Synthetic Routes Towards Thiazolo[1,3,5]Triazines (Review)1
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Methylenediphenyl Diisocyanate and O-(P-Isocyanatobenzyl)Phenyl Isocyanate / Methylene Diphenyl Diisocyanate EC No 905-806-4
Substance Evaluation Conclusion document EC No 905-806-4 SUBSTANCE EVALUATION CONCLUSION as required by REACH Article 48 and EVALUATION REPORT for Reaction mass of 4,4'-methylenediphenyl diisocyanate and o-(p-isocyanatobenzyl)phenyl isocyanate / methylene diphenyl diisocyanate EC No 905-806-4 CAS No N/A Evaluating Member State(s): Estonia Dated: 13 July 2019 Substance Evaluation Conclusion document EC No 905-806-4 Evaluating Member State Competent Authority Health Board Paldiski maantee 81 10167 Tallinn Estonia Tel: +3727943500 Fax: N/A Email: [email protected] Year of evaluation in CoRAP: 2015 Before concluding the substance evaluation a Decision to request further information was issued on: 23 February 2017. Further information on registered substances here: http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances Estonia Page 2 of 30 13 July 2019 Substance Evaluation Conclusion document EC No 905-806-4 DISCLAIMER This document has been prepared by the evaluating Member State as a part of the substance evaluation process under the REACH Regulation (EC) No 1907/2006. The information and views set out in this document are those of the author and do not necessarily reflect the position or opinion of the European Chemicals Agency or other Member States. The Agency does not guarantee the accuracy of the information included in the document. Neither the Agency nor the evaluating Member State nor any person acting on either of their behalves may be held liable for the use which may be made of the information contained therein. Statements made or information contained in the document are without prejudice to any further regulatory work that the Agency or Member States may initiate at a later stage. -
1,3,5-Triazine As Core for the Preparation of Dendrons
The Free Internet Journal Paper for Organic Chemistry Archive for Arkivoc 2020, part iii, 0-0 Organic Chemistry to be inserted by editorial office 1,3,5-Triazine as core for the preparation of dendrons Rotimi Sheyi,a Anamika Sharma,a,b Ashish Kumar,a,b Ayman El-Faham,c,d Beatriz G. de la Torre,b,* and Fernando Albericioa,c,e,f* aPeptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South Africa bKwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa cDepartment of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia dDepartment of Chemistry, Faculty of Science, Alexandria University, PO Box 426, Alexandria 21321, Egypt eInstitute for Advanced Chemistry of Catalonia (IQAC-CSIC), 08034 Barcelona, Spain fCIBER-BBN (Networking Centre on Bioengineering, Biomaterials and Nanomedicine) and Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain *Corresponding authors. email: [email protected]; [email protected] Received mm-dd-yyyy Accepted mm-dd-yyyy Published on line mm-dd-yyyy Dates to be inserted by editorial office Abstract A unique property of 2,4,6-trichloro-1,3,5-triazine (TCT) is its ability to undergoes a nucleophilic aromatic substitution reaction (SNAr) under temperature-controlled conditions. Using a convenient and biologically friendly protocol, mono-substituted s-triazines were treated with excess nucleophiles to obtain tri-substituted triazines in 1 + 2 mode (one nucleophile as the first substitution followed by another nucleophile for the other two positions). -
S-Triazine: a Privileged Structure for Drug Discovery and Bioconjugation
molecules Review s-Triazine: A Privileged Structure for Drug Discovery and Bioconjugation Anamika Sharma 1,2 , Rotimi Sheyi 1, Beatriz G. de la Torre 1,2 , Ayman El-Faham 3,4,* and Fernando Albericio 1,3,5,6,* 1 Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South Africa; [email protected] (A.S.); [email protected] (R.S.); [email protected] (B.G.d.l.T.) 2 KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa 3 Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia 4 Chemistry Department, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 12321, Egypt 5 Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), 08034 Barcelona, Spain 6 CIBER-BBN (Networking Centre on Bioengineering, Biomaterials and Nanomedicine) and Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain * Correspondence: [email protected] (A.E.-F.); [email protected] (F.A.) Abstract: This review provides an overview of the broad applicability of s-triazine. Our many years working with this intriguing moiety allow us to discuss its wide activity spectrum (inhibition against MAO-A and -B, anticancer/antiproliferative and antimicrobial activity, antibacterial activity against MDR clinical isolates, antileishmanial agent, and use as drug nano delivery system). Most Citation: Sharma, A.; Sheyi, R.; of the compounds addressed in our studies and those performed by other groups contain only de la Torre, B.G.; El-Faham, A.; N-substitution. -
A Novel Nonphosgene Process for the Synthesis of Methyl Nphenyl
Chinese Journal of Chemistry, 2004.22.782-786 Article A Novel Non-phosgene Process for the Synthesis of Methyl N-Phenyl Carbamate from Methanol and Phenylurea: Effect of Solvent and Catalyst WANG, Xin-Kuia(3/l&S) YAN, Shi-Run'vb(/q@%d) CAO, Yong*(g!F!) FAN, Kang-Nian'pb(3i5@+) HE,He-Yongb(W@B!) KANG, Mao-Qing"(fiit$W) PENG, Shao-Yia(G9B) a Institute of Coal Chemistty Chinese Academy of Sciences, Taiyuan, Shami 030001, China b Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Deparfment of Chemistv, Fudan University, Shanghai 200433. China A novel environmentally benign process for the synthesis of methyl N-phenyl carbamate (Mpc) from methanol and phenylurea was studied. Effect of solvent and catalyst on the reaction behavior was investigated. The IR spectra of methanol and phenylurea dissolved in different solvents were also recorded. Compared with use of methanol as both a reactant and a solvent, phenylurea conversion and selectivity to Mpc increased by using toluene, benzene or anisole as a solvent, while phenylurea conversion decreased slightly by using n-octane as a solvent. The phenylurea conversion declined nearly 50% when dimethyl sulfoxide (DMSO) was used as a reaction media, and MPC selec- tivity decreased as well. The catalytic reaction tests showed that a basic catalyst enhanced the selectivity to Mpc while an acidic catalyst promoted the formation of methyl carbamate and aniline. Moderate degree of basicity showed the best catalyhc performance in the cases studied. Keywords methyl N-phenyl carbamate synthesis, phenylurea, phosgene-free, solvent effect, acid-base catalyst Introduction tion of methanol from DMC azeotrope, and DMC is relatively expensive. -
Tertiary Alkylamines As Nucleophiles in Substitution Reactions At
Molecules 2011, 16, 10013-10028; doi:10.3390/molecules161210013 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Communication Tertiary Alkylamines as Nucleophiles in Substitution Reactions at Heteroaromatic Halide During the Synthesis of the Highly Potent Pirinixic Acid Derivative 2-(4-Chloro-6-(2,3- dimethylphenylamino)pyrimidin-2-ylthio)octanoic Acid (YS-121) Matthias Gabler and Manfred Schubert-Zsilavecz * Goethe-University Frankfurt, Institute of Pharmaceutical Chemistry, Max-von-Laue-Str. 9, D-60438 Frankfurt/M., Germany * Author to whom correspondence should be addressed: E-Mail: [email protected]; Tel.: +49-69-798-29339; Fax: +49-69-798-29332. Received: 18 November 2011 / Accepted: 30 November 2011 / Published: 5 December 2011 Abstract: YS-121 [2-(4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)octanoic acid] is the result of target-oriented structural derivatization of pirinixic acid. It is a potent dual PPARα/γ-agonist, as well as a potent dual 5-LO/mPGES-1-inhibitor. Additionally, recent studies showed an anti-inflammatory efficacy in vivo. Because of its interference with many targets, YS-121 is a promising drug candidate for the treatment of inflammatory diseases. Ongoing preclinical studies will thus necessitate huge amounts of YS-121. To cope with those requirements, we have optimized the synthesis of YS-121. Surprisingly, we isolated and characterized byproducts during the resulting from nucleophilic aromatic substitution reactions by different tertiary alkylamines at a heteroaromatic halide. These amines should actually serve as assisting bases, because of their low nucleophilicity. This astonishing fact was not described in former publications concerning that type of reaction and, therefore, might be useful for further reaction improvement in general. -
1,2,3-Triazine Scaffold As a Potent Biologically Active Moiety: a Mini Review
Send Orders for Reprints to [email protected] 72 Mini-Reviews in Medicinal Chemistry, 2014, 14, 72-83 1,2,3-Triazine Scaffold as a Potent Biologically Active Moiety: A Mini Review Rajeev Kumar1*, Amar Deep Singh1, Jitendra Singh1, Hariram Singh1, R.K. Roy1 and Anurag Chaudhary2 1Dr. K.N. Modi Institute of Pharmaceutical Education and Research, Inside Cotton Mill Compound, Modinagar, Ghaziabad, Pin-201201, U.P., India; 2Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Baghpat Crossing, Meerut Bypass Road, Meerut-250005, India Abstract: 1,2,3-Triazine is an interesting class of heterocyclic compounds. Various synthetic analogs of 1,2,3-triazine have been prepared and evaluated for many pharmacological activities in different models with desired findings. Some analogs have shown potent pharmacological activity and may be considered as lead molecule for the development of future drugs. This review is an attempt to organize the chemical and pharmacological aspects of 1,2,3-triazine analogs reported till date systematically since 1970. Keywords: Anticancer activity, antimicrobial activity, antiprotozoal, in vivo, 1,2,3-triazine. INTRODUCTION which have significant pharmacological activities. Tubercidin inhibits the growth of several strains of bacteria. Tubercidin Triazines are six membered ring compounds containing and its 5-substituted derivatives inhibit both DNA and RNA three nitrogen atoms. Depending on the position of the viruses at the concentrations that inhibit DNA, RNA and nitrogen atom, three different triazine systems namely, 1,3,5- protein synthesis in mice and human cell lines. Toyocamycin triazine (s-triazine, 1), 1,2,4-triazine (2) and 1,2,3-triazine (3) is a known antineoplastic antibiotic with specific antitumor are possible. -
TRIAZINE HERBICIDES and THEIR METABOLITES in URINE 8315
TRIAZINE HERBICIDES and THEIR METABOLITES in URINE 8315 FORMULAS: Table 1 MW: Table 1 CAS: Table 1 RTECS: Table 1 METHOD: 8315, Issue 1 EVALUATION: PARTIAL Issue 1: 15 March 2003 BIOLOGICAL INDICATOR OF: Exposure to triazine herbicides (1) - (4). SYNONYMS: See TABLE 1 SAMPLING MEASUREMENT SPECIMEN: Urine TECHNIQUE: GAS CHROMATOGRAPHY, MASS SELECTIVE DETECTOR VOLUME: At least 15 mL of sample ANALYTE: s-Triazines (1) - (6) PRESERVATIVE: None EXTRACTION: Two liquid/liquid steps SHIPMENT: Frozen INJECTION SAMPLE VOLUME: 1 :L STABILITY: Not established. Appear to be quite stable frozen for long (> one year) TEMPERATURE periods of time -INJECTION: 280 °C -DETECTOR: 285 °C CONTROLS: Urine from non-exposed persons. -COLUMN: 50 °C hold for one minute, 50°C/min to 160 °C, 3.5 °C/min to 230 °C, 50°C/min to 280 °C, hold 2 minutes. Total run time, 26.20 min Solvent delay- 5.5 min ELECTRON MULTIPLIER VOLTAGE: +153 mV from tune setting CARRIER GAS: Helium, 1.5 mL/min COLUMN: Capillary, fused silica, 30 m x 0.20-mm ID; 0.20 :m film SPB-5 or equivalent. CALIBRATION: Standard solutions of analytes in ethyl acetate with internal standard. RANGE: LOD to ~1900 nmol/L. ESTIMATED LOD: 20 - 47 nmol/L depending on compound þ PRECISION ( r): ~20% varies by compound APPLICABILITY: Triazines are common agricultural herbicides. This method measures the parent compounds and two metabolites simultaneously and specifically. It is applicable to herbicide applicators, farmers, or other occupations with triazine exposure. INTERFERENCES: None identified. OTHER METHODS: This method is an adaptation of one published by Catenacci, et al. -
Concerted Nucleophilic Aromatic Substitution Reactions Simon Rohrbach+, Andrew J
Angewandte Reviews Chemie International Edition: DOI: 10.1002/anie.201902216 Nucleophilic Aromatic Substitution German Edition: DOI: 10.1002/ange.201902216 Concerted Nucleophilic Aromatic Substitution Reactions Simon Rohrbach+, Andrew J. Smith+, Jia Hao Pang+, Darren L. Poole, Tell Tuttle,* Shunsuke Chiba,* and John A. Murphy* Keywords: Dedicated to Professor Koichi concerted reactions Narasaka on the occasion of ·cSNAr mechanism · his 75th birthday Meisenheimer complex · nucleophilicaromatic substitution Angewandte Chemie &&&& 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. Int. Ed. 2019, 58,2–23 Ü Ü These are not the final page numbers! Angewandte Reviews Chemie Recent developments in experimental and computational From the Contents chemistry have identified a rapidly growing class of nucleophilic 1. Aromatic Substitution Reactions 3 aromatic substitutions that proceed by concerted (cSNAr) rather than classical, two-step, SNAr mechanisms. Whereas traditional 2. Some Contributions by SNAr reactions require substantial activation of the aromatic ring Computational Studies 6 by electron-withdrawing substituents, such activating groups are not mandatory in the concerted pathways. 3. Fluorodeoxygenation of Phenols and Derivatives 9 4. Aminodeoxygenation of Phenol 1. Aromatic Substitution Reactions Derivatives 10 Substitution reactions on aromatic rings are central to 5. Hydrides as Nucleophiles 11 organic chemistry. Besides the commonly encountered elec- trophilic aromatic substitution,[1] other mechanisms include 6. P, N, Si, C Nucleophiles 13 [2,3] SNAr nucleophilic aromatic substitutions and the distinct [4] but related SNArH and vicarious nucleophilic substitutions, 7. Organic Rearrangements via Spiro substitutions brought about through benzyne intermedi- Species: Intermediates or Transition ates,[5,6] radical mechanisms including electron transfer- States? 14 [7] based SRN1 reactions and base-promoted homolytic aro- matic substitution (BHAS) couplings,[8] sigmatropic rear- 8. -
Furan Derivatives CXCVI. Synthesis and Reactions of 3,4-Dichiorophenyl-Substituted Furocondensed Derivatives
Furan derivatives CXCVI. Synthesis and reactions of 3,4-dichIorophenyl-substituted furocondensed derivatives A. KRUTOŠÍKOVÁ, J. КО VAC, and P. BANÁK Department of Organic Chemistry, Slovak Technical University, CS-812 37 Bratislava Received 22 July 1983 The preparation of new 9-(3,4-dichlorophenyl)-furo[2',3':4,5]pyrrolo- / [l,2-i/]-l,2,4-triazolo[3' ,4"-/]-l>2>4-triazines is described. Reaction of 2- -(3,4-dichlorophenyl)-4H-furo[3,2-^]pyrrole-2-carboxhydrazide with trieth- yl orthoformate or orthoacetate afforded l,2-dihydro-7-(3,4-dichlorophenyI)- -furo[2',3' :4,5]pyrrolo[l,2-d]-l,2,4-triazine-l-one or its 4-methyl analo gue giving with phosphorus pentasulfide thiones, reacting with hydrazine to the corresponding hydrazino derivatives. The last ones with triethyl or thoformate or orthoacetate underwent cyclization reactions. Описано получение новых 9-(3,4-дихлорфенил)-фуро[2',3':4,5]пир- роло[1,2-^]-1,2,4-триазоло-[3/',4//-/]-1,2,4-триазинов. Реакция 2-(3,4-ди- хлорфенил)-4Н-фуро[3,2-Ь]пиррол-2-карбоксигидразида с триэтилор- тоформиатом или ортоацетатом вела к 1,2-дигидро-7-(3,4-дихлорфе- нил)-фуро[2/,3/:4,5]пирроло[1,2-^]-1,2,4-триазин-1-ону или его 4-ме- тильному аналогу, дающими с пентасульфидом фосфора тионы, которые взаимодействуют с гидразином с образованием соответствующих гидра зин-производных. Последние под действием триэтилортоформиата или ортоацетата подвергаются циклизации. This paper describes study on the synthesis of new 9-(3,4-dichlorophenyl)-furo- [2\3\4,5]pynxtfo[l,2-d]-l,2,4-tri^ In the last few years, considerable attention has been drawn to the synthesis of condensed heterocyclic system derived from triazine [1—5], because some of these com pounds are biologically effective [6, 7]. -
Reaction-Based Amine and Alcohol Gases Detection with Triazine Ionic
molecules Communication Communication Reaction-Based Amine and Alcohol GasesGases DetectionDetection withwith TriazineTriazine IonicIonic LiquidLiquid MaterialsMaterials Hsin-Yi LiLi andand Yen-HoYen-Ho ChuChu ** Department of Chemistry and Biochemistry, NationalNational ChungChung ChengCheng University,University, Chiayi Chiayi 62102, 62102, Taiwan; Taiwan; [email protected] ** Correspondence:Correspondence: [email protected];[email protected]; Tel.: ++86-5272-913986-5272-9139 Academic Editors: Pradip K. Bhowmik and Verónica De Zea Bermudez Academic Editors: Pradip K. Bhowmik and Verónica De Zea Bermudez Received: 31 October 2019; Accepted: 24 December 2019; Published: 26 27 December December 2019 Abstract: WeWe demonstrated in this work the use of affinity affinity ionic liquids, AIL 1 and AIL 2, for chemoselective detection detection of of amine amine and and alcohol alcohol gase gasess on a on quartz a quartz crystal crystal microbalance microbalance (QCM). (QCM). These Thesedetections detections of gaseous of gaseous amines amines and andalcohols alcohols were were achieved achieved by by nucleophilic nucleophilic aromatic aromatic substitution reactions with the electrophilic 1,3,5-triazine-based1,3,5-triazine-based AILAIL 11 thin-coatedthin-coated onon quartzquartz chips.chips. Starting with inexpensive reagents,reagents, bicyclicbicyclic imidazolium imidazolium ionic ionic liquids liquidsAIL AIL 1 1and andAIL AIL 2 were2 were readily readily synthesized synthesized in sixin six and and four four synthetic synthetic steps -
The Most Reactive Position of a 1,2,4-Triazine
1378 Vol. 35 (1987) Chem. Pharm. Bull. 35( 4 )1378-1382(1987) Studies on as-Triazine Derivatives. IX.1) Synthesis of 5-Substituted 1,2,4-Triazine Derivatives through an Addition Reaction and Subsequent Oxidation SHOETSU KONNO, SETSUYA OHBA, MATAICHI SAGI, and HIROSHI YAMANAKA* Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980, Japan (Received July 31, 1986) The addition reactions of various nucleophiles to 6-methyl-3-phenyl-1,2,4-triazine (1) were investigated and a practical preparation of 1 was developed. The reactions showed many similarities to those of quinazoline (at the 4-position) and acridine (at the 9-position). The hitherto unknown compounds 5-cyand- (3), 5-carbamoyl- (5) and 5-phenacy1-6-methyl-3-phenyl-1,2,4-triazines (11e) were synthesized. Keywords •\ 1,2,4-triazine; nucleophilic addition; aromatization; active methylene com- pound; catalytic reduction The most reactive position of a 1,2,4-triazine (as-triazine) ring is position 5, where nucleophiles can attack very easily.2) For example, 3,5,6-trichloro-as-triazine reacts with 1 mol eq of sodium methoxide to give 3,6-dichloro-5-methoxy-as-triazine exclusively.3) Further- more, the combined electron-attracting effects of three ring nitrogen atoms suggest posi- tion 5 to be highly susceptible to nucleophilic addition, when there is no leaving group at this position.4) The present paper deals with the synthesis of 5-substituted as-triazine derivatives from 6-methyl-3-phenyl-as-triazine (1). The reaction of 1 with nucleophiles came up to our expectation, as shown in Chart 1. Compound 1 reacted with sodium bisulfite in methanol to give 6-methy1-3-phenyl-2,5- dihydro-as-triazine-5-sulfonic acid (2). -
Nomenclature of Heterocyclic Compounds
Nomenclature of Heterocyclic Compounds Dr. Solomon Derese SCH 402 13 The IUPAC rules allow three nomenclatures. I. The Hantzsch-Widman Nomenclature. II. Common Names III. The Replacement Nomenclature Dr. Solomon Derese SCH 402 14 I. Hantzsch-Widman Nomenclature n = 1,2,3, …… The Hantzsch-Widman nomenclature is based on the type (Z) of the heteroatom; the ring size (n) and nature of the ring, whether it is saturated or unsaturated . This system of nomenclature applies to monocyclic three-to-ten-membered ring heterocycles. Dr. Solomon Derese SCH 402 15 I. Type of the heteroatom The type of heteroatom is indicated by a prefix as shown below for common hetreroatoms: Hetreroatom Prefix O Oxa N Aza S Thia P Phospha Dr. Solomon Derese SCH 402 16 II. Ring size (n) The ring size is indicated by a suffix according to Table I below. Some of the syllables are derived from Latin numerals, namely ir from tri, et from tetra, ep from hepta, oc from octa, on from nona, ec from deca. Table I: Stems to indicate the ring size of heterocycles Ring size Suffix Ring size Suffix 3 ir 7 ep 4 et 8 oc 5 ol 9 on Dr. Solomon Derese6 in SCH 40210 ec 17 The endings indicate the size and degree of unsaturation of the ring. Table II: Stems to indicate the ring size and degree of unsaturation of heterocycles Ring size Saturated Unsaturated Saturated (With Nitrogen) 3 -irane -irine -iridine 4 -etane -ete -etidine 5 -olane -ole -olidine 6 -inane -ine 7 -epane -epine 8 -ocane -ocine 9 -onane -onine 10 -ecane -ecine Dr.