technology (IOSR-JESTFT) e-ISSN: 2319-2402,p- ISSN: 2319-2399.Volume 9, Issue 12 Ver. I (Dec. 2015), PP 52-55 www.iosrjournals.org Route of Knoevenagel Reaction from Conventional method to Greener methods Dr. Leena H. Sarkar Department of Chemistry, J.V.M’s Degree College, Airoli, Navi Mumbai 400 708, India. Abstract: In the past few years, classic methods of synthesis have been replaced by newer methods of synthesis involving principles of Green Chemistry given by Anastas and Warner leading to environmentally safer products and processes and reducing pollution and thus making the environment greener. In this review article I have compared old classical method of Knoevenagel reaction with greener methods for a more sustainable, pollution free future society. Key Words: Green chemistry, Knoevenagel reaction, solvent free reactions, sustainable chemistry, use of ultrasound radiations, catalysis, microwave chemistry and use of ionic liquids. I. Introduction The Knoevenagel [1] reaction is considered to be a modification of the aldol reaction [2]. It is named after Emil Knoevenagel. It is a condensation reaction of aldehydes or ketones 1 with active methylene compounds 2 in presence of base like ammonia or another amine or piperidine as a catalyst in organic solvents to yield α,β-unsaturated carbonyl compounds 3 (Fig. 1) which serve as intermediates in various reactions and compounds of medicinal interest [3-7]. Group attached to methylene group must be powerful enough to facilitate deprotonation to form enolate ion, even with a mild base. Fig. 1: Conventional method of Knoevenagel synthesis II.
    [Show full text]
  • Reactive Polymers Fundamentals and Applications
    Propery of Reed Elsevier 13 Cyanoacrylates Cyanoacrylates were commercially introduced in for polymerization. Instead of aqueous formaldehyde, 1950 by Tennesee Eastman Company. Cyanoacrylate paraformaldehyde was used with an organic solvent to adhesives are monomeric adhesives. They are gener- remove the water by azeotropic distillation. The sta- ally quick-setting materials which cure to clear, hard bility of the monomer can be enhanced by the redistil- glassy resins, useful as sealants, coatings, and par- lation of the crude monomer in the presence of small ticularly adhesives for bonding together a variety of quantities of acidic stabilizers, e.g., sulfur dioxide. substrates [1]. Polymers of alkyl 2-cyanoacrylates are Several other methods for cyanoacrylate monomer also known as superglues. production have been described, including the pyro- In addition to their use as adhesives, cyanoacrylates lysis of 3-alkoxy-2-cyanopropionates [8], transester- have been reported to have highly herbicidal prop- ification of ethyl cyanoacrylate [9], and displacement erties, as they disrupt photosynthetic electron trans- of cyanoacrylate monomer from its anthracene Diels- portation [2–4]. Alder adduct by treatment with maleic anhydride. This last method is used for the synthesis of monomers 13.1 Monomers that are not accessible or may be difficult to prepare by the retropolymerization route, for example difunc- 13.1.1 Synthesis tional cyanoacrylates [10], thiocyanoacrylates [11], and perfluorinated monomers. In 1895 von Auwers and Thorpe [5] attempted to synthesize diethyl-2,2-dicyanoglutarate (Figure 13.1) by base-catalyzed condensation of aqueous formalde- 13.1.2 Crosslinkers hyde and ethyl cyanoacetate. They isolated a mixture To improve the cohesive strength, difunctional mono- of oily oligomers and an amorphous polymer of higher meric crosslinking agents may be added to the mono- molecular weight.
    [Show full text]
  • Classical Antifolates: Synthesis of 5-Substituted, 6-Substituted and 7-Substituted Pyrrolo[2,3-D]Pyrimidines As Targeted Anticancer Therapies Yiqiang Wang
    Duquesne University Duquesne Scholarship Collection Electronic Theses and Dissertations 2013 Classical Antifolates: Synthesis of 5-Substituted, 6-Substituted and 7-Substituted Pyrrolo[2,3-d]Pyrimidines as Targeted Anticancer Therapies Yiqiang Wang Follow this and additional works at: https://dsc.duq.edu/etd Recommended Citation Wang, Y. (2013). Classical Antifolates: Synthesis of 5-Substituted, 6-Substituted and 7-Substituted Pyrrolo[2,3-d]Pyrimidines as Targeted Anticancer Therapies (Doctoral dissertation, Duquesne University). Retrieved from https://dsc.duq.edu/etd/1335 This Immediate Access is brought to you for free and open access by Duquesne Scholarship Collection. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of Duquesne Scholarship Collection. For more information, please contact [email protected]. CLASSICAL ANTIFOLATES: SYNTHESIS OF 5-SUBSTITUTED, 6-SUBSTITUTED AND 7-SUBSTITUTED PYRROLO[2,3- d]PYRIMIDINES AS TARGETED ANTICANCER THERAPIES A Dissertation Submitted to the Graduate School of Pharmaceutical Sciences Duquesne University In partial fulfillment of the requirements for the degree of Doctor of Philosophy By Yiqiang Wang May 2013 Copyright by Yiqiang Wang 2013 Name: Yiqiang Wang Dissertation: CLASSICAL ANTIFOLATES: SYNTHESIS OF 5-SUBSTITUTED, 6-SUBSTITUTED AND 7-SUBSTITUTED PYRROLO[2,3-d]PYRIMIDINES AS TARGETED ANTICANCER THERAPIES Degree: Doctor of Philosophy Date Feb 06, 2013 APPROVED & ACCEPTED Aleem Gangjee, Ph.D. (Committee Chair) Professor of Medicinal Chemistry Mylan School of Pharmacy Distinguished Professor Graduate School of Pharmaceutical Sciences Duquesne University, Pittsburgh, Pennsylvania APPROVED Marc W. Harrold, Ph.D. (Committee Member) Professor of Medicinal Chemistry Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania APPROVED Patrick T.
    [Show full text]
  • Download MSDS File
    Safety Data Sheet - Version 5.0 Preparation Date 3/26/2021 Latest Revision Date (If Revised) SDS Expiry Date 3/24/2024 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE AND OF THE COMPANY/UNDERTAKING 1.1 Product Identifier Chemical Name Ethyl Cyanoacetate Catalogue # E905555 1.2 Relevant Identified Uses of the Substance or Mixture and Uses Advised Against Product Uses To be used only for scientific research and development. Not for use in humans or animals. 1.3 Details of the Supplier of the Safety Data Sheet Company Toronto Research Chemicals 2 Brisbane Road Toronto, ON M3J 2J8 CANADA Telephone +14166659696 FAX +14166654439 Email [email protected] 1.4 Emergency Telephone Number Emergency# +1(416) 665-9696 between 0800-1700 (GMT-5) 2. HAZARDS IDENTIFICATION 2.1/2.2 Classification of the Substance or Mixture and Label Elements GHS Hazards Classification (According to EU Regulation 1272/2008 and US OSHA 1910.1200) Acute Toxicity, Oral (Category 4) Acute Toxicity, Inhalation (Category 4) Acute Toxicity, Dermal (Category 4) GHS Hazards Identification (According to EU Regulation 1272/2008 and US OSHA 1910.1200) Signal Word Warning GHS Hazard Statements H302 Harmful if swallowed. H332 Harmful if inhaled. H312 Harmful in contact with skin. GHS Precautionary Statements P261 Avoid breathing dust/fume/gas/mist/vapours/spray P264 Wash hands thoroughly after handling. P280 Wear protective gloves/protective clothing/eye protection/face protection. P301/P312 IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell. P302/P352 IF ON SKIN: Wash with plenty of soap and water P305/P351/P338 IF IN EYES: Rinse cautiously with water for several minutes.
    [Show full text]
  • Ethyl Cynoacetate.Pdf
    Health 1 1 Fire 1 1 1 Reactivity 1 Personal E Protection Material Safety Data Sheet Ethyl cyanoacetate MSDS Section 1: Chemical Product and Company Identification Product Name: Ethyl cyanoacetate Contact Information: Catalog Codes: 10691 Finar Limited CAS#: 105-56-6 184-186/P, Chacharwadi Vasna, RTECS: AG4110000 Sarkhej-Bavla Highway, TSCA: Not available Ta.: Sanand, Dist.: Ahmedabad, Synonym: Cyanoacetic Acid Ethyl Ester Email: [email protected] Cyanoacetic Ester Web: www.finarchemicals.com Ethyl Cyanoethanoate Malonic Acid Ethyl Ester Nitrile Chemical Formula: C5H7NO2 Section 2: Composition and Information on Ingredients Composition: Name CAS #% Ethyl cyanoacetate 105-56-6 99% Section 3: Hazards Identification EMERGENCY OVERVIEW LACHRYMATOR IRRITANT Irritating to skin, eyes, and respiratory system. May have harmful effects if inhaled or swallowed. Avoid prolonged exposure. Do not breathe vapor. Potential Health Effects Skin contact may cause skin irritation with discomfort or rash. Skin absorption may occur in amounts capable of producing toxic effects. Eye contact may cause eye irritation with discomfort, tearing or blurring of vision. Inhalation may cause irritation of the nose and throat with sneezing, sore throat, runny nose, or shortness of breath. Other effects of exposure may include headache, nausea or vomiting. Section 4: First Aid Measures Eye Contact: Check for and remove any contact lenses. IMMEDIATELY flush eyes with running water for at least 15 minutes while keeping eyes open. COLD water may be used. Seek medical attention. Skin Contact: After contact with skin, wash with plenty of water. Gently and thoroughly wash the contaminated skin with running water and non-abrasive soap. COLD water may be used.
    [Show full text]
  • Fisher Scientific Chemical Stockroom Handbook
    Chemical Stockroom Essentials • Fisher Chemical • Fisher BioReagents • Acros Organics Chemical Storage Guidelines Chemical Stockroom Handbook Introduction As the stockroom manager, you are charged with the safe handling of hazardous chemicals every single day. Your responsibilities are far-reaching … extending beyond the storeroom walls to lab personnel, building staff, campus residents and the environment. Fisher Scientific offers this little- big-book of safety resources. Inside you’ll find storage recommendations, chemical compatibility charts, and recommended essential products to stock to accommodate various research applications undertaken by your customers. Table of Contents Introduction........................................................................................................... 2 Incompatibilities by Hazard Class ................................................................... 11 Periodic Table of the Elements .......................................................................... 2 Chemical Incompatibilities ............................................................................... 12 Fisher Chemical* Purity Chart............................................................................ 3 NFPA Hazard Code Ratings .............................................................................. 13 Fisher Chemical Stockroom Essentials .........................................................4-5 Understanding Chemical Labels...................................................................... 14 Fisher BioReagents*
    [Show full text]
  • Design, Synthesis, Molecular Docking and Anticonvulsant Evaluation of Novel 6-Iodo-2-Phenyl- 3-Substituted-Quinazolin-4(3H)-Ones
    Bulletin of Faculty of Pharmacy, Cairo University (2015) 53, 101–116 HOSTED BY Cairo University Bulletin of Faculty of Pharmacy, Cairo University www.elsevier.com/locate/bfopcu www.sciencedirect.com ORIGINAL ARTICLE Design, synthesis, molecular docking and anticonvulsant evaluation of novel 6-iodo-2-phenyl- 3-substituted-quinazolin-4(3H)-ones Mohamed-Kamal Ibrahim, Khaled El-Adl *, Ahmed A. Al-Karmalawy Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt Received 20 July 2014; accepted 11 May 2015 Available online 28 May 2015 KEYWORDS Abstract A new series of 6-iodo-2-phenyl-3-substituted-quinazolin-4(3H)-one (5–12a–b) derivatives Quinazolin-4(3H)-ones; were synthesized, evaluated for their anticonvulsant activity against pentylenetetrazole (PTZ)- 6-Iodoquinazoline induced seizures and maximal electroshock test and compared with the reference drugs phenobar- derivatives; bital sodium and methaqualone. The neurotoxicity was assessed using rotarod test. The molecular Anticonvulsant agents docking was performed for all the synthesized compounds to assess their binding affinities to GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling were correlated with those obtained from the biological screening. Compounds 9a, 9b, 12a and 7a showed the highest anticonvulsant activities of this series with relatively low neurotoxicity and low toxicity in the median lethal dose test when compared with the reference drugs. The obtained results proved that the most active compounds could be a useful model for future design, adaptation and investigation to construct more active analogs. ª 2015 Production and hosting by Elsevier B.V.
    [Show full text]
  • Recent Synthetic Methodologies for Pyrimidine and Its Derivatives
    Turkish Journal of Chemistry Turk J Chem (2018) 42: 1421 – 1458 http://journals.tubitak.gov.tr/chem/ © TÜBİTAK Research Article doi:10.3906/kim-1806-8 Recent synthetic methodologies for pyrimidine and its derivatives Farhat IBRAHEEM1,, Furqan Ahmad SADDIQUE1,, Sana ASLAM2,, Asim MANSHA1,, Tahir FAROOQ3,, Matloob AHMAD1;∗, 1Department of Chemistry, Government College University, Faisalabad, Pakistan 2Department of Chemistry, Government College Women University, Faisalabad, Pakistan 3Department of Applied Chemistry, Government College University, Faisalabad, Pakistan Received: 04.06.2018 • Accepted/Published Online: 13.07.2018 • Final Version: 06.12.2018 Abstract: Pyrimidine derivatives are well known due to their remarkable pharmacological potential in various fields of science, and they are also present in some natural substances like DNA and RNA. These scaffolds manifest diversified biological activities such as antimicrobial, antiinflammatory, anti-HIV, antitubercular, antitumor, antineoplastic, and antimalarial. A pyrimidine ring is constructed when chalcones, amidines, guanidine, nitriles, isocyanates, urea, thiourea, and aminopyrazoles undergo condensation, coupling, or cyclization reactions. In this context, the present review illustrates a variety of novel and efficient synthetic approaches towards the synthesis of pyrimidine and its derivatives that were reported recently. Key words: Pyrimidine, synthesis, multicomponent, chalcones, guanidine, urea, thiourea 1. Introduction Pyrimidine 1 is a six-membered heterocyclic compound containing two nitrogen atoms. Its synthetic deriva- tives demonstrate an essential role in modern medicines such as quinazoline alkaloids, which exhibit hypnotic activity. 1 Many simple fused pyrimidines such as purines and pteridines are biologically active. Some have bronchodilatory potential and act as antagonists of the human A 2 A adenosine receptor and constitute some valuable naturally occurring substances such as nucleic acids.
    [Show full text]
  • Vapor Pressures of Pure Substances 2-61
    VAPOR PRESSURES OF PURE SUBSTANCES 2-61 TABLE 2-8 Vapor Pressures of Organic Compounds, up to 1 atm* Pressure, mm Hg Melting Compound 1 5 10 20 40 60 100 200 400 760 point, Name Formula Temperature, °C °C Acenaphthalene C 12 H10 114.8 131.2 148.7 168.2 181.2 197.5 222.1 250.0 277.5 95 Acetal C 6H14 O2 −23.0 −2.3 +8.0 19.6 31.9 39.8 50.1 66.3 84.0 102.2 Acetaldehyde C 2H4O −81.5 −65.1 −56.8 −47.8 −37.8 −31.4 −22.6 −10.0 +4.9 20.2 −123.5 Acetamide C 2H5NO 65.0 92.0 105.0 120.0 135.8 145.8 158.0 178.3 200.0 222.0 81 Acetanilide C 8H9NO 114.0 146.6 162.0 180.0 199.6 211.8 227.2 250.5 277.0 303.8 113.5 Acetic acid C 2H4O2 −17.2 +6.3 17.5 29.9 43.0 51.7 63.0 80.0 99.0 118.1 16.7 anhydride C 4H6O3 1.7 24.8 36.0 48.3 62.1 70.8 82.2 100.0 119.8 139.6 −73 Acetone C 3H6O −59.4 −40.5 −31.1 −20.8 −9.4 −2.0 +7.7 22.7 39.5 56.5 −94.6 Acetonitrile C 2H3N −47.0 −26.6 −16.3 −5.0 +7.7 15.9 27.0 43.7 62.5 81.8 −41 Acetophenone C 8H8O 37.1 64.0 78.0 92.4 109.4 119.8 133.6 154.2 178.0 202.4 20.5 Acetyl chloride C 2H3OCl −50.0 −35.0 −27.6 −19.6 −10.4 −4.5 +3.2 16.1 32.0 50.8 −112.0 Acetylene C 2H2 −142.9 −133.0 −128.2 −122.8 −116.7 −112.8 −107.9 −100.3 −92.0 −84.0 −81.5 Acridine C 13 H9N 129.4 165.8 184.0 203.5 224.2 238.7 256.0 284.0 314.3 346.0 110.5 Acrolein (2-propenal) C 3H4O −64.5 −46.0 −36.7 −26.3 −15.0 −7.5 +2.5 17.5 34.5 52.5 −87.7 Acrylic acid C 3H4O2 +3.5 27.3 39.0 52.0 66.2 75.0 86.1 103.3 122.0 141.0 14 Adipic acid C 6H10 O4 159.5 191.0 205.5 222.0 240.5 251.0 265.0 287.8 312.5 337.5 152 Allene (propadiene) C 3H4 −120.6 −108.0 −101.0 −93.4 −85.2
    [Show full text]