Highly Functionalized Piperidine Generation Via Pyridine Repolarization and Hyper-Distorted Allyl Complexes of {Tpw(NO){Pme3)}
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Chapter 13 Reactions of Arenes Electrophilic Aromatic Substitution
CH. 13 Chapter 13 Reactions of Arenes Electrophilic Aromatic Substitution Electrophiles add to aromatic rings in a fashion somewhat similar to the addition of electrophiles to alkenes. Recall: R3 R4 E Y E Y C C + E Y R1 C C R4 R1 C C R4 − R2 R1 δ+ δ R2 R3 R2 R3 In aromatic rings, however, we see substitution of one of the benzene ring hydrogens for an electrophile. H E + E Y + Y H δ+ δ− The mechanism is the same regardless of the electrophile. It involves two steps: (1) Addition of the electrophile to form a high-energy carbocation. (2) Elimination of the proton to restore the aromatic ring system. H H H H slow E Y + Y step 1 + E δ+ δ− high energy arenium ion H H step 2 fast E E + Y + Y H The first step is the slow step since the aromaticity of the benzene ring system is destroyed on formation of the arenium ion intermediate. This is a high energy species but it is stabilized by resonance with the remaining two double bonds. The second step is very fast since it restores the aromatic stabilization. 1 CH. 13 H H H H H H E E E There are five electrophilic aromatic substitution reactions that we will study. (1) Nitration H NO2 H2SO4 + HNO3 (2) Sulfonation H SO3H + H2SO4 (3) Halogenation with bromine or chlorine H X FeX3 X = Br, Cl + X2 (4) Friedel-Crafts Alkylation H R AlX + RX 3 (5) Friedel-Crafts Acylation O H O C AlX3 R + Cl C R 2 CH. -
Phencyclidine (PCP) Abuse: an Appraisal
PHENCYCLIDINE Latest Revision: May 16, 2005 1. SYNONYMS CFR: Phencyclidine CAS #: Base: 77-10-1 Hydrochloride: 956-90-1 Other Names: 1-(1-Phenylcyclohexyl) piperidine PCP Angel dust CI-395 Sernylan Sernyl 2. CHEMICAL AND PHYSICAL DATA 2.1. CHEMICAL DATA Form Chemical Formula Molecular Weight Melting Point (°C) Base C17H25N 243.4 46-46.5 Hydrochloride C17H26NCl 279.9 233-235 2.2. SOLUBILITY Form A C E H M W Base FS FS FS FS S VSS Hydrochloride SS FS I I FS FS A = acetone, C = chloroform, E = ether, H = hexane, M = methanol and W = water, VS = very soluble, FS = freely soluble, S = soluble, PS = sparingly soluble, SS = slightly soluble, VSS = very slightly soluble and I = insoluble 3. SCREENING TECHNIQUES 3.1. COLOR TESTS REAGENT COLOR PRODUCED p-Dimethylaminobenzaldehyde Red 3.2. CRYSTAL TESTS REAGENT CRYSTALS FORMED Potassium permanganate Bow-tie shaped 3.3. THIN-LAYER CHROMATOGRAPHY Visualization Acidified iodoplatinate spray Dragendorff spray COMPOUND RELATIVE R1 System System System TLC17 TLC11 TLC16 piperidine 0.4 0.2 0.1 PCP 1.0 1.0 1.0 piperidinocyclohexylcarbonitrile (PCC) 4.5 1.7 1.7 Both iodoplatinate and Dragendorff sprays will detect the three components. Iodine vapor produces a white spot outlined in brown for PCC, where as PCP and piperidine both give brown spots. 3.4. GAS CHROMATOGRAPHY Method PCP-GCS1 Instrument: Gas chromatograph operated in split mode with FID Column: 5% phenyl/95% methyl silicone 12 m x 0.2 mm x 0.33 µm film thickness Carrier gas: Helium at 1.0 mL/min Temperatures: Injector: 270°C Detector: 280°C Oven program: 1) 175°C initial temperature for 1.0 min 2) Ramp to 275°C at 15°C/min 3) Hold final temperature for 3.0 min Injection Parameters: Split Ratio = 60:1, 1 µL injected Samples are to be dissolved or diluted in chloroform and filtered. -
Fatty Acid Biosynthesis
BI/CH 422/622 ANABOLISM OUTLINE: Photosynthesis Carbon Assimilation – Calvin Cycle Carbohydrate Biosynthesis in Animals Gluconeogenesis Glycogen Synthesis Pentose-Phosphate Pathway Regulation of Carbohydrate Metabolism Anaplerotic reactions Biosynthesis of Fatty Acids and Lipids Fatty Acids contrasts Diversification of fatty acids location & transport Eicosanoids Synthesis Prostaglandins and Thromboxane acetyl-CoA carboxylase Triacylglycerides fatty acid synthase ACP priming Membrane lipids 4 steps Glycerophospholipids Control of fatty acid metabolism Sphingolipids Isoprene lipids: Cholesterol ANABOLISM II: Biosynthesis of Fatty Acids & Lipids 1 ANABOLISM II: Biosynthesis of Fatty Acids & Lipids 1. Biosynthesis of fatty acids 2. Regulation of fatty acid degradation and synthesis 3. Assembly of fatty acids into triacylglycerol and phospholipids 4. Metabolism of isoprenes a. Ketone bodies and Isoprene biosynthesis b. Isoprene polymerization i. Cholesterol ii. Steroids & other molecules iii. Regulation iv. Role of cholesterol in human disease ANABOLISM II: Biosynthesis of Fatty Acids & Lipids Lipid Fat Biosynthesis Catabolism Fatty Acid Fatty Acid Degradation Synthesis Ketone body Isoprene Utilization Biosynthesis 2 Catabolism Fatty Acid Biosynthesis Anabolism • Contrast with Sugars – Lipids have have hydro-carbons not carbo-hydrates – more reduced=more energy – Long-term storage vs short-term storage – Lipids are essential for structure in ALL organisms: membrane phospholipids • Catabolism of fatty acids –produces acetyl-CoA –produces reducing -
APPENDIX G Acid Dissociation Constants
harxxxxx_App-G.qxd 3/8/10 1:34 PM Page AP11 APPENDIX G Acid Dissociation Constants § ϭ 0.1 M 0 ؍ (Ionic strength ( † ‡ † Name Structure* pKa Ka pKa ϫ Ϫ5 Acetic acid CH3CO2H 4.756 1.75 10 4.56 (ethanoic acid) N ϩ H3 ϫ Ϫ3 Alanine CHCH3 2.344 (CO2H) 4.53 10 2.33 ϫ Ϫ10 9.868 (NH3) 1.36 10 9.71 CO2H ϩ Ϫ5 Aminobenzene NH3 4.601 2.51 ϫ 10 4.64 (aniline) ϪO SNϩ Ϫ4 4-Aminobenzenesulfonic acid 3 H3 3.232 5.86 ϫ 10 3.01 (sulfanilic acid) ϩ NH3 ϫ Ϫ3 2-Aminobenzoic acid 2.08 (CO2H) 8.3 10 2.01 ϫ Ϫ5 (anthranilic acid) 4.96 (NH3) 1.10 10 4.78 CO2H ϩ 2-Aminoethanethiol HSCH2CH2NH3 —— 8.21 (SH) (2-mercaptoethylamine) —— 10.73 (NH3) ϩ ϫ Ϫ10 2-Aminoethanol HOCH2CH2NH3 9.498 3.18 10 9.52 (ethanolamine) O H ϫ Ϫ5 4.70 (NH3) (20°) 2.0 10 4.74 2-Aminophenol Ϫ 9.97 (OH) (20°) 1.05 ϫ 10 10 9.87 ϩ NH3 ϩ ϫ Ϫ10 Ammonia NH4 9.245 5.69 10 9.26 N ϩ H3 N ϩ H2 ϫ Ϫ2 1.823 (CO2H) 1.50 10 2.03 CHCH CH CH NHC ϫ Ϫ9 Arginine 2 2 2 8.991 (NH3) 1.02 10 9.00 NH —— (NH2) —— (12.1) CO2H 2 O Ϫ 2.24 5.8 ϫ 10 3 2.15 Ϫ Arsenic acid HO As OH 6.96 1.10 ϫ 10 7 6.65 Ϫ (hydrogen arsenate) (11.50) 3.2 ϫ 10 12 (11.18) OH ϫ Ϫ10 Arsenious acid As(OH)3 9.29 5.1 10 9.14 (hydrogen arsenite) N ϩ O H3 Asparagine CHCH2CNH2 —— —— 2.16 (CO2H) —— —— 8.73 (NH3) CO2H *Each acid is written in its protonated form. -
Ganic Compounds
6-1 SECTION 6 NOMENCLATURE AND STRUCTURE OF ORGANIC COMPOUNDS Many organic compounds have common names which have arisen historically, or have been given to them when the compound has been isolated from a natural product or first synthesised. As there are so many organic compounds chemists have developed rules for naming a compound systematically, so that it structure can be deduced from its name. This section introduces this systematic nomenclature, and the ways the structure of organic compounds can be depicted more simply than by full Lewis structures. The language is based on Latin, Greek and German in addition to English, so a classical education is beneficial for chemists! Greek and Latin prefixes play an important role in nomenclature: Greek Latin ½ hemi semi 1 mono uni 1½ sesqui 2 di bi 3 tri ter 4 tetra quadri 5 penta quinque 6 hexa sexi 7 hepta septi 8 octa octo 9 ennea nona 10 deca deci Organic compounds: Compounds containing the element carbon [e.g. methane, butanol]. (CO, CO2 and carbonates are classified as inorganic.) See page 1-4. Special characteristics of many organic compounds are chains or rings of carbon atoms bonded together, which provides the basis for naming, and the presence of many carbon- hydrogen bonds. The valency of carbon in organic compounds is 4. Hydrocarbons: Compounds containing only the elements C and H. Straight chain hydrocarbons are named according to the number of carbon atoms: CH4, methane; C2H6 or H3C-CH3, ethane; C3H8 or H3C-CH2-CH3, propane; C4H10 or H3C-CH2- CH2-CH3, butane; C5H12 or CH3CH2CH2CH2CH3, pentane; C6H14 or CH3(CH2)4CH3, hexane; C7H16, heptane; C8H18, octane; C9H20, nonane; C10H22, CH3(CH2)8CH3, decane. -
Comparative Responses of Rice (Oryza Sativa) Straw to Urea Supplementation and Urea Treatment
COMPARATIVE RESPONSES OF RICE (ORYZA SATIVA) STRAW TO UREA SUPPLEMENTATION AND UREA TREATMENT M. N. A. Kumar1, K. Sundareshan, E. G. Jagannath S. R. Sampath and P. T. Doyle2 Southern Regional Station, National Dairy Research Institute, Bangalore - 560030, India Summary Twenty five 75% Holstein Friesian cross bred bullocks fed rice straw (Oryza saliva) of long form, were fed with the following five treatments. 1. Rice straw, untreated (RS) 2. RS + water (1:1), stored for 24 hours (WRS) 3. RS (100 kg) + urea solution (4 kg urea/100 litre water) and dried (USRS) 4. RS (100 kg) + urea solution (as in 3) stored in wet condition for 24 hours (UWRS) 5. RS (100 kg) + urea solution (as in 3) stored in pit for 21 days (UTRS). Potential digestibility of treatments of RS was evaluated by monitoring (in vitro) Simulating Rumen like Fermentation (SRLF). The results indicated that Dry Matter Intake (DMI), digestibility of nutrients, N utilization were of the order UTRS > UWRS > USRS > WRS and RS (p < 0.05 to P < 0.01). SRLF index was high (255.84) for UTRS and least (145.58) for USRS. It was interm ediary (199.66) for UWRS. The acetyl content (AC) of UTRS with higher hemicellulose (HCE) dig estibility (80.8%) was low compared to UWRS, USRS, RS and WRS. The acetate content was of the order UTRS < UWRS < USRS < WRS and RS thereby indicating that reduction in acetyl con tent was an index of positive response of urea-treatment of RS. In addition, the ratio of HCE/AC in faeces of UTRS was 0.87 as against the ratios (2.26-2.48) observed in other treatments recording reduction jn AC due to urea-treatinent. -
Molecular Structure of Wlbb, a Bacterial N-Acetyltransferase Involved in the Biosynthesis †,‡ of 2,3-Diacetamido-2,3-Dideoxy-D-Mannuronic Acid James B
4644 Biochemistry 2010, 49, 4644–4653 DOI: 10.1021/bi1005738 Molecular Structure of WlbB, a Bacterial N-Acetyltransferase Involved in the Biosynthesis †,‡ of 2,3-Diacetamido-2,3-dideoxy-D-mannuronic Acid James B. Thoden and Hazel M. Holden* Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706 Received April 14, 2010; Revised Manuscript Received April 29, 2010 ABSTRACT: The pathogenic bacteria Pseudomonas aeruginosa and Bordetella pertussis contain in their outer membranes the rare sugar 2,3-diacetamido-2,3-dideoxy-D-mannuronic acid. Five enzymes are required for the biosynthesis of this sugar starting from UDP-N-acetylglucosamine. One of these, referred to as WlbB, is an N-acetyltransferase that converts UDP-2-acetamido-3-amino-2,3-dideoxy-D-glucuronic acid (UDP- GlcNAc3NA) to UDP-2,3-diacetamido-2,3-dideoxy-D-glucuronic acid (UDP-GlcNAc3NAcA). Here we report the three-dimensional structure of WlbB from Bordetella petrii. For this analysis, two ternary structures were determined to 1.43 A˚resolution: one in which the protein was complexed with acetyl-CoA and UDP and the second in which the protein contained bound CoA and UDP-GlcNAc3NA. WlbB adopts a trimeric quaternary structure and belongs to the LβH superfamily of N-acyltransferases. Each subunit contains 27 β-strands, 23 of which form the canonical left-handed β-helix. There are only two hydrogen bonds that occur between the protein and the GlcNAc3NA moiety, one between Oδ1 of Asn 84 and the sugar C-30 amino group and the second between the backbone amide group of Arg 94 and the sugar C-50 carboxylate. -
215-216 HH W12-Notes-Ch 15
Chem 215 F12 Notes Notes – Dr. Masato Koreeda - Page 1 of 17. Date: October 5, 2012 Chapter 15: Carboxylic Acids and Their Derivatives and 21.3 B, C/21.5 A “Acyl-Transfer Reactions” I. Introduction Examples: note: R could be "H" R Z R O H R O R' ester O carboxylic acid O O an acyl group bonded to R X R S acid halide* R' an electronegative atom (Z) thioester O X = halogen O R' R, R', R": alkyl, alkenyl, alkynyl, R O R' R N or aryl group R" amide O O O acid anhydride one of or both of R' and R" * acid halides could be "H" R F R Cl R Br R I O O O O acid fluoride acid chloride acid bromide acid iodide R Z sp2 hybridized; trigonal planar making it relatively "uncrowded" O The electronegative O atom polarizes the C=O group, making the C=O carbon "electrophilic." Resonance contribution by Z δ * R Z R Z R Z R Z C C C C O O O δ O hybrid structure The basicity and size of Z determine how much this resonance structure contributes to the hybrid. * The more basic Z is, the more it donates its electron pair, and the more resonance structure * contributes to the hybrid. similar basicity O R' Cl OH OR' NR'R" Trends in basicity: O weakest increasing basiciy strongest base base Check the pKa values of the conjugate acids of these bases. Chem 215 F12 Notes Notes –Dr. Masato Koreeda - Page 2 of 17. -
Chemicals Required for the Illicit Manufacture of Drugs Table 1 SUBSTANCES in TABLES I and II of the 1988 CONVENTION
Chemicals Required 1. A variety of chemicals are used in the illicit manufacture of for the Illicit drugs. The United Nations Convention against Illicit Traffic in Manufacture of Drugs Narcotic Drugs and Psychotropic Substances of 1988 (1988 Convention) refers to “substances frequently used in the illicit manufacture of narcotic drugs and psychotropic substances”. Twenty-two such substances are listed in Tables I and II of the 1988 Convention as in force on 1st May, 1998. (See Table1) Table 1 Table I Table II SUBSTANCES IN N-Acetylanthranilic acid. Acetic anhydride TABLES I AND II OF Ephedrine Acetone THE 1988 Ergometrine Anthranilic acid CONVENTION Ergotamine Ethyl ether Isosafrole Hydrochloric acid* Lysergic acid Methyl ethyl ketone 3,4-methylenedioxyphenyl-2-propanone Phenylacetic acid 1-phenyl-2-propanone Piperidine Piperonal Potassium permanganate Pseudoephedrine Sulphuric acid* Safrole Toluene The salts of the substances in this Table The salts of the substances whenever the existence of such salts is in this Table whenever the possible. existence of such salts is possible. * The salts of hydrochloric acid and sulphuric acid are specifically excluded from Table II. U N D C P 11 The term “precursor” is used to indicate any of these substances in the two Tables. Chemicals used in the illicit manufacture of narcotic drugs and psychotropic substances are often described as precursors or essential chemicals, and these include true precursors, solvents, oxidising agents and other Chemicals used in the illicit manufacture of narcotic substances. Although the term is not drugs and psychotropic substances are often technically correct, it has become common described as precursors or essential chemicals, and practice to refer to all such substances as these include true precursors, solvents, oxidising “precursors”. -
For Personal Use Only
Antidep ® Dowden Health Media CopyrightFor personal use only Referring to certain groups of drugs as antidepressants does them a great disservice; their potential uses range far beyond mood disorders For mass reproduction, content licensing and permissions contact Dowden Health Media. ressants molecule is a molecule is a molecule—until it The spectrum becomes identified with a purpose. Consider, for example, (-)-trans-4R-(4’-fluorophenyl)-3S- beyond depression A[(3’,4’-methylenedioxyphenoxy) methyl] piperidine. You probably know this molecule as paroxetine—an an- tidepressant, of course, but it is more than that. If you James W. Jefferson, MD examine paroxetine’s FDA-approved indications, it also Distinguished senior scientist has anti-panic, anti-social anxiety, anti-obsessive-com- Madison Institute of Medicine, Inc. pulsive disorder, anti-posttraumatic stress disorder, and Clinical professor of psychiatry University of Wisconsin School of Medicine anti-premenstrual dysphoric disorder effects. and Public Health “Antidepressants” have achieved fame as antidepres- sants; one could say these molecules’ search for meaning has been fulfilled. Yet even within psychiatry, their many other uses (Table, page 36) can create semantic misunder- standings. Beyond psychiatry, consider the nondepressed patient with neurocardiogenic syncope who wonders why he’s being treated with an antidepressant. Rather than calling antidepressants “panaceas,” the better choice is to educate patients about the drugs’ wide spectrum of activity. Let’s look broadly across the so-called antidepressants and examine their varied uses in psychiatry and other medical specialties. Pain syndromes Peripheral neuropathy. The only antidepressant with an FDA-approved pain indication is duloxetine, Current Psychiatry © 2007 MATT MANLEY Vol. -
Safety Data Sheet: Piperidine
Safety data sheet according to Regulation (EC) No. 1907/2006 (REACH), amended by 2015/830/EU Piperidine PEPTIPURE® ≥99,5 %, for peptide synthesis article number: A122 date of compilation: 2016-11-25 Version: 2.0 en Revision: 2020-07-20 Replaces version of: 2016-11-25 Version: (1) SECTION 1: Identification of the substance/mixture and of the company/ undertaking 1.1 Product identifier Identification of the substance Piperidine Article number A122 Registration number (REACH) 01-2119962908-20-xxxx Index No 613-027-00-3 EC number 203-813-0 CAS number 110-89-4 1.2 Relevant identified uses of the substance or mixture and uses advised against Identified uses: laboratory chemical laboratory and analytical use 1.3 Details of the supplier of the safety data sheet Carl Roth GmbH + Co KG Schoemperlenstr. 3-5 D-76185 Karlsruhe Germany Telephone: +49 (0) 721 - 56 06 0 Telefax: +49 (0) 721 - 56 06 149 e-mail: [email protected] Website: www.carlroth.de Competent person responsible for the safety data : Department Health, Safety and Environment sheet: e-mail (competent person): [email protected] 1.4 Emergency telephone number Name Street Postal code/ Telephone Website city National Poisons Inform- Beaumont Road Dublin 9 01 809 2166 https://www.poisons.ie/ ation Centre Beaumont Hospital SECTION 2: Hazards identification 2.1 Classification of the substance or mixture Classification according to Regulation (EC) No 1272/2008 (CLP) Classification acc. to GHS Section Hazard class Hazard class and cat- Hazard egory state- ment 2.6 flammable liquid (Flam. Liq. 2) H225 3.1O acute toxicity (oral) (Acute Tox. -
Dissociation Constants of Organic Acids and Bases
DISSOCIATION CONSTANTS OF ORGANIC ACIDS AND BASES This table lists the dissociation (ionization) constants of over pKa + pKb = pKwater = 14.00 (at 25°C) 1070 organic acids, bases, and amphoteric compounds. All data apply to dilute aqueous solutions and are presented as values of Compounds are listed by molecular formula in Hill order. pKa, which is defined as the negative of the logarithm of the equi- librium constant K for the reaction a References HA H+ + A- 1. Perrin, D. D., Dissociation Constants of Organic Bases in Aqueous i.e., Solution, Butterworths, London, 1965; Supplement, 1972. 2. Serjeant, E. P., and Dempsey, B., Ionization Constants of Organic Acids + - Ka = [H ][A ]/[HA] in Aqueous Solution, Pergamon, Oxford, 1979. 3. Albert, A., “Ionization Constants of Heterocyclic Substances”, in where [H+], etc. represent the concentrations of the respective Katritzky, A. R., Ed., Physical Methods in Heterocyclic Chemistry, - species in mol/L. It follows that pKa = pH + log[HA] – log[A ], so Academic Press, New York, 1963. 4. Sober, H.A., Ed., CRC Handbook of Biochemistry, CRC Press, Boca that a solution with 50% dissociation has pH equal to the pKa of the acid. Raton, FL, 1968. 5. Perrin, D. D., Dempsey, B., and Serjeant, E. P., pK Prediction for Data for bases are presented as pK values for the conjugate acid, a a Organic Acids and Bases, Chapman and Hall, London, 1981. i.e., for the reaction 6. Albert, A., and Serjeant, E. P., The Determination of Ionization + + Constants, Third Edition, Chapman and Hall, London, 1984. BH H + B 7. Budavari, S., Ed., The Merck Index, Twelth Edition, Merck & Co., Whitehouse Station, NJ, 1996.