DOCSLIB.ORG

June, 1949 the SCHMIDT REACTION

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
June, 1949 the SCHMIDT REACTION June, 1949 THESCHMIDT REACTION WITH ALIPHATICACIDS 2233 thiamine hydrobromide was 200 mg. (73% based on py- Stability of Neopyrithiamine Salts in Solution.-The rimidine); m. p. 205-210" (dec.); Amax. in water 238 and ultraviolet absorption spectrum of a freshly prepared 270 mp. methanolic solution of neopyrithiamine hydrobromide Anal. Calcd. for Cl4HdT4OBre: C, 40.02; H, 4.80; changed when the solution was allowed to stand for several N, 13.34. Found: C, 39.70; H, 5.02; N, 12.99. days at room temperature. The 235 mp band shifted +o 240 mp and had a lower intensity, while the 273 mp band Reparation of Neopyrithiamine Hydrobromide in Ace- shifted to 267 mp and was of greater intensity. At the tone.-% hundred milligrams of 2-methyl-3-( 8-hy- same time the minimum point of the curve at 252 mp droxyethyl) -pyridine was dissolved in 10 ml. of acetone, changed to 250 mp and was of much greater intensity. In and to this solution was added 240 mg. of 2-methyl-5- short, the two bands seemed to coalesce and to resemble bromomethyl-6-aminopyrimidine dihydrobromide. The that of pyrithiamine (hydrobromide). mixture was shaken until most of the pyrimidine had dis- The decomposition was only slight in aqueous solution solved. In a few minutes a gummy precipitate had at room temperature. When the temperature was in- formed. The supernatant liquor was decanted from the creased, however, the decomposition was much more rapid. gum and was allowed to stand overnight at room tempera- In neutral or alkaline solutions, the decomposition was ture. The product separated from solution as a solid. rapid even at room temperature. Under these conditions It was centrifuged, washed with fresh portions of acetone the 235 mp band completely disappeared. and with petroleum ether, and dried. The yield of neo- Both neopyrithiamine hydrobromide and neopyrithi- pyrithiamine hydrobromide was 150 mg. (55% based on amine hydrochloride can lose hydrogen bromide or hydro- pyrimidine); m. p., 218-220" (dec.); XmI. in water, 238 gen chloride when heated under reduced pressure. The and 271 mp. loss was greater with longer heating and with higher Anal. Calcd. for Cl4HreN4OBr?: C, 40.02; H, 4.80; temperatures. Conversely, some samples crystallized from N, 13.34. Found: C, 40.36; H, 5.09; N, 12.92. solution with varying amounts of hydrogen bromide or Preparation of Neopyrithiamine Picrate.-One hundred hydrogen chloride. milligrams of neop yrithiamine hydrobromide was dissolved in 20 ml. of water and added to a solution of 200 mg. of Acknowledgments.-The authors wish to ex- picric acid in 50 ml. of water. The solution was filtered press their appreciation and thanks to Dr. Nelson from a small amount of gummy precipitate and was al- R. Trenner and Dr. Charles Rosenblum for their lowed to stand overnight in the refrigerator where the helpful suggestions on this problem, and for de- product separated in a crystalline condition. The prod- uct was filtered, washed with water and dried. The termining and interpreting the physical meas- yield of neopyrithiamine picrate was 70 mg. (40%); urements reported in this paper. The authors m. p. 186-188". also wish to thank Mr. R. N. Boos and his Anal. Calcd. for C~~HI,N~OOI~:C, 43.58; H, 3.38; associates for the microanalyses. N, 19.55. Found: C, 43.52; H, 3.28; N, 19.61. Preparation of Neopyrithiamine Hydrochloride .-Eight Summary hundred and forty milligrams of neopyrithimine hydro- bromide was converted into the picrate as described The previously reported method of preparation above. The melting point of a dried sample was 183- of 1-[ (4-amino-2-methyl)d-pyrimidylmethyl]-2- 184". The main crop was suspended in water, was acidi- methyl-3- ( 8-hydroxyethyl) -pyridinium bromide fied with dilute hydrochloric acid, and was extracted with nitrobenzene to remove the liberated picric acid. The hydrobromide was found to yield a substance that aqueous solution was extracted further with ether, and was not analytically in agreement with the de- then concentrated to a small volume under reduced pres- sired product. This product has been prepared sure and at a low temperature. On addition of isopropyl alcohol to the residue, the product crystallized slowly. It now, and its analytical and physical properties was filtered, washed with isopropyl alcohol, washed with are described. It has been named neopyrithi- ether and dried. The yield of neopyrithiamine hydro- amine hydrobromide. Neopyrithiamine hydro- chlorid' was 260 mg. (40% from the bromide); m. p. bromide has been converted first into the picrate 234-236' (dec.) ; Amsx. in water 235 and 273 mp. and then into the hydrochloride. Anal. Calcd. for CI~HIBN~OCIZ:C, 50.76; H, 6.09; N, 16.92. Found: C, 50.69; H, 6.08; N, 16.76. RAHWAY,N. J. RECEIVEDFEBRUARY 10, 1949 [CONTRIBUTION FROM THE DEPARTMENTOF CHEMISTRY, MASSACHUSETTSINSTITUTE OF TECHNOLOGY] The Schmidt Reaction. I. Conditions and Reaction Mechanism with Primary, Secondary and Tertiary Aliphatic Acids BY CONRADSCHUERCH, JR.,~J AND ERNESTH. HUNTRESS Although carboxylic acids react with sulfuric on the behavior of the lower primary, secondary and hydrazoic acids to give primary amines, a and tertiary representatives, and that for the last recent reviewa indicates only meager information group high yields of amine have been obtained (1) This paper is constkted from part of a dissertation submitted only with acids containing a cyclopentyl radical by Conrad Schuerch, Jr., to the Faculty of the Massachusetts In- adjacent to the carboxyl. The influence of re- stitute of Technology in June, 1947, in partial fulfillment of the re- action conditions upon yield of amine has been quirements for the degree of Doctor of Philosophy. , It was presented before the Division of Organic Chemistry at the 112th meeting of the inadequately characterized, and whether yields A. C. S. in New York on September 18, 1947. less than theoretical were due to incomplete (2) Present address: Division of Cellulose and Industrial Chemis- reaction or to diversion into side reactions has try, McGill University, Montreal 2, Canada. (3) Wolff, "The Schmidt Reaction, Organic Reactions," Vol. 3, rarely been established. The present study adds John Wiley and Sons, New York, N. Y., 1946, pp. 307-336. to our knowledge of acetic, isobutyric and tri- 2234 CONRADSCHWERCH, JR., AND ERNESTH. HUNTRESS Vol. 71 methylacetic acids, and reports new observations amine and some isopropyl alcohol. When tri- on the reaction products both from these and other methylacetic acid was allowed to react with secondary and tertiary acids. sodium azide (1.17 moles), some unchanged acid The conditions necessary for complete con- was recovered, and the reaction products were version of the acids were determined by allowing acetone, methylamine, ammonia, carbon dioxide, a small quantity of organic acid to react with carbon monoxide and 3370 of t-butylamine. By sulfuric acid and sodium azide according to diluting the reaction mixture with nitromethane, Oesterlin’s modification4 of the original procedure the formation of carbon monoxide was completely and analyzing the evolved gas for carbon dioxide. inhibited, and the yield of t-butylamine was From the latter simple calculation gave the raised to 55%, but the cleavage products were amount of carboxylic acid reacting, while direct still formed. azide decomposition5 was measured by nitrogen Dimethylethylacetic acid reacted similarly, found in excess of that required for the reaction forming a larger proportion of carbon monoxide, RCOOH 4- HN,+RNHz + COz + Nz. less t-alkylamine (somewhat impure), acetone, These experiments have shown that a molal ethyl methyl ketone, ammonia, methylamine and ratio of sulfuric acid to organic acid of about 7 impure ethylamine. The reaction of l-methyl- or 9 : 1 is usually required for complete reaction, cyclohexanecarboxylic acid produced both carbon and that neither trichloroacetic nor phosphoric monoxide and carbon dioxide and a 42% yield of acids can be used in place of sulfuric acid. It was 1-methylcyclohexylamine, but the expected cleav- confirmed that hydroxylic solvents interfere with age products were not found. An investigation the reaction but that nitromethane, a solvent of other tertiary acids showed that the propor- which does not ionize in sulfuric acid,6a was a tion of carbon monoxide increased as the chain satisfactory diluent.’ Acetic anhydride was length of the acid increased, and with triethyl- found to react somewhat more completely than acetic acid (to be reported later), the proportion acetic acid under the same conditions, but chloro- of carbon monoxide was found to be greater at the acetic and trichloroacetic acids did not give off beginning of the reaction than at the end. carbon dioxide under ordinary conditions. These No method was found for decreasing the amount results can all be explained adequately by the ionic of cleavage products formed when carbon dioxide mechanism proposed for this reaction by other alone was evolved. Under these conditions, the ~orkers,~~~~~~~~~and indicate the importance of proportion of cleavage products to t-alkylamine maintaining the organic acid in the form of a did not appear to be sensitive to dilution of the positive ion for complete reaction. reaction medium. A temperature higher than the usual 40’ was In explanation of these results, these equations found to be necessary only in the case of acetic are proposed as a tentative mechanism acid. At 60°, good yields of carbon dioxide and methylamine were obtained ; at lower temperature No HzSO4 w304 p+ there was excessive direct azide decomposition. l2 R-C-011 7R-C(OH)z+ 7R-C Most other variables were of minor significance. HSO4- HSOd- + HaO+ Preparative experiments showed that only I I11 acetic acid gave equivalent amounts of carbon dioxide and amine. Isobutyric acid gave quanti- tative yields of carbon dioxide, S4yo of isopropyl- (4) Oesterlin, Z.
Load more

Recommended publications
  • Beckmann Rearrangement of Ketoxime Catalyzed by N-Methyl-Imidazolium Hydrosulfate
    molecules Article Beckmann Rearrangement of Ketoxime Catalyzed by N-methyl-imidazolium Hydrosulfate Hongyu Hu †, Xuting Cai †, Zhuying Xu, Xiaoyang Yan * and Shengxian Zhao * Xingzhi College, Zhejiang Normal University, Jinhua 321004, China; [email protected] (H.H.); [email protected] (X.C.); [email protected] (Z.X.) * Correspondence: [email protected] (X.Y.); [email protected] (S.Z.); Tel./Fax: +86-579-8229-1129 (X.Y. & S.Z.) † These authors contributed equally to this work. Received: 7 June 2018; Accepted: 14 July 2018; Published: 18 July 2018 Abstract: Beckmann rearrangement of ketoxime catalyzed by acidic ionic liquid-N-methyl- imidazolium hydrosulfate was studied. Rearrangement of benzophenone oxime gave the desirable ◦ product with 45% yield at 90 C. When co-catalyst P2O5 was added, the yield could be improved to 91%. The catalyst could be reused three cycles with the same efficiency. Finally, reactions of other ketoximes were also investigated. Keywords: Beckmann rearrangement; ketoxime; acidic ionic liquid; catalysis 1. Introduction Over the past years, amide derivatives have received much attention owing to their broad range of applications in many fields such as the pharmaceutical industry, chemical biology, the agrochemical industry, engineering plastics, and so on [1–6]. Various approaches have been developed for the synthesis of amide compounds including nucleophilic acyl substitution reactions with amines [7], Staudinger ligation [8], Schmidt reaction [9] and Beckmann rearrangement [10]. However, generations of large amounts of undesired by-products and corrosive phenomenon associated with common acid (H2SO4 and SOCl2) based on liquid phase protocols provide a challenging task for chemists to develop alternative methods [11,12].
    [Show full text]
  • Molecular REARRANGEMENTS
    Key words: rearrangement reactions, migration to electron deficient nitrogen, electron deficient oxygen, electron deficient carbon. Migratory aptitude, cross- over experiments Rearrangment reactions are an interesting class of reactions wherein a group or an atom migration during the course of the reaction. While most of the rearrangements are designed in that fashion, it can also be undesirable in some cases. Depending on the reaction conditions, the nature of rearrangement (and the product) could also change. In this module, various rearrangement reactions are presented. These are classified with respect the the migration origin and migration terminus. Emphasis has been placed on examples involving skeletal rearrangements that are practically used in day-to-day organic synthesis. Rearrangement reactions involve the migration of a group or an atom from one center (migration origin) to another (migration terminus) within the same molecule. W W A B A B In the above-mentioned generalized representation, atom-A is migration origin from where the migrating group “W” moves to atom-B (migration terminus) These rearrangements can be roughly classified on the basis of the nature of the migrating group/atom, i.Nucleophilic or Anionotropic: migrating group migrates with its electron pair. ii.Electrophilic or cationotropic: migrating group migrates without its electron pair. iii.Free radical: migrating group migrates with only one electron. Of these most commonly found are nucleophilic one. These rearrangements can take place in two possible modes, i.Intramolecular : In these migrating group do not completely detach from the migration origin and occurs within the same molecule. W A B A B W ii. Intermolecular : In these migrating group is detached from the migration origin.
    [Show full text]
  • The Chemical Synthesis of the Crinine and Haemanthamine
    molecules Review The Chemical Synthesis of the Crinine and Haemanthamine Alkaloids: Biologically Active and Enantiomerically-Related Systems that Serve as Vehicles for Showcasing New Methodologies for Molecular Assembly † Nan Hu, Lorenzo V. White, Ping Lan and Martin G. Banwell * Institute for Advanced and Applied Chemical Synthesis, Jinan University, Zhuhai 519070, China; [email protected] (N.H.); [email protected] (L.V.W.); [email protected] (P.L.) * Correspondence: [email protected] † Dedicated to the memory of our friend and colleague Professor Lew Mander FAA, FRS (1939–2020). Abstract: The title alkaloids, often referred to collectively as crinines, are a prominent group of structurally distinct natural products with additional members being reported on a regular basis. As such, and because of their often notable biological properties, they have attracted attention as synthetic targets since the mid-1950s. Such efforts continue unabated and more recent studies on these alkaloids have focused on using them as vehicles for showcasing the utility of new synthetic methods. This review provides a comprehensive survey of the nearly seventy-year history of these Citation: Hu, N.; White, L.V.; Lan, P.; synthetic endeavors. Banwell, M.G. The Chemical Synthesis of the Crinine and Keywords: alkaloid; crinine; haemanthamine Haemanthamine Alkaloids: Biologically Active and Enantiomerically-Related Systems that Serve as Vehicles for Showcasing 1. Introduction New Methodologies for Molecular The alkaloids isolated from the widely distributed herbaceous and bulbous flowering Assembly . Molecules 2021, 26, 765. plants of the amaryllis (Amaryllidaceae) family number more than five hundred and about https://doi.org/10.3390/molecules 10% of these embody the 2,3,4,4a-tetrahydro-1H,6H-5,10b-ethanophenanthridine ring sys- 26030765 tem (Figure1)[ 1].
    [Show full text]
  • Keyphrase Definitions
    DEFINITIONS OF SPORE KEYPHRASES (RXN_TYPE'S) GENERAL RULES AND DEFINITIONS: GENERAL RULE 1: In reactions with more than one reactant, corresponding keyphrases often apply to the two coupling partners (e.g. "N-alkylation" for Reactant 1, "amination" for Reactant 2). As a general rule, appropriate keyphrases are assigned to all reactants of a given reaction, regardless of the size of the particular compound. GENERAL RULE 2: Keyphrases are assigned to the actual reactant-to-product conversion; the transformations of the likely intermediates of the reaction mechanism (as opposed to intermediates of a multi-step reaction) are usually not taken into account. GENERAL RULE 3: Keyphrases are only assigned to transformations of the reactants of a reaction, and not to transformations of catalysts or reagents. However, the transformation that a reagent effects is of course considered. Thus, in a reaction R-CO-Cl (+ reagent NH3) -> R-CO-NH2 the keyphrase "amidation", induced by the reagent ammonia, is assigned while the keyphrases "N-acylation" is not, since the compound undergoing N-acylation is only a reagent. Note to the Keyphrases in Chapter C: Apart from chapter C8 (Ring Systems), all but four of the keyphrases apply to reactions leading to either cyclic or acyclic products (thus, both open-chain ester formations and lactonizations will have the keyphrase "esterification"). These four exceptions are the "...-alkylation", terms (C- /N-/O-/S-alkylation), which are only used for the formation of open-chain C-C, C-N, C-O or C-S bonds (otherwise, all cycloadditions and many heterocyclic syntheses would formally have to be regarded as "C/N/O/S-alkylation").
    [Show full text]
  • Organic Cumulative Exam April 1998
    Organic Cumulative Exam April 1998 The Schmidt Reaction There are actually several related reactions in organic chemistry that have been given the moniker "The Schmidt Reaction" or "Schmidt Rearrangement". We'll look at a couple of them here. 1. The Schmidt Reaction of carboxylic acids involves in the conversion of an acid to an amine. Show the reagents used to effect this transformation and suggest a mechanism for the reaction. (10pts) 2. In an effort to trim down the amount of chemistry that students learn, many undergraduate textbooks no longer include the Schmidt Reaction. Most do include, however, the closely related Hofmann Rearrangement. Show a Hofmann rearrangement. (6pts) 3. Ureas are common side products formed in the Schmidt and Hofmann reactions described above. For example, when butanamide is subjected to these Hofmann reaction conditions, N,N-dipropylurea is isolated along with the desired product. Suggest how this urea forms. (6 pts) 4. What did the experiments shown below tell early researchers about the mechanism of the Schmidt and Hofmann rearrangements? (What alternate mechanism(s) do these observations rule out?) (6 pts) 13 13 CH3 CH2CONH2 Hofmann CH3 CH2NH2 15 15 CH3CH2CO NH2 CH3CH2 NH2 H Schmidt H COOH NH2 Ph Ph CONH2 Hofmann NH2 (occurs with the ease of a "normal" Hofmann rxn) 5. Now for a different Schmidt reaction: the Schmidt reaction of ketones. The major product resulting from addition of hydrazoic acid to cyclohexanone is shown below. Suggest a mechanism for this Schmidt Reaction. (7pts) O O HN3 HCl NH 6. A Schmidt Reaction utilizing ALKYL azides has recently been developed independently by Aube and Pearson.
    [Show full text]
  • The Design and Synthesis of Complexes for the Activation of Carbon Dioxide
    The Design and Synthesis of Complexes for the Activation of Carbon Dioxide A Thesis Presented by Rafael Bou Moreno In Partial Fulfilment of The Requirements For The Award of The Degree of Doctor of Philosophy Of University College London University College London Department of Chemistry 20 Gordon Street London WC1H 0AJ Declaration I, Rafael Bou Moreno 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. PhD Thesis Rafael Bou-Moreno ACKNOWLEDGMENTS I would like to thank the person who made possible the production of this work and this thesis, which has been my mentor, source of inspiration, enthusiasm, extremely supportive and intelligent, as well as a friend; who not only thought me how to look at chemistry in a different way, but also valuables lessons in life: Professor James C. Anderson. I would also like to thank all the past and present members of the Anderson group who have been a source of inspiration, learning and very good friends: Warren, Helen C., Helen G., Liz, Greg, Michelle, Matt, Lisa, Adam, György, Rob, Jon, Paul and Andreas. Specially those who shared the “London Adventure”. Throughout my studies we have got financial support from BPF, The University of Nottingham and University College London, to whom we are very grateful. In the same way I would like to thank the technical staff at both universities for their constant help. Finally I would like to thank my parents and my sister who have been so far away, yet so supportive and always believed in me.
    [Show full text]
  • THE APPLICATION of the SCHMIDT REACTION to the PREPARATION of CERTAIN W-Ar.UNO ACIDS and DIAMINES
    THE APPLICATION OF THE SC IDT REACTION TO THE PREPARATION OF CERTAIN W..AMINO ACIDS AND DI INES by RAYMOND EDWARD PARSONS A THESIS submitted to OREDON STATE COLLIDE in partial tulfil~ent of the requirements for the degree of MASTER OF SCIENCE June 1956 'r* tPtR09Dl Redacted for Privacy hofuror of Ghcairtttr In Cbengr of, lrJor \,' Redacted for Privacy Gbr$urn -of DcpmFcnt of 0borl,rtry Redacted for Privacy Chrlrurn Eobool Oli&rtt Omtttar Redacted for Privacy D.rn of Grrdurtc School Drtc thcrlr la prcaonf,r ACKNO\VLEDG1t1ENT 'rhe author wishes to express his appreciation to Dr. Bert E. Christensen for his guidance and encouragement throughout the course of this xtesearch. TABLE OF CONTENTS .Page INTRODUCTION .• ·• •• •• • • • •• . ..·. • • •• • • •• • l EXPERIMENTAL ·• .• • • • •• . •· ... • • .. • •• • • • 13 SUM.MARY •. • •• • • •. • • • • • •. • • • •. • • • • • 25 BIBLIOGRAPHY ·• ·• • .. .. • • ·• ·• ·•· • • ·• • • • • • • ·• 27 LIST OF TABLES I The Schmidt Reaction with Aliphatic Diearboxylio Acids. -. • • • • • • • • • • • • 15 II A Comparison of the Percent of Hydrazoic Acid Reacting in the Schmidt Reaction Based Upon the Isol ated Yield and the Carbon Dioxide Adsorbed • • • • , • • • • • • • • • 22 III The Schmidt Reac tion with Certain Heterocy clic Compounds . • • • • • • • • • • • 23 IV Results of Chloride Anal ys.is••••• . " 23 THE APPLICATION OF THE SCHMIDT REACTION TO THE PREPARATION OF CERTAIN w-Ar.UNO ACIDS AND DIAMINES INTRODUCTION The reaction between hydrazoio acid and carbonyl compounds in the presence of strong mineral acids is known as the Schmidt reaction. 0 II RCOH + HN3 H2S04 ) RNH2 + COg + N2 0 II RCH + HN3 H~04 ) RON + HgO + N2 0 0 Il II RCR + HN3 H2S04 ) RCNHR + N2 It was discovered by Karl Friedrich Schmidt in 1923 in a , study of the decomposition ot hydrazoic acid by sulfuric acid (26,p.Sll).
    [Show full text]
  • Synthesis and Biological Importance of Amide Analogues
    REVIEW ARTICLE Synthesis and biological importance of amide analogues Preeti Rajput, Abhilekha Sharma* Rajput P, Sharma A. Synthesis and biological importance of amide amide linage containing compounds. The main purpose of article is to analogues. J Pharmacol Med Chem 2018;2(1):22-31. provide information on the development of novel amide derivatives to the scientific community. Doing so, it focuses on mechanisms of action and ABSTRACT adverse events, and suggests measures to be implemented in the clinical The present research article deals with the amide analogues prepared by practice according to bioethical principles. available very well-known name reactions. The author have studied the name reactions like Beckmann rearrangement, Schmidt reaction, Passerine reaction, Key Words: Novel amide derivatives; Amide analogues; Amide formation Willgerodt–Kindler reaction and UGI reaction, which involves preparation of routes starting from substrates other than carboxylic acids and their T he Amide bond formation reactions are among the most important derivatives (5). Thus, with the help of transition metals, a plethora of transformations in organic chemistry and biochemistry because of the functional groups, such as nitriles, aldehydes, ketones, oximes, primary widespread occurrence of amides in pharmaceuticals, natural products alcohols or amines, can be now conveniently employed as starting and biologically active compounds. The amide group is widely present in materials for the construction of the amide bond. There are three types of the drugs, intermediates, pharmaceuticals, and natural products. It is also amides available in Chemistry: (i) an organic amide which is also referred available in large number of industrial materials including polymers, as carboxamide, (ii) a sulfonamide, and (iii) a phosphoramide.
    [Show full text]
  • Intramolecular Schmidt Reaction: Applications in Natural Product Synthesis
    HOT TOPICS: MULTIFUNCTIONAL MATERIALS AND ORGANIC SYNTHESIS 276 CHIMIA 2006, 60, No. 5 Chimia 60 (2006) 276–284 © Schweizerische Chemische Gesellschaft ISSN 0009–4293 Intramolecular Schmidt Reaction: Applications in Natural Product Synthesis Erich Nyfeler and Philippe Renaud* Abstract: The intramolecular Schmidt reaction was first described at the beginning of the 1990s and rapidly proved to be a powerful tool for the fast assembly of complex nitrogen-containing heterocycles. This review focuses on the application of this reaction in the synthesis of natural products and other biologically relevant compounds. Keywords: Alkaloids · Alkyl azides · Iminium ions · Lactams · Rearrangement · Tertiary amines · Total synthesis 1. Introduction ment. Cation 1.8a loses water to give the [11]. (+)-Camphoric acid 2.1 reacts with so- iminodiazonium intermediate 1.9, which dium azide in the presence of sulfuric acid The Schmidt reaction describes the reaction undergoes a 1,2 shift of an alkyl group de- to afford diamine 2.2 in 91% yield. of carbonyl compounds, such as carboxylic livering the nitrilium ion 1.10. Trapping of acids, ketone and aldehydes, with hydra- 1.10 by water gives the amide 1.7. In few zoic acid under protic conditions resulting cases, a pinacol-like mechanism involving in the insertion of a nitrogen atom in a C–C concerted rearrangement of the tetrahedral bond [1–6]. The reaction is also known as intermediate 1.8b with concomitant loss of the Schmidt rearrangement and is closely nitrogen has also been proposed [9][10]. related to the Hofmann and the Curtius re- A recent application of the carboxylic arrangements [7].
    [Show full text]
  • Practical One-Pot Amidation of N-Alloc-, N-Boc-, and N-Cbz Protected Amines Under Mild Cite This: RSC Adv.,2021,11, 15890 Conditions†
    RSC Advances PAPER View Article Online View Journal | View Issue Practical one-pot amidation of N-Alloc-, N-Boc-, and N-Cbz protected amines under mild Cite this: RSC Adv.,2021,11, 15890 conditions† Wan Pyo Hong,a Van Hieu Tranbc and Hee-Kwon Kim *bc A facile one-pot synthesis of amides from N-Alloc-, N-Boc-, and N-Cbz-protected amines has been described. The reactions involve the use of isocyanate intermediates, which are generated in situ in the presence of 2-chloropyridine and trifluoromethanesulfonyl anhydride, to react with Grignard reagents to Received 21st March 2021 produce the corresponding amides. Using this reaction protocol, a variety of N-Alloc-, N-Boc-, and N- Accepted 19th April 2021 Cbz-protected aliphatic amines and aryl amines were efficiently converted to amides with high yields. DOI: 10.1039/d1ra02242c This method is highly effective for the synthesis of amides and offers a promising approach for facile rsc.li/rsc-advances amidation. Creative Commons Attribution 3.0 Unported Licence. Introduction butyl-carbamate (Boc-carbamate), and benzyl-carbamate (Cbz- carbamate) are observed in organic synthetic processes,25–28 Amide functional groups are important in nature, as they provide because N-Alloc-, N-Boc-, and N-Cbz-protected amines are easily the main amino acid linkage in peptides and proteins.1,2 In addi- synthesized from various amines using many methods. tion, amide structures have been frequently found in many natural However, preparation of amides from these protected amines products and biologically active compounds.3–7 Moreover, generally requires two reaction steps: removal of the protecting numerous drugs including anticancer agents, antibiotics, anes- group from amines to produce free amines, followed by reactions thetics, and enzyme inhibitors contain an amide bond moiety.8–12 of amines with carboxylic acids.
    [Show full text]
  • 1 Rearrangement Reactions
    1 1 Rearrangement Reactions A rearrangement reaction is a board class of organic reactions in which an atom, ion, group of atoms, or chemical unit migrates from one atom to another atom in the same or different species, resulting in a structural isomer of the origi- nal molecule. Rearrangement reactions mostly involve breaking and/or making C—C, C—O, or C—N bonds. The migration origin is the atom from which the group moves, and the migration terminus is the atom to which it migrates. Baeyer–Villiger Oxidation or Rearrangement The Baeyer–Villiger oxidation is an organic reaction that converts a ketone to an ester or a cyclic ketone to a lactone in the presence of hydrogen peroxide or peroxy acids [1]. The reaction was discovered in 1899 by Adolf von Baeyer and Victor Villiger. It is an intramolecular anionotropic rearrangement where an alkyl group migrates from the carbonyl carbon atom (migration origin) to an electron-deficient oxygen atom (migration terminus). The most electron-rich alkyl group (most substituted carbon) that is able to stabilize a positive charge migrates most readily. The migration order is as follows: > > > > > > Tertiar y alkyl cyclohexyl secondary alkyl phenyl primary alkyl CH3 H. Several new catalysts including organics, inorganics, and enzymes have been developed for this reaction [2–76]. Amine or alkene functional groups are limi- tations, however, because of their easy and undesirable oxidation. O O R3 O H O O O Peroxyacid R R O 2 + 1 R3 OH R1 R2 or H2O2, CH2Cl2 Ester Ketone Applied Organic Chemistry: Reaction Mechanisms and Experimental Procedures in Medicinal Chemistry, First Edition.
    [Show full text]
  • The Kinetics and Mechanism of the Reaction of Hydrazoic Acid With
    This dissertation has been 62-2123 microfilmed exactly as received BEKNDT, Donald Carl, 1935- THE KINETICS AND MECHANISM OF THE REAC­ TION OF HYDRAZOIC ACID WITH SUBSTITUTED NAPHTHOIC ACIDS. The Ohio State University, Ph.D., 1961 Chemistry, organic University Microfilms, Inc., Ann Arbor, Michigan THE KINETICS AND MECHANISM OF THE REACTION' OF HYDRAZOIC ACID WITH SUBSTITUTED NAPHTHOIC ACIDS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Donald Carl Berndt, B. Sc. ****** The Ohio State University 1961 Approved by idviser Department of Chemistry ' ACKNOWLEDGMENTS The author wishes to thank Professor Harold Shechter for his suggestion of this investigation, for his encour­ agement and guidance during the course of this study, and for his aid in the preparation of the manuscript. The author is grateful to the Mershon fellowship fund and the Chemistry Department of The Ohio State University and to the National Science Foundation for fellowship funds. He is also grateful to the members of the staff and fellow graduate students for informa­ tion and for the use of chemicals and apparatus. i i CONTENTS P^ge I, Introduction ............................................................................ 1 Statement of Problem ...................................................... 1 Historical Aspects ........................................................... 3 II. Discussion of Results . ...................................... 12 Kinetic Order
    [Show full text]