WIIINIPEG, I{ANI1.Oba October 1971

Total Page:16

File Type:pdf, Size:1020Kb

WIIINIPEG, I{ANI1.Oba October 1971 THE UNTVERSITY OF FJAI,TTTOBA STTIDIES ON TSOTHTÁ.ZOIIU}.I SÂLTS AND REIATED CO},IPOUI{DS by GART ED}¡ARD BACIIERS A T}MSIS SIMÌ,1TTTED TO TI{E FACULTY OF GR]I.DUÀTE STIIDIES ÏN PIIRÎI/iL FULIi'TIJ'&Til'r OF TI# REQUTREI.Tiü{TS TÇR TI.III DEGREE I'IÂSTER 0F SCIEÎIICE DEPARTI'ÎE]VT 0F CI{EI,IISTRY WIIINIPEG, I{ANI1.oBA October 1971 üF fi "*i¡l,''ÉËR$$iY LT BRARY ACIOTOIILEDGH,ÍTÍüTS : The research degcribed in thís thesis has been undertaken at tho suggestion of Dr. D. Id. McKínnon, for v¡hose guidance, advice, æd ass*stance ï exprees r¡\y sincere appreciation" My gratitud.e ie also due the National Research CounciÌ of Canada for the scholarships provid.ed. d.uring the course of this research, and the University of }ianitoba for the provisíon of laboratory facilities. Finally, I should like to thank rny colleaguee, I'fiss Sheena Loosmore, Ivlr. Joe Buchsbriber, Iilr. Pat Ma, a¡rd. Mr. Jack Wong. Their forbearance during several unusually od.or-ous experiments was admirable. 11 TA3I,E 0F.coNTlNTS ABSTRACT.......... o.. ó..... o. ...:. r. o õ i.. o.... o.......iii INTRODUCTION Ggngial.. - - . ô. :.' ..... o. ... .. .. .. .. r. .. o. .. .... 1 fsothiazoles. o r . c o. o . ... .. o. ¡. 2 ' I s o thi azo 1 um s s i al t . c . o . c . , . , . , o . ! 4-rsothiazoline-3-thiones... o... ô........ o.... r........ 13 . 3-Isothiazoline-l-thiones....o.....,r........er........18 Thiothiophthenes and an aza arialogue.. o...... c o. o... .,.19 DISCUSSION Purpose of resgarch...... c.. o...^... r.............. o., o..2J Reaction of isothiazolium salts ç¡ittr sutf:p¡ ¡ o o. c . .. .24 Ðirect approaches to 3-thioacylmetirylene isothiazoles. .{l concIusions...... ........... o. ........ .. ..... o..... ....49 EXPERII'TENTAL Ggngrall ¡ ¡ ¡ o........... o... .. e... r.,.... o...... ...51 starting materials...'.............oc........... .....,.52 Isothiazolium salts/sulfur/pyríd.ine Reactions, r . .., .. j9 Attempted d-irect syntheses...... .. o.. o.. e... ,.... .6, Approach to 2rd-diphenylisothiazolium perchlorate....,.TO RE'FERENOES. '.. '............... Ò o r. r...........,..,.... ....,.74 SPEOTRA... ... o... r. r....... o r o .. ... ....... ............8c t 11 ABSTIACT: The reactions of various isothiazolium salt.s with sulfur in refluxing pyrid.ine have been stud.ied. to d.etermine the prod.ucts and. mechanistic pathways involved. ln the course of these investigations, three pre- viously unreported. isothiazolium salts and. a ner.r l-isothiazotine*!- thione have been synthesized. Various approaches to 3-thioacylmethylene isothrazoles a:ed l-acylmetþ- lene isoxazoles have been investigated.. Hor*ever, ring d.econposition has so far prevented the synthesis of such a:ia.logues to the thiothioph- thene system by these synthetic routes A potentially useful approach to 3-unsubstituted-3-isothiazoline-)- thiones has been investigated and should. prove cond.ucive to the synthesis of these compound-s. INTRODUCTTON ï . GÐ{ERAL ÅNTROpUCTION : This thesis concerns s¡rnthetic routes to a number of compounds con- taining the isothiazole nucleuÊ v¡hich were required for severaÌ studies being undertaken in this laboratory. Such compound.s t+ould be usefuÌ in tbe investigation of lrl-dipolar reactionsr oxidation reactioner æd in the eynthesis of 3-thioacyl.nretl¡rlene Ísothiazoles, which are azã analoguee of the thiothiophthenes. These stud.íes willr whore appropriate, be mentioned in a later section. II" ISOTHÏAZOLES: d--P-esç rlp-tÈp n g{_!h q--}!-q r-ess}-e. : Isothiazoleo Ia, is a five-membered. heterocyclic molecule containing adjacent nitrogen and. sulfur atoms. A number of resonance forms may be drawn for the isothiazole molecute (ta - Ij), both requiring s-N +s-N- +s-N $o-Ö.ÇÇ.öööl)ö.+ Ia Tb Ic ïd Ie If Ig Ih Ii ïj (ff - f¡) and not requiríng (fa - fe) the partícipation of sulfur d--orbitale, Both iscthiazol.e and thiazo-1.e, TI, are chemically and physically simi-lar to pyridineo ïïï, s-r 2\' I \ f il uupportins the Longuet*Higgins theory \/* \*"/ of isoeteriu*1 rvhich claims that in II IïI an aromatic systemo the group -CH=CH- is electronically similar to the for- mally bivalent -S-. Taking into account the participation of sulfur d-orbitals, the repì.acement of =S= for =CIí-CH= is also possible. b):lyn th e sSe_g!fl IgoJI) ig¿,o l_çe : The first method of preparing isothiazol-e, described by Adams Slack2t3 involved the oxidation of !-arninobenz[d]isothiazole: Kt'1no¿" ]T[) :"..Ð =*tQ,, -" Û Although both benz[c]isothiazo]es and benz[d]isothiazoles with ben- zene rings containing an arnino group can thus be converted. to isothia- zoles, tho preparations are ted.ious and unsuitable for general synthe- ses, l\n improved reaction3 involves the cyclization of p-iminothio- butyramide v¡ith chlorine or þydrogen peroxrde: HrH¡V¡,¡e This reaction has been extended by Goerdeler4t5'6 to varíous substi- tuted. )-aminoisothiazoles. In a similar reaction, variously subetitu- ted. thioketones afford J-hyd.ro4ye 3-methoxy, and 3-arninoisothiauol""T, ¡ = 0H, Oldo, or ldH, Ph\,Åx An efficient synthetic method for isothiazoles has been developed by Hübenett a¡rdcowork"t*8, involving the catalytic reaction of sulfur dioxide, arnmonia, and an olefin. Thus, from propylene, isothiazolo may be obtained in good. yield. The catalys'b in this case is activated 4 3cl{¿*c}-lcH3 +4S0¿+ 3ruH, 3 * SHao + H¿s -----Þ Çi arumina. simirarryr 4-phenyl-isoihiazole can be synthesized. from a-metþlstyrene, and 4-rnetÌ:ylisothi azore from isobutyrene. The stabílity of the isothiazole ring is evidenced. by the use of reac- tion temperatures in the 200oC to loCo0 "rngu.g Isothiazoles have been obtained. from the reaction of 1,2-dithiolir¡.m salts with anmonía in etha¡roI10 or with.a¡nmoniurn acetate in acetic acid-11. Th" postulated mechanism proceed.s via nucleophilic attack at carbon atom 3 or l: -:þ-,,"*. s-s s-N -\,klq *, *V*' W* R, The utilization of aciùic nret\rne groups to prod.uce isothiazoles is illustrated by the formation of metþl 3-metþt-d-isothiazole carbory- late from thiophosgene and- mettryl p-anrinocrotonâte in absolute etþ1 ether r+ith trietl¡rlamine as cataly"trl2 *\ /NH.. .c:G. + \an, ,:{" ry* u3co2c/ v.*, co2cFl3 .4. second. use of an acidic metþne group was shown by l{ille and co- rho found. that the ad.dition product of acetylenÍc carbonyl "ork*rs13 compounds wÍth sodium thiosulfate would. cyclize in liquid- amrnonia to yield isothiazoles: o NHa S NaO, S-S-CH:Cf+ ë n \,Å.-¡$ However, the instability of the intermediate cis-thiocyanate aclduct regults in low yield.s. Nevertheless, the reaction is of value since it ca¡r be ad-ap'eecl to the s¡rnthesis of isose}"n"rolu".14 The cyclization of d.icyanoet$rlened"ithiolate to give an isothiazole vuas d.emonstrated, by Soed.erbaeckl5 tnd. Hatchardl6: NC, SNa s s-N rucf\stuo tras\./snr, CN A similar reaction has recently been reported by llakagav.'a et al17 *ho found that benzylid.enemalononitriles v¡ouId react v¡ith sulfur chlorícles or thio4yÌ chloride in pyridine to give an isothiazole by an as-yet unelucidated- mechani sm: s¿cl¿ sctz s_N A**cFl:c'€ \ or SOCl¿ /Pyr n'\.n" CN A nurnber of other isothiazole syntheses have been based on the active nucleophiì-ic methylene groups as found in malononitrile or phenylaceto- nitrile' these are generatly used. to form intermed.iates in the presence of base, v¡hich on treatr¡ent rrith sulfur yield. isothiaøole,s, Di(triethyl- eunnonio)rnetþlenenralononitrile lras formea in the reaction of acetoni- trile rvith rnalononitrile in trietþlaraine/carbon disutfid.e. Oxidation with sulfur in methenol followed. by treatment vrith methyl iod.id.e af- 1 B forded 3, 5-di( thiomethyl) -d-c;,¿noisothiazolu, pN etrÑs l'.4eCN l.l^C + t", ,sÑur. 1. S/r¡eol l-ir¡ t'ct+ Eñ* NC c MesVsr'1e CN {¡Cyano-l-amino-1, 2-d-ithiole-3-thione, obtained from malononitril-e, sulfurr and carbon disulfíd.e in the presonce of triettrylanine, under- went ring-opening and S-S bond. scission on treatment with potassium þdroxide. fsomerization and. ring-closure yielded dipotassiun-3 r4- dithio-4-cyanoisothiazole, which on methylation gave 1,5-di( thiomethyl)- 1 4-cya¡roi sothi azo le 9 : EbtN n-tru (tn + csr o s - Î-Ì Koll Þ î-il ttu¿soa- -u.*Ys-o*t\r/'--î.r$.*, Sod"ium viqyl srrlfidee, obtained by thioaoylatÍng malononitrile with esters of d.ithiocarbovlicr thionocarborylic, trithionocarborylic, or xanthic acid.s in anhydroìs ethanol with soclium ethoxid.e as catalyst, rqhen treated. with chloramine yieldecl 3-amino-4-cyanoisothiazotes20: ,cN Mes.. Naogb, N ca_75Na H.cr + NHaCI , CN Þ'^/rcR ff-- N.F.\RFIC' .R E¿o,¡¿v -* *\rÅ*n, CN Cyanothioacetamide, produced from the reaction of þd"rogen sulfide and malononitrile, reacts v¡ith carbon d.isulfid.e in the presence of a sodium alkoxide to give, on metÏ¡rlation, an intermediate which can be oxidized with iodine in ethanol to yield 3,5-di(thiomethyf)-+- cyanoisothiazole2l ¡ S il ,CN ¡. CS*/NaoEb õ s + H¿S NCeHaChlHe Ñu, T- Hrco -+ CN -N Dithioic acid. sal-ts, produced by treating phenylacetonitrile r.¡ith carbon disulfÍd.e in the presence of sod.ium þdrid.e and dimetþyì-for- mamide, can be cyclized r.rith eulfur in ethanol, Acidification yields 22: {-pheny}i sothiazo Ie-l , !-d i thiol s_N PhcH?cht +cs¿ lrflL' fi iìi rslELoFr u*-*rrvl m* usVsH Ph The oxiclative cyclization of p-mercaptopropionitrile with halogen B to yield, 3-haloisothiazoles23 in,rollres the lose of three proions by a mechanism which, as yet, is unclearS xu o X=CIorBr u, =Çï- 'p -iminoketones, such as p-imino-p-moz'pholinoetþI phenyl ketone, may be sulfurized- with sulfur and.
Recommended publications
  • Unit One Part 2: Naming and Functional Groups
    gjr-–- 1 Unit One Part 2: naming and functional groups • To write and interpret IUPAC names for small, simple molecules • Identify some common functional groups found in organic molecules O CH3 H3C N H N O N N O H3C S N O N H3C viagra™ (trade name) sildenafil (trivial name) 5-(2-ethoxy-5-(4-methylpiperazin-1-ylsulfonyl)phenyl)-1-methyl-3-propyl-1H- pyrazolo[4,3-d] pyrimidin-7(6H)-one dr gareth rowlands; [email protected]; science tower a4.12 http://www.massey.ac.nz/~gjrowlan gjr-–- 2 Systematic (IUPAC) naming PREFIX PARENT SUFFIX substituents / minor number of C principal functional functional groups AND multiple bond group index • Comprises of three main parts • Note: multiple bond index is always incorporated in parent section No. Carbons Root No. Carbons Root Multiple-bond 1 meth 6 hex Bond index 2 eth 7 hept C–C an(e) 3 prop 8 oct C=C en(e) 4 but 9 non C≡C yn(e) 5 pent 10 dec gjr-–- 3 Systematic (IUPAC) naming: functional groups Functional group Structure Suffix Prefix General form O –oic acid acid –carboxylic acid carboxy R-COOH R OH O O –oic anhydride anhydride –carboxylic anhydride R-C(O)OC(O)-R R O R O –oyl chloride acyl chloride -carbonyl chloride chlorocarbonyl R-COCl R Cl O –oate ester –carboxylate alkoxycarbonyl R-COOR R OR O –amide amide –carboxamide carbamoyl R-CONH2 R NH2 nitrile R N –nitrile cyano R-C≡N O –al aldehyde –carbaldehyde oxo R-CHO R H O ketone –one oxo R-CO-R R R alcohol R OH –ol hydroxy R-OH amine R NH2 –amine amino R-NH2 O ether R R –ether alkoxy R-O-R alkyl bromide bromo R-Br (alkyl halide) R Br (halo) (R-X) gjr-–- 4 Nomenclature rules 1.
    [Show full text]
  • Polymeric Reagents with Propane-1,3-Dithiol Functions and Their Precursors for Supported Organic Syntheses
    J. Org. Chem. 2000, 65, 4839-4842 4839 Polymeric Reagents with Propane-1,3-dithiol Functions and Their Precursors for Supported Organic Syntheses Vincenzo Bertini,*,† Francesco Lucchesini,† Marco Pocci,† and Angela De Munno‡ Dipartimento di Chimica e Tecnologie Farmaceutiche ed Alimentari, Universita´ di Genova, Via Brigata Salerno, I-16147 Genova, Italy, and Dipartimento di Chimica e Chimica Industriale, Universita´ di Pisa, Via Risorgimento, 35, I-56126 Pisa, Italy [email protected] Received January 19, 2000 Reliable completely odorless syntheses of soluble copolymeric reagents of styrene type containing propane-1,3-dithiol functions able to convert carbonyl compounds into 1,3-dithiane derivatives and to support other useful transformations are reported together with their progenitor copolymers containing benzenesulfonate or thioacetate groups perfectly stable in open air and suitable for unlimited storage. The effectiveness of the prepared reagents as tools for polymer-supported syntheses to produce ketones by aldehyde umpolung and alkylation is tested in the conversion of benzaldehyde to phenyl n-hexyl ketone starting from copolymers with different contents of active units and molecular weights. To facilitate the adaptation of the prepared soluble copolymeric reagents to other possible applications, a table of solvents and nonsolvents is presented. Introduction Scheme 1 Recently we have reported in a preliminary com- munication1 how to harness the great synthetic potenti- alities of thioacetals and thioketals by preparing, with a completely odorless synthesis, polymeric reagents2,3 of styrene type containing propane-1,3-dithiol functions effective in producing ketones by aldehyde umpolung and alkylation after the formation of 1,3-dithiane derivatives. Such polymeric reagents were obtained through a pro- cedure based on the use of the difunctional monomer 1 prepared from commercial 4-vinylbenzyl chloride (Scheme 1), its copolymerization with styrene, and chemical modification of its copolymers.
    [Show full text]
  • Identification of a Common Chemical Signal Regulating the Induction Of
    Proc. Nati. Acad. Sci. USA Vol. 85, pp. 8261-8265, November 1988 Medical Sciences Identification of a common chemical signal regulating the induction of enzymes that protect against chemical carcinogenesis (Michael acceptors/quinone reductase/glutathione S-transferase/anticarcinogens) PAUL TALALAY, MARY J. DE LONG, AND HANS J. PROCHASKA Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 Contributed by Paul Talalay, July 19, 1988 ABSTRACT Carcinogenesis is blocked by an extraordi- al inducers act are less clear (3). This paper extends our nary variety of agents belonging to many different classes- earlier efforts to identify structural features important for e.g., phenolic antioxidants, azo dyes, polycyclic aromatics, phase II enzyme induction by diphenols and phenylenedia- flavonoids, coumarins, cinnamates, indoles, isothiocyanates, mines (5). Since the specific activity of QR in the Hepa lclc7 1,2-dithiol-3-thiones, and thiocarbamates. The only known murine hepatoma cells is raised by virtually all compounds common property of these anticarcinogens is their ability to that produce coordinate elevations of phase II enzymes in elevate in animal cells the activities of enzymes that inactivate vivo (4, 5, 7), this system was used to determine the potency the reactive electrophilic forms of carcinogens. Structure- of various types of enzyme inducers. Some inducers identi- activity studies on the induction of quinone reductase fied in cell culture were also tested as inducers
    [Show full text]
  • 514636-Unified-Chemistry.Pdf
    Qualification Accredited A LEVEL Exemplar Candidate Work CHEMISTRY A H432 For first teaching in 2015 H432/03 Summer 2017 examination series Version 1 www.ocr.org.uk/chemistry A Level Chemistry A Exemplar Candidate Work Contents Introduction 3 Question 3(b) 20 Commentary 21 Question 1(a) 4 Commentary 4 Question 3(c)(i) 22 Commentary 22 Question 1(b) 5 Commentary 5 Question 3(c)(ii) 23 Commentary 24 Question 1(c) 6 Commentary 6 Question 4(a)(i) 25 Commentary 26 Question 1(d) 7 Commentary 7 Question 4(a)(ii) 27 Commentary 28 Question 1(e) 8 Commentary 8 Question 4(b)(i) 29 Commentary 29 Question 2(a) 9 Commentary 11 Question 4(b)(ii) 30 Commentary 30 Question 2(b) 12 Commentary 12 Question 4(c)(i) 31 Commentary 31 Question 2(c) 13 Commentary 13 Question 4(c)(ii) 32 Commentary 32 Question 2(d)(i) 14 Commenary 14 Question 5(a)(i) 33 Commentary 33 Question 2(d)(ii) 15 Commentary 15 Question 5(a)(ii) 34 Commentary 34 Question 2(d)(iii) 16 Commentary 16 Question 5(a)(iii) 35 Commentary 35 Question 3(a)(i) 17 Commentary 18 Question 5(a)(iv) 36 Commentary 36 Question 3(a)(ii) 19 Commentary 19 Question 5(b) 37 Commentary 38 2 © OCR 2017 A Level Chemistry A Exemplar Candidate Work Introduction These exemplar answers have been chosen from the summer 2017 examination series. OCR is open to a wide variety of approaches and all answers are considered on their merits. These exemplars, therefore, should not be seen as the only way to answer questions but do illustrate how the mark scheme has been applied.
    [Show full text]
  • Acetalization of Carbonyl Compounds, and Desilylation of Tert-Butyldimethylsilyl Ethers
    NEW SYNTHETIC METHODOLOGIES FOR THIO- AND DETHIO- ACETALIZATION OF CARBONYL COMPOUNDS, AND DESILYLATION OF TERT-BUTYLDIMETHYLSILYL ETHERS A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY by EJABUL MONDAL to the DEPARTMENT OF CHEMISTRY INDIAN INSTITUTE OF TECHNOLOGY GUWAHATI North Guwahati, Guwahati -781 039 April, 2004 Dedicated to my late father TH-146_01612206 DEPARTMENT OF CHEMISTRY INDIAN INSTITUTE OF TECHNOLOGY, GUWAHATI INDIA CERTIFICATE-I This is to certify that Mr. Ejabul Mondal has satisfactorily completed all the courses required for the Ph. D. degree programme. These courses include: CH 603 Supra Molecules: Concept and Applications CH 611 Bio Inorganic Chemistry CH 627 New Reagents in Organic Synthesis CH 630 A Molecular Approach to Physical Chemistry Mr. Ejabul Mondal successfully completed his Ph. D. qualifying examination in May 8, 2003. (Dr. Jubaraj B. Baruah) Dr. Anil K. Saikia Head Secretary Department of Chemistry Departmental Post Graduate Committee I. I. T. Guwahati Department of Chemistry I. I. T. Guwahati TH-146_01612206 Indian Institute of Technology, Guwahati North Guwahati, Guwahati, 781 039, India Tel. No.: 0091-361-26902305 Fax No.: 0091-361-2690762 E. mail: [email protected] [email protected] Dr. Abu T. Khan Professor, Department of Chemistry ___________________________________________________________________________ CERTIFICATE – II Date: April , 2004 This is to certify that Mr. Ejabul Mondal has been working in my research group since March 30, 1999. At the beginning, he joined as a Junior Research Fellow in the CSIR project and later on, he has been registered as a self-sponsored Ph. D student on January 4, 2002 in the Department of Chemistry.
    [Show full text]
  • University of Illinois
    UNIVERSITY OF ILLINOIS THIS IS TO CERTIFY THAT THE THESIS PREPARED UNDER MY SUPERVISION BY ..... M < c h C IS ENTITLED............. .................................CMAcj C . ' Z o + i 'c , ... £ f ... t r j -Cs-H * £ § ± IIU l_ U <)J3$U IS APPROVED BY ME AS FULFILLING THIS PART OF THE REQUIREMENTS FOR THE DEGREE OF.............£>?.£h.«(®.£ ......... .................................. Ol*4 SYNTHESIS AND CHARACTERISATION OF (f|-C5Me4Et)Ru(CO)?SH BY NANCY ELLEN NICHOLS THESIS for the DECREE OF BACHELOR OF SCIENCE IN CHEMISTRY College of Liberal Arte end Soienoea University of Illinois Urbanei Illinois 1986 % V TABLE OF CONTENTS I* Introduction ........... References ........... 9 H . Chapter 1: Synthesis of (iJ-Cj^EtjRuf C0)?3H 8 Results 9 Disoussion ...... .. 11 Experimental 14 References 17 Tables iQ Figures .......... 1 1 1 . Chapter ?t Reactions of (i^-Cji^EtjRufCO^SH .......,...2 5 Results ##26 Disoussion 32 Experimental 34 References 37 Tables 39 Figures 40 INTRODUCTION Hydrodesulfurisation (HDS) is an important catalytic procaas used in tha purification of patrolaum products. [1,2] This procsss involves tha hydroganolysis of organosulfur compounds ss shown in tha equations below. [3] RSH + Ha— _ » RH + HaS RSR + 2 Hg---- » 2RH ♦ Ha 8 R88R + 3Ha— *2RH + 2Ha& Interestingly, it has been found that the types of compounds which have high HDS activity are transition metal sulfides. In addition, measurements of the catalytic activity of a series of transition metal sulfides have shown that the ability of a particular sulfide to catalyse the HOB reaction is related to the position of the transition metal in the periodic table. [4] In particular, studies indicate that first row transition metal sulfides are relatively inactive, while the seoond and third row transition metals show maximum activity with ruthenium and osmium.
    [Show full text]
  • The Efficiency of Enzymatic L-Cysteine Oxidation in Mammalian Systems Derives from the Optimal Organization of the Active Site of Cysteine Dioxygenase
    The Efficiency of Enzymatic L-Cysteine Oxidation in Mammalian Systems Derives from the Optimal Organization of the Active Site of Cysteine Dioxygenase by Catherine Wangui Njeri A dissertation submitted to the Graduate Faculty of Auburn University in partial fulfillment of the requirements for the Degree of Doctor of Philosophy Auburn, Alabama May 4, 2014 Copyright 2014 by Catherine Wangui Njeri Approved by Holly R. Ellis, Chair, Associate Professor of Chemistry and Biochemistry Douglas C. Goodwin, Associate professor of Chemistry and Biochemistry Evert E. Duin, Associate Professor of Chemistry and Biochemistry Paul A. Cobine, Assistant Professor of Biological Sciences Benson T. Akingbemi, Associate Professor of Anatomy Abstract Intracellular concentrations of free cysteine in mammalian organisms are maintained within a healthy equilibrium by the mononuclear iron-dependent enzyme, cysteine dioxygenase (CDO). CDO catalyzes the oxidation of L-cysteine to L-cysteine sulfinic acid (L-CSA), by incorporating both atoms of molecular oxygen into the thiol group of L-cysteine. The product of this reaction, L-cysteine sulfinic acid, lies at a metabolic branch-point that leads to the formation of pyruvate and sulfate or taurine. The available three-dimensional structures of CDO have revealed the presence of two very interesting features within the active site (1-3). First, in close proximity to the active site iron, is a covalent crosslink between Cys93 and Tyr157. The functions of this structure and the factors that lead to its biogenesis in CDO have been a subject of vigorous investigation. Purified recombinant CDO exists as a mixture of the crosslinked and non crosslinked isoforms, and previous studies of CDO have involved a heterogenous mixture of the two.
    [Show full text]
  • Oral Chelation Therapy for Patients with Lead Poisoning
    ORAL CHELATION THERAPY FOR PATIENTS WITH LEAD POISONING Jennifer A. Lowry, MD Division of Clinical Pharmacology and Medical Toxicology The Children’s Mercy Hospitals and Clinics Kansas City, MO 64108 Tel: (816) 234-3059 Fax: (816) 855-1958 December 2010 1 TABLE OF CONTENTS 1. Background of Lead Poisoning …………………………………………………………...3 a. Clinical Significance of Lead Measurements …………………………………….3 b. Absorption of Lead and Its Internal Distribution Within the Body ………………3 c. Toxic Effects of Exposure to Lead in Children and Adults ………………………4 d. Reproductive and Developmental Effects………………………………………...5 e. Mechanisms of Lead Toxicity ……………………………………………………6 f. Concentration of Lead in Blood Deemed Safe for Children/Adults………………6 g. Use of Blood Lead Measurements as a Marker of Lead Exposure ……………….7 2. Management of the Child with Elevated Blood Lead Concentrations …………………...8 a. Decreasing Exposure……………………………………………………………...8 b. Chelation Therapy…………………………………………………………………8 3. Oral Chelation Therapy …………………………………………………………………...8 a. Meso-2,3 dimercaptosuccinic acid (DMSA, Succimer) …………………………8 i. Pharmacokinetics………………………………………………………….9 ii. Dosing …………………………………………………………………….9 iii. Efficacy……………………………………………………………………9 iv. Safety…………………………………………………………………….11 b. Racemic-2,3-dimercapto-1-propanesulfonic acid (DMPS, Unithiol)……………11 i. Pharmacokinetics………………………………………………………...12 ii. Dosing ……………………………………………………………………12 iii. Efficacy…………………………………………………………………..12 iv. Safety…………………………………………………………………….12 c. Penicillamine……………………………………………………………………..12 i. Pharmacokinetics………………………………………………………...13
    [Show full text]
  • Conversion of Diols to Dithiols Via a Dehydration Polycondensation with a Dicarboxylic Acid Containing a Disulfide and Subsequent Reduction
    Polymer Journal (2010) 42, 956–959 & The Society of Polymer Science, Japan (SPSJ) All rights reserved 0032-3896/10 $32.00 www.nature.com/pj RAPID COMMUNICATION Conversion of diols to dithiols via a dehydration polycondensation with a dicarboxylic acid containing a disulfide and subsequent reduction Polymer Journal (2010) 42, 956–959; doi:10.1038/pj.2010.100; published online 27 October 2010 Derivatization of compounds often trans- thiol-ene and thiol-yne click reactions11–13 nesulfonate catalysts that afforded aliphatic forms the targeted functional group; however, have been useful. Application of thiol-related polyesters with number-average-molecular 4 most of these processes require severe reac- chemistry to polymer synthesis promises to weights (Mns) 41.0Â10 (refs 16–24). This tion conditions and/or excessive amounts of open a new frontier in material design, but polycondensation system made it possible to reagents.1 These drawbacks frequently occur first, methods that readily afford a thiol on use thermally unstable monomers that con- when transformations of polymer termini are deprotection must be developed. Martinelle tained a carbon–carbon double bond,17 a attempted. If we could derivatize the terminal and co-workers14 described a one-step end- bromine substituent18 and/or a hydroxyl functional groups of polymers easily, we functionalization of poly(e-caprolactone) by substituent.21,23 could design new types of polymers with a ring-opening polymerization that was cat- The aforementioned studies, including our predetermined properties. Transformations alyzed by Candida antarctica lipase B and own, prompted us to investigate the possibi- of polymer termini have been reported by used mercaptoethanol as the initiator.
    [Show full text]
  • The Use of Aerobic Aldehyde C-H Activation for the Construction of C-C and C-N Bonds
    University College London The use of aerobic aldehyde C-H activation for the construction of C-C and C-N bonds By Vijay Chudasama Submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy Declaration I, Vijay Chudasama, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Vijay Chudasama August 2011 i Abstract This thesis describes a series of studies directed towards the use of aerobic aldehyde C-H activation for the construction of C-C and C-N bonds by the process of hydroacylation. Chapter 1 provides an introduction to the research project and an overview of strategies for hydroacylation. Chapter 2 describes the application of aerobic aldehyde C-H activation for the hydroacylation of vinyl sulfonates and sulfones. A discussion on the mechanism of the transformation, the effect of using aldehydes with different oxidation profiles and the application of chiral aldehydes is also included. Chapter 3 describes the functionalisation of -keto sulfonates with particular emphasis on an elimination/conjugate addition strategy, which provides an indirect approach to the hydroacylation of electron rich alkenes. Chapters 4 and 5 describe the application of aerobic aldehyde C-H activation towards the hydroacylation of α,-unsaturated esters and vinyl phosphonates, respectively. An in-depth discussion on the mechanism and aldehyde tolerance of each transformation is also included. Chapter 6 describes acyl radical approaches towards C-N bond formation with particular emphasis on the synthesis of amides and acyl hydrazides.
    [Show full text]
  • (Bdeth2) and Its Metal Compounds
    University of Kentucky UKnowledge University of Kentucky Doctoral Dissertations Graduate School 2008 BENZENE-1,3-DIAMIDOETHANETHIOL (BDETH2) AND ITS METAL COMPOUNDS Kamruz Md Zaman University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Zaman, Kamruz Md, "BENZENE-1,3-DIAMIDOETHANETHIOL (BDETH2) AND ITS METAL COMPOUNDS" (2008). University of Kentucky Doctoral Dissertations. 644. https://uknowledge.uky.edu/gradschool_diss/644 This Dissertation is brought to you for free and open access by the Graduate School at UKnowledge. It has been accepted for inclusion in University of Kentucky Doctoral Dissertations by an authorized administrator of UKnowledge. For more information, please contact [email protected]. ABSTRACT OF DISSERTATION Kamruz Md Zaman The Graduate School University of Kentucky 2008 BENZENE-1,3-DIAMIDOETHANETHIOL (BDETH2) AND ITS METAL COMPOUNDS _____________________________ ABSTRACT OF DISSERTATION _____________________________ A dissertation submitted in partial fulfillment of the requirement for the degree of Doctor of Philosophy in the College of Arts and Science at the University of Kentucky By Kamruz Md Zaman Lexington, Kentucky Director: Dr. David A. Atwood, Professor of Chemistry Lexington, Kentucky 2008 Copyright © Kamruz Md Zaman 2008 ABSTRACT OF DISSERTATION BENZENE-1,3-DIAMIDOETHANETHIOL (BDETH2) AND ITS METAL COMPOUNDS There is a global need to find a permanent and readily implemented solution to the problem of heavy metal pollution in aqueous environments. A dithiol compound, benzene-1,3-diamidoethanethiol (BDETH2), also known as N,N'-bis(2-mercaptoethyl) isophthalamide or N,N'-bis(2-mercaptoethyl)-1,3-benzenedicarboxamide, capable of binding divalent metal ions, has been synthesized and characterized.
    [Show full text]
  • Structure-Reactivity Relations for Thiol-Disulfide Interchange Janette Houk and George M
    J. Am. Chem. SOC.1987, 109, 6825-6836 6825 ‘H NMR (22 OC, benzene-d6): 6 3.26 (s, OSCMe), 3.03 (s, 2JwH= A systematic search of a limited hemisphere of reciprocal space lo- 8.54 Hz, CH2CMe3next to S), 2.85 (s, ’JWH= 9.98 Hz, CH2CMe3next cated a set of diffraction maxima with systematic absences corresponding to Oh 2.32 (s. O,CMe), 2.26 (s,.- 0,CMe trans to OSCMe) 1.49, 1.46 (s, to the unique monoclinic space group P2,/a. Subsequent solution and CH2CMe3): refinement confirmed this choice. IR: 324 (m), 333 (m), 375 (w), 450 (w), 620 (w), 627 (w), 668 (ms), The structure was solved by a combination of direct methods 680 (m). 907 (mw), 932 (w). 1018 (w), 1040 (w), 1088 (vs), 1175 (ms), (MULTAN~S)and Fourier techniques and refined by full-matrix least 1202(mw), 1236 (ms), 1349 (m), 1361 (ms), 1374 (ms), 1438 (vs), 1460 squares. Many of the hydrogen atom positions were visible in a difference (s), 1492 (m) cm-I. Fourier phased on the non-hydrogen parameters. The positions of all W2(np)2(02CNMe2)4.In a Schlenk flask W2(np)2(NMe2)4(0.30 g, hydrogens were calculated and placed in fixed idealized positions (d(C- 0.44 mmol) was dissolved in CH2C12and then frozen in liquid N,. A H) = 0.95 A) for the final cycles. The hydrogen atoms were assigned large excess (>4 equiv) of C02was condensed into the flask. The so- a thermal parameter of 1 + Bise of the carbon atom to which they were lution was then slowly warmed to room temperature while the flask was bound.
    [Show full text]