DOCSLIB.ORG

Q3C (R8): Impurities: Guideline for Residual Solvents Step 2B

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Q3C (R8): Impurities: Guideline for Residual Solvents Step 2B 04 May 2020 EMA/CHMP/ICH/213867/2020 Committee for Medicinal Products for Human Use Q3C (R8): Impurities: guideline for residual solvents Step 2b Transmission to CHMP 30 April 2020 Adoption by CHMP 30 April 2020 Release for public consultation 4 May 2020 Deadline for comments 30 July 2020 Comments should be provided using this template. The completed comments form should be sent to [email protected] Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000An agency of the European Union © European Medicines Agency, 2020. Reproduction is authorised provided the source is acknowledged. PDE for 2-Methyltetrahydrofuran, Cyclopentyl Methyl Ether, and Tertiary-Butyl Alcohol INTERNATIONAL COUNCIL FOR HARMONISATION OF TECHNICAL REQUIREMENTS FOR PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED GUIDELINE IMPURITIES: GUIDELINE FOR RESIDUAL SOLVENTS Q3C(R8) PDE FOR 2-METHYLTETRAHYDROFURAN, CYCLOPENTYL METHYL ETHER, AND TERTIARY-BUTYL ALCOHOL Draft version Endorsed on 25 March 2020 Currently under public consultation Note : This document contains only the PDE levels for three solvents: 2- methyltetrahydrofuran, cyclopentylmethylether and tert-butanol that were agreed to be included in the ICH Q3C(R8) revision. Further to reaching Step 4, these PDEs would be integrated into a complete Q3C(R8) Guideline document. At Step 2 of the ICH Process, a consensus draft text or guideline, agreed by the appropriate ICH Expert Working Group, is transmitted by the ICH Assembly to the regulatory authorities PDE for 2-Methyltetrahydrofuran, Cyclopentyl Methyl Ether, and Tertiary-Butyl Alcohol of the ICH regions for internal and external consultation, according to national or regional procedures. PDE for 2-Methyltetrahydrofuran, Cyclopentyl Methyl Ether, and Tertiary-Butyl Alcohol IMPURITIES: GUIDELINE FOR RESIDUAL SOLVENTS PDE FOR 2-METHYLTETRAHYDROFURAN (2-MTHF), CYCLOPENTYL METHYL ETHER (CPME), AND TERTIARY BUTYL ALCOHOL (TBA) Document History Code History Date Q3C(R8) Endorsement by the Members of the ICH Assembly under 25 March Step 2 and released for public consultation (document dated 2020 14 February 2020) Legal notice: This document is protected by copyright and may, with the exception of the ICH logo, be used, reproduced, incorporated into other works, adapted, modified, translated or distributed under a public license provided that ICH's copyright in the document is acknowledged at all times. In case of any adaption, modification or translation of the document, reasonable steps must be taken to clearly label, demarcate or otherwise identify that changes were made to or based on the original document. Any impression that the adaption, modification or translation of the original document is endorsed or sponsored by the ICH must be avoided. The document is provided "as is" without warranty of any kind. In no event shall the ICH or the authors of the original document be liable for any claim, damages or other liability arising from the use of the document. The above-mentioned permissions do not apply to content supplied by third parties. Therefore, for documents where the copyright vests in a third party, permission for reproduction must be obtained from this copyright holder. PDE for 2-Methyltetrahydrofuran, Cyclopentyl Methyl Ether, and Tertiary-Butyl Alcohol 1 PART VI: 2 IMPURITIES: RESIDUAL SOLVENTS (MAINTENANCE) 3 PDE FOR 2-METHYLTETRAHYDROFURAN, CYCLOPENTYL METHYL ETHER, 4 AND TERTIARY-BUTYL ALCOHOL 5 2-METHYLTETRAHYDROFURAN 6 Introduction 7 2-Methyltetrahydrofuran (2-MTHF, synonyms: 2-Methyloxolane, Tetrahydrosylvan; Tetrahydro- 8 2-methylfuran; CAS Number 96-47-9) is a colourless, volatile liquid with ether-like odour. 2- 9 MTHF is an organic solvent usually synthesized as a racemic mixture consisting of two 10 enantiomeric forms ((S)+ and (R)-). Solubility in water is limited and decreases with increasing 11 temperature. It has a vapour pressure of 136 mbar (20°C) (1). 12 2-MTHF is increasingly used as a catalytic solvent in exchange of Tetrahydrofuran (THF) and is 13 much less miscible with water compared to THF. 14 Genotoxicity 15 2-MTHF was not mutagenic in the AMES bacterial reverse mutation assay with Salmonella 16 typhimurium (3) and Escherichia coli WP2 uvrA (2). 2-MTHF was also tested in vitro in a L5178Y 17 mouse lymphoma cell TK+/- assay (MLA) (3), and a chromosome aberration assay in human 18 peripheral blood lymphocytes (2), and in vivo in a bone marrow micronucleus test integrated into 19 a 3-month oral repeated-dose toxicity study in rats (2). All test results were negative except for the 20 MLA in the presence of S9, which was considered inconclusive without further explanation (3). In 21 conclusion, there is no evidence that 2-MTHF is genotoxic. 22 Carcinogenicity 23 No data for 2-MTHF are available. 24 Reproductive toxicity 25 No reliable information about reproductive toxicity is available. In an acute embryo toxicity and 26 teratogenicity test in zebrafish, 2-MTHF was tested at concentrations ranging from 860 – 8600 27 mg/L (4). Acute embryo toxicity was observed for 2-MTHF at a nominal LC50 value of 2980 mg/L. 28 Sublethal effects were also observed, such as an increase in oedema at nominal concentrations ≥ 29 1720 mg/L, as well as an increased number of embryos without detectable blood circulation and 1 PDE for 2-Methyltetrahydrofuran, Cyclopentyl Methyl Ether, and Tertiary-Butyl Alcohol 30 insufficient pigmentation at a nominal concentration of 2580 mg/L. Teratogenic effects were not 31 observed with 2-MTHF in this assay. 32 Repeated-dose toxicity 33 Two 3-month oral repeated-dose toxicity studies in Crl:CD (SD) rats have been described with 2- 34 MTHF; one without an additional recovery period (2) and one with an additional 1-month recovery 35 period (5). The top dose in the first study was 26 mg/kg/day (2) and in the second study 1000 36 mg/kg/day (5). 2-MTHF treatment-related observations were not seen in the first study (2). In the 37 second study, groups of 10 male and 10 female rats per dose group were treated with doses of 80, 38 250, 500 and 1000 mg/kg/day (5). An additional 1-month treatment-free recovery period was added 39 for 5 animals/sex of the control and the high dose groups. Treatment-related observations were 40 generally seen only at doses ≥ 500 mg/kg/day. Besides slight effects on kidney weights (increased 41 at ≥ 500 mg/kg/day), blood cholesterol (increase at 1000 mg/kg/day) and prothrombin time 42 (decreased at ≥ 500 mg/kg/day), the only test article-related microscopic observation was 43 hepatocellular centrilobular hypertrophy at 1000 mg/kg/day. However, no effects were observed in 44 the recovery group and the observed effects can therefore be regarded as completely reversible (5). 45 The NOEL in the second study was considered to be 250 mg/kg/day. 46 The NOEL of 250 mg/kg/day was used in the PDE calculation: 250 x 50 47 PDE = = 50 mg/day 5 x 10 x 5 x 1 x 1 48 F1 = 5 to account for extrapolation from rats to humans 49 F2 = 10 to account for differences between individual humans 50 F3 = 5 for a 3-month study in rodents 51 F4 = 1 because no severe effects were observed 52 F5 = 1 because a NOEL was established 53 Conclusion 54 The calculated PDE for 2-MTHF is 50 mg/day based upon the NOEL of the rat sub-chronic oral 55 study. Since the proposed PDE is greater than or equal to 50 mg/day, it is recommended that 2- 56 MTHF be placed into Class 3 “Solvents with low toxic potential” in Table 3 in the ICH Impurities: 57 Residual Solvents Guideline. 58 2 PDE for 2-Methyltetrahydrofuran, Cyclopentyl Methyl Ether, and Tertiary-Butyl Alcohol 59 References 60 1. Aycock DF. Solvent applications of 2-methyltetrahydrofuran in organometallic and 61 biphasic reactions. Org. Process Res. Dev. 2007;11:156-159. 62 2. Antonucci V, Coleman J, Ferry JB, Johnson N, Mathe M, Scott JP, et al. Toxicological 63 assessment of 2-methyltetrahydrofuran and cyclopentyl methyl ether in support of their use 64 in pharmaceutical chemical process development. Org. Process Res. Dev. 2011;15:939-41. 65 3. Seifried HE, Seifried RM, Clarke JJ, Junghans TB, Sanet RH. A compilation of two decades 66 of mutagenicity test results with the Ames Salmonella typhimurium and L5178Y mouse 67 lymphoma cell mutation assays. Chem Res Toxicol 2006;19(5):627-44. 68 4. Bluhm K, Seiler TB, Anders N, Klankermayer J, Schaeffer A, Hollert H. Acute embryo 69 toxicity and teratogenicity of three potential biofuels also used as flavor or solvent. Sci 70 Total Environ. 2016;566-7:786-95. 71 5. Parris P, Duncan JN, Fleetwood A, Beierschmitt WP. Calculation of a permitted daily 72 exposure value for the solvent 2-methyltetrahydrofuran. Regul Toxicol Pharmacol 73 2017;87:54-63. 74 75 3 PDE for 2-Methyltetrahydrofuran, Cyclopentyl Methyl Ether, and Tertiary-Butyl Alcohol 76 CYCLOPENTYL METHYL ETHER 77 Introduction 78 Cyclopentyl methyl ether (CPME: CAS Number 5614-37-9) is used in pharmaceutical chemical 79 development as an alternative to its more common analogues such as tetrahydrofuran and tert-butyl 80 methyl ether (1,2). 81 The vapour pressure of CPME is 44.9 mmHg at 25°C, the Log Pow is 1.59 and the water solubility 82 is 1.1 g/100 g (23 °C) (3,4). 83 CPME is classified as an irritant to skin (H315) and eye (H319) in accordance with EC No 84 1272/2008, in the Globally Harmonized System of Classification and Labelling of Chemicals 85 (GHS).
Load more

Recommended publications
  • Energy-Saving Reduced-Pressure Extractive Distillation with Heat
    Energy-Saving Reduced-Pressure Extractive Distillation with Heat Integration for Separating the Biazeotropic Ternary Mixture Tetrahydrofuran–Methanol–Water Jinglian Gu, Xinqiang You, Changyuan Tao, Jun Li, Vincent Gerbaud To cite this version: Jinglian Gu, Xinqiang You, Changyuan Tao, Jun Li, Vincent Gerbaud. Energy-Saving Reduced- Pressure Extractive Distillation with Heat Integration for Separating the Biazeotropic Ternary Mixture Tetrahydrofuran–Methanol–Water. Industrial and engineering chemistry research, American Chemical Society, 2018, 57 (40), pp.13498-13510. 10.1021/acs.iecr.8b03123. hal-01957130 HAL Id: hal-01957130 https://hal.archives-ouvertes.fr/hal-01957130 Submitted on 17 Dec 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. OATAO is an open access repository that collects the work of Toulouse researchers and makes it freely available over the web where possible This is an author’s version published in: http://oatao.univ-toulouse.fr/21066 Official URL: https://doi.org/10.1021/acs.iecr.8b03123 To cite this version: Gu, Jinglian and You, Xinqiang and Tao, Changyuan and Li, Jun and Gerbaud, Vincent Energy-Saving Reduced-Pressure Extractive Distillation with Heat Integration for Separating the Biazeotropic Ternary Mixture Tetrahydrofuran–Methanol–Water.
    [Show full text]
  • Cyclopentyl Methyl Ether (CPME)
    Korean J. Chem. Eng., 34(2), 463-469 (2017) pISSN: 0256-1115 DOI: 10.1007/s11814-016-0265-5 eISSN: 1975-7220 INVITED REVIEW PAPER Measurement and correlation of the isothermal VLE data for the binary mixtures of cyclopentene (CPEN)+cyclopentyl methyl ether (CPME) Wan Ju Jeong and Jong Sung Lim† Department of Chemical and Biomolecular Engineering, Sogang University, C.P.O. Box 1142, Seoul 04107, Korea (Received 2 August 2016 • accepted 20 September 2016) Abstract−The isothermal vapor-liquid equilibrium data for the binary systems of cyclopentene (1)+cyclopentyl methyl ether (2) were measured at 313.15, 323.15, 333.15, 343.15 and 353.15 K using a dynamic-type equilibrium apparatus and online gas chromatography analysis. For all the measured VLE data consistency tests were performed for the verifi- cation of data using Barker’s method and the ASPEN PLUS Area Test method. All the resulting average absolute val- δ γ γ ues of residuals [ ln ( 1/ 2)] for Barker’s method and D values for the ASPEN PLUS area test method were com- paratively small. So, the VLE data reported in this study are considered to be acceptable. This binary system shows neg- ative deviation from Raoult’s law and does not exhibit azeotropic behavior at whole temperature ranges studied here. The measured data were correlated with the P-R EoS using the Wong-Sandler mixing rule. The overall average relative deviation of pressure (ARD-P (%)) between experimental and calculated values was 0.078% and that of vapor phase compositions (ARD-y (%)) was 0.452%. Keywords: Vapor Liquid Equilibria (VLE), Cyclopentyl Methyl Ether (CPME), Cyclopentene (CPEN), Peng-Robinson Equation of State (PR-EoS), Wong-Sandler Mixing Rule (WS-MR) INTRODUCTION however, have some disadvantages because they use dimethyl sul- fate and methyl iodide as a reactant, respectively, which are muta- Ethers are widely used in organic chemistry and biochemistry.
    [Show full text]
  • Poly(Ethylene Oxide-Co-Tetrahydrofuran) and Poly(Propylene Oxide-Co-Tetrahydrofuran): Synthesis and Thermal Degradation
    Revue Roumaine de Chimie, 2006, 51(7-8), 781–793 Dedicated to the memory of Professor Mircea D. Banciu (1941–2005) POLY(ETHYLENE OXIDE-CO-TETRAHYDROFURAN) AND POLY(PROPYLENE OXIDE-CO-TETRAHYDROFURAN): SYNTHESIS AND THERMAL DEGRADATION Thomas HÖVETBORN, Markus HÖLSCHER, Helmut KEUL∗ and Hartwig HÖCKER Lehrstuhl für Textilchemie und Makromolekulare Chemie der Rheinisch-Westfälischen Technischen Hochschule Aachen, Pauwelsstr. 8, 52056 Aachen, Germany Received January 12, 2006 Copolymers of tetrahydrofuran (THF) and ethylene oxide (EO) (poly(THF-co-EO) and THF and propylene oxide (PO) (poly(THF-co-PO) were obtained by cationic ring opening polymerization of the monomer mixture at 0°C using boron trifluoride etherate (BF3.OEt2) as the initiator. From time conversion plots it was concluded that both monomers are consumed from the very beginning of the reaction and random copolymers are obtained. For poly(THF-co-PO) the molar ratio of repeating units was varied from [THF]/[PO] = 1 to 10; the molar ratio of monomers in the feed corresponds to the molar ratio of repeating units in the copolymer. Thermogravimetric analysis of the copolymers revealed that both poly(THF-co-EO) and poly(THF-co-PO) decompose by ca. 50°C lower than poly(THF) and by ca. 100°C lower than poly(EO); 50% mass loss is obtained at T50 = 375°C for poly(EO), T50 = 330°C for poly(THF) and at T50 = 280°C for both copolymers. The [THF]/[PO] ratio does not influence the decomposition temperature significantly as well. For the copolymers the activation energies of the thermal decomposition (Ea) were determined experimentally from TGA measurements and by density functional calculations on model compounds on the B3LYP/6-31+G* level of theory.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7.494,962 B2 Kinet Al
    USOO74949.62B2 (12) United States Patent (10) Patent No.: US 7.494,962 B2 Kinet al. (45) Date of Patent: Feb. 24, 2009 (54) SOLVENTS CONTAINING CYCLOAKYL (56) References Cited ALKYLETHERS AND PROCESS FOR PRODUCTION OF THE ETHERS U.S. PATENT DOCUMENTS 3496,223 A * 2/1970 Mitchell et al. ............... 562/22 (75) Inventors: Idan Kin, Ottawa (CA); Genichi Ohta, Tokyo (JP); Kazuo Teraishi, Tokyo (JP); Kiyoshi Watanabe, Tokyo (JP) (Continued) (73) Assignee: Zeon Corporation, Tokyo (JP) FOREIGN PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this EP 587434 A1 3, 1994 patent is extended or adjusted under 35 U.S.C. 154(b) by 349 days. (Continued) (21) Appl. No.: 10/481,340 OTHER PUBLICATIONS (22) PCT Filed: Jun. 27, 2002 Edited by Kagaku Daijiten Henshu Iinkai, “Kagaku Daijiten 9”. (86). PCT No.: PCT/UP02/06501 Kyoritsu Shuppan Co., Ltd., Aug. 25, 1962, p. 437, "Yozai'. (Continued) S371 (c)(1), (2), (4) Date: Sep. 24, 2004 Primary Examiner Gregory E Webb (74) Attorney, Agent, or Firm—Birch, Stewart, Kolasch & (87) PCT Pub. No.: WO03/002500 Birch, LLP PCT Pub. Date: Jan. 9, 2003 (57) ABSTRACT (65) Prior Publication Data The present inventions are (A) a solvent comprising at least US 2005/OO65060A1 Mar. 24, 2005 one cycloalkyl alkyl ether (1) represented by the general O O formula: R1-O R2 (wherein R1 is cyclopentyl or the like: (30) Foreign Application Priority Data and R2 is C1-10 alkyl or the like); (B) a method of prepara Jun. 28, 2001 (JP) ............................. 2001-196766 tions the ethers (1) characterized by reacting an alicyclic Oct.
    [Show full text]
  • Tetrahydrofuran
    SOME CHEMICALS THAT CAUSE TUMOURS OF THE URINARY TRACT IN RODENTS VOLUME 119 This publication represents the views and expert opinions of an IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, which met in Lyon, 6–13 June 2017 LYON, FRANCE - 2019 IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS TETRAHYDROFURAN 1. Exposure Data Boiling point: 65–66 °C (EPA, 2012) Melting point: −108.44 °C (ECHA, 2018) 1.1 Identification of the agent Relative density: 0.883 at 25 °C (water, 1) (ECHA, 2018) 1.1.1 Nomenclature Solubility: Miscible in water (ECHA, 2018) Chem. Abstr. Serv. Reg. No.: 109-99-9 Volatility: Vapour pressure, 19.3 kPa at 20 °C (IPCS, 1997) EC/List No.: 203-726-8 Relative vapour density: 2.5 (air = 1); relative Chem. Abstr. Serv. name: Tetrahydrofuran density of the vapour/air mixture at 20 °C IUPAC systematic name: Oxolane (air = 1): 1.28 (IPCS, 1997) Synonyms: Butane alpha,delta-oxide; butane, Stability: Tetrahydrofuran is prone to oxida- 1,4-epoxy-; cyclotetramethylene oxide; dieth- tion to peroxides, butyric acid, butyralde- ylene oxide; 1,4-epoxybutane; furan, tetra- hyde, and related compounds, mainly on hydro-; furanidine; hydrofuran; oxacyclo- ageing and in the presence of light, heat, pentane; tetramethylene oxide; THF and moisture. The formation of peroxides can be retarded by adding stabilizers such as 1.1.2 Structural and molecular formulae, and hydroquinone or 2,6-di-tert-butyl-p-cresol at relative molecular mass 250 mg/kg (Coetzee & Chang, 1985; Müller, 2012). O Flash point: −14.5 °C
    [Show full text]
  • United States Patent 0 Ice Patented Jan
    3,489,528 United States Patent 0 ice Patented Jan. 13, 1970 1 2 number of (BHZNHZ) groups, but the product is con 3,489,528 PREPARATION OF POLYAMINOBORANES sistent in composition, as shown by infra-red and ele William E. Zanieski, Pittsburgh, Pa., assignor to Mine mental analyses, and the average value of n is about 4. Safety Appliances Company, a corporation of In another example a solution of THF-EH3 contain— Pennsylvania ing 2.99 g. of B2H6 in 150 ml. of THF was prepared N0 Drawing. Filed Apr. 5, 1965, Ser. No. 445,707 in the same manner as the previous example and the Int. Cl. C01b 21/00 solution was warmed to -30° C. 3.12 g. of gaseous US. Cl. 23—358 6 Claims ammonia was bubbled into and dissolved in the solution at —30° C. and the resultant clear solution was warmed to 0° C, at which temperature hydrogen was evolved and polyaminoborane, identical to that obtained in the ABSTRACT OF THE DISCLOSURE previous example, precipitated from the reaction mix Ammonia and diborane are reacted in tetrahydrofuran ture. at a temperature below about —30° C.; polyaminoboranes ‘Although the invention is not limited to any particular are precipitated when the reaction mixture is warmed. 15 reaction mechanism, it appears that the reaction of NH3 Aging of an ammonia solution of the polyaminoboranes and BZHS in THF forms an intermediate that is formed so produced yields an ammonia insoluble, more highly and is stable only at temperatures below about —30° C. polymerized polyaminoborane. and that this intermediate decomposes at temperatures above about —30° C.
    [Show full text]
  • Tetrahydrofuran (THF)
    Tetrahydrofuran (THF) Typical Physical Properties of THF Molecular Weight 72.11 g/mol Empirical Formula C4H8O Appearance Colorless Freezing Point ‐108°C (‐ 164.4°F) Flash Point – Closed Cup ‐20°C (‐4°F) Boiling Point @ 760mmHg 66°C (150.8°F) Autoignition Temperature 230°C (446°F) Density @ 20°C 0.89 kg/l Tetrahydrofuran (THF) is a clear, colorless liquid with 7.43 lb/gal an ether‐like odor. The principal end uses of THF Vapor Pressure @ 20°C 193 hPa include PTMEG, pharmaceutical solvent, adhesives, PVC cement and magnetic tape. Due to its' tendency Evaporation Rate (nBuAc = 1) 8 to form peroxides during storage, THF is inhibited with Solubility @ 20°C (in Water) Complete BHT. Refractive Index @ 20°C 1.407 CAS number Viscosity @ 20°C 0.516 cP Lower Flammability in Air 1.5% v/v 109‐99‐9 Upper Flammability in Air 12.4% v/v Synonyms Note: The properties reported above are typical physical properties. Monument Chemical in no way guarantees that the 1,4‐epoxybutane; Cyclotetramethylene oxide; Butane product from any particular lot will conform exactly to the given .alpha.,.delta.‐oxide values. Health and safety information Under current U.S. OSHA's Hazardous Communication program THF is classified as a flammable liquid, can cause eye and respiratory irritation. Keep the material away from heat sources, hot surfaces, open flames, and sparks. Use only in a well‐ventilated area. Observe good industrial hygiene practices and use appropriate Personal Protective Equipment. For full safety information please refer to the Safety Data Sheet. Storage and Handling specific product Technical Data Sheet (TDS) is accurate, but makes no representations as to the sufficiency or THF should be stored only in tightly closed, properly completeness of the product or information in this TDS vented containers away from heat, sparks, open flame and makes no commitment to correct or bring up‐to‐date or strong oxidizing agents.
    [Show full text]
  • Contribution of Cyclopentyl Methyl Ether (CPME) to Green Chemistry
    sustainability / green chemistry Industry perspective Shunji Sakamoto Contribution of Cyclopentyl Methyl Ether (CPME) to Green Chemistry Shunji sakamoto Specialty Chemicals Division, ZEON CORPORATION, 1-6-2 Marunouchi, Chiyoda-ku, Tokyo, 1008246, Japan easy peroxide formation and water miscibility, the demand KEyWORDS for CPME has steadily been growing in the pharmaceutical Cyclopentyl methyl ether, CPME, Green Chemistry, industry as well as in the electronic and fragrance solvent, process, ICH. industries. Also, CPME has been registered or listed in the corresponding legislations for new chemical substances of United States of America, Canada, European Union, ABSTRACT Japan, South Korea, China and Chinese Taipei, and is commercially available in these countries and regions as Cyclopentyl methyl ether (CPME) is an alternative well as others including India. solvent and has preferable properties including higher In this article, I answer the question why CPME is “Green” hydrophobicity, lower formation of peroxides and better even though it is derived from petroleum. stability under acidic and basic conditions compared to other traditional ether solvents such as tetrahydrofuran. Due to the above unique properties, CPME has particular UNIQUE FEATURES OF CPME 24 advantages and renders some conventional reaction sequences in one pot or easier process as a result of CPME is an asymmetric aliphatic ether having a cyclopentyl solvent unification and facile isolation of the products, group. It has seven unique features attributed to its structure which contribute to Green Chemistry as well as to (Table 1). process innovation. CPME meets eight definitions out of the 12 Principles of Green Chemistry (1) because of Extremely lower miscibility with water the above characteristics as well as its manufacturing The solubility of CPME in water is only 1.1% and that of water process and its applications.
    [Show full text]
  • 1- MANUFACTURING of MATERIAL BASED HYDROGEN FUEL for LIGHTWEIGHT VEHICLES by ALI KHAGHANI a Thesis
    MANUFACTURING OF MATERIAL BASED HYDROGEN FUEL FOR LIGHTWEIGHT VEHICLES Item Type text; Electronic Thesis Authors KHAGHANI, ALI Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 23/09/2021 12:36:34 Link to Item http://hdl.handle.net/10150/613155 MANUFACTURING OF MATERIAL BASED HYDROGEN FUEL FOR LIGHTWEIGHT VEHICLES By ALI KHAGHANI ____________________ A Thesis Submitted to The Honors College In Partial Fulfillment of the Bachelors degree With Honors in Chemical Engineering THE UNIVERSITY OF ARIZONA M A Y 2016 Approved by: ____________________________ Dr. Kimberly Ogden Chemical and Environmental Engineering -1- Abstract Vehicles powered by hydrogen fuel cells store hydrogen as a cooled liquid at 20 degrees kelvin or a compressed gas at 10,000 pounds per square inch. An alternative that eliminates the need for these extremes of temperature and pressure is to heat a compound containing covalently bonded hydrogen, causing it to release the hydrogen to the fuel cell. Ammonia borane, which is stable at ambient conditions, requires minimal energy for dehydrogenation, and is rich in hydrogen, is a possible storage medium for hydrogen. If a viable storage system could be engineered, demand for ammonia borane as a source of hydrogen would increase. The goal of this project is to develop a processing plant and to optimize design specifications for scaling up processing of ammonia borane through the metathesis reaction pathway.
    [Show full text]
  • Pressure-Swing-Distillation Process for Separation of Tetrahydrofuran/Methanol
    Pressure-Swing-Distillation Process for Separation of Tetrahydrofuran/Methanol Maradiya jay, Mehulkumar sutariya Sardar Vallabhbhai National Institute Of Technology, Surat Email: [email protected] Background Tetrahydrofuran (THF) is one of the most commonly used solvents in the chemical and the pharmaceutical industries due to its excellent dissolution ability. The production of steroid drugs faces the problem of separating solvent which contains THF and methanol. The separation and recycle of THF and methanol are of high economic significance and environmental importance. However, difficulty occur in the separation process because a minimum-boiling azeotrope is formed in the binary system. The pressure-swing-distillation (PSD) process, commonly used to separate azeotropic mixtures based on the shift of the relative volatilities and azeotropic compositions by changing the system’s pressure, is another suitable separation method for the separation of azeotropes. Efficient separation is achieved by two columns operating at two different pressure. Azeotropic data of Tetrahydrofuran/Methanol Figures: Effect of pressure on azeotropic composition and temperature. As shown in the figure, at atmospheric pressure (1 atm) azeotropic composition is near 45 mol% of Tetrahydrofuran and and 55 mol% Methanol. At 10 atm the azeotropic composition is changed to near 21 mol% of Tetrahydrofuran and 79 mol% of Methanol. Description of Flow-Sheet In this flow-sheet We use two distillation column with different pressure (1 atm and 10 atm). In low pressure column we enter a feed; This feed are concentrated near the azeotropic composition at 1 atm,and the 99.9 mol% Methanol are collected from the bottom. The top stream of low pressure column are now enter to the high pressure column where it’s composition are changed with the azeotropic composition at 10 atm, and the pure Tetrahydrofuran are collected from the bottom of that column and the top stream of high pressure column are recycled to the low pressure column.
    [Show full text]
  • Material Safety Data Sheet
    MATERIAL SAFETY DATA SHEET MSDS Number: 1201E Section 1 PRODUCT AND COMPANY IDENTIFICATION Trade Name: OATEY CPVC MEDIUM ORANGE CEMENT Product Nos.: 31127, 31128(TV), 31129(TV), 31130, 31131, 32212, 32213, 32214, 32215, 31151, 30234 Product Use: Cement for CPVC Plastic Pipe Formula: CPVC Resin in Solvent Solution Synonyms: CPVC Plastic Pipe Cement Firm Name & Oatey Company 4700 West 160th Street, Cleveland, Ohio 44135 Address: www.oatey.com Firm Phone No: (216) 267-7100 Emergency Phone For Emergency First Aid call 1-877-740-5015. For chemical transportation Nos.: emergencies ONLY, call Chemtrec at 1-800-424-9300. Outside the U.S. 1- 703-527-3887. Prepared by: Technical Department Preparation Date: 07/30/2012 Section 2 HAZARDS IDENTIFICATION Emergency Overview: Orange liquid with an ether-like odor. Extremely flammable liquid and vapor. Vapors may cause flash fire. May cause eye and skin irritation. Inhalation of vapors or mist may cause respiratory irritation and central nervous system effects. Swallowing may cause irritation, nausea, vomiting, diarrhea and kidney or liver disorders. Aspiration hazard. May be fatal if swallowed. Symptoms may be delayed. Section 3 COMPOSITION/INFORMATION ON INGREDIENTS INGREDIENTS: %wt/wt : CAS NUMBER: ACGIH TLV TWA: OSHA PEL TWA OTHER: Tetrahydrofuran 25 – 45% 109-99-9 50 ppm(skin) 200 ppm 25 ppm (Mfg) 100 ppm STEL Methyl Ethyl Ketone 10 – 30% 78-93-3 200 ppm 200 ppm None 300 ppm Acetone 5 - 20% 67-64-1 500 ppm 1000 ppm None 750 ppm STEL CPVC Resin 12 – 20% 68648-82-8 10 mg/m3 None None (Non-hazardous) Established Cyclohexanone 5 – 15% 108-94-1 20 ppm(skin) 50 ppm None 50 ppm STEL Amorphous Fumed Silica 1 - 5% 112945-52-5 10 mg/m3 None None (Non-hazardous) Established a OSHA Hazard Classification: Flammable, irritant, organ effects Section 4 FIRST AID MEASURES Skin: Remove contaminated clothing immediately.
    [Show full text]
  • Supporting Information Structurally
    Electronic Supplementary Material (ESI) for Chemical Science. This journal is © The Royal Society of Chemistry 2018 Supporting Information Structurally Characterized Terminal Manganese(IV)-Oxo Tris(alkoxide) Complex Robert L. Halbach, David Gygi, Eric D. Bloch, Bryce L. Anderson and Daniel G. Nocera* Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138–2902 Email: [email protected] Index Page General methods S2–S3 X-ray crystallographic details S4 SQUID magnetometry details S4 Syntheses and characterization of compounds S5–S6 ESI-MS spectrum of compounds 3 and 18Ooxo-enriched 3 S7 X-ray crystallographic table S8 X-ray structures of compounds 1, 2, and 3 S9–S11 Infrared spectra of compounds 1, 2, and 3 S12–S13 SQUID magnetization data for 3 S14–S15 UV-vis absorption spectra of compound 3 S16 NMR spectrum of reaction of 3 with cyclohexadiene S17 S1 General methods Reactions involving air-sensitive materials were performed in a nitrogen-filled glovebox. Glassware and magnetic teflon stirbars were dried at 150 °C for at least 12 h prior to use. Pentane was dried and distilled over sodium and stored over 4-A molecular sieves. Diethylether (Et2O), tetrahydrofuran (THF) and tetrahydrofuran-d8 (THF-d8) were dried and distilled over sodium and benzophenone and stored over 4-A molecular sieves for at least 12 h. Butyronitrile was distilled from P2O5 and stored over 4-A molecular sieves for several days prior to use. The reagents 15-crown-5-ether (15-C-5) and 1,4-cyclohexadiene (CHD) were rigorously freeze-pump-thawed under high-vacuum (10–7 mTorr) several times and stored over activated 4-A molecular sieves for several days prior to use.
    [Show full text]