Nitriles

5 Key excerpts on "Nitriles"

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  eBook - ePub

  Ullmann's Fine Chemicals

  • (Author)
  • 2014(Publication Date)
  • Wiley-VCH

    (Publisher)

  Nitriles Peter Pollak, Lonza AG, Basel, Switzerland Gérard Romeder, Lonza AG, Basel, Switzerland Ferdinand Hagedorn, Bayer AG, Leverkusen, Federal Republic of Germany Heinz-Peter Gelbke, BASF Aktiengesellschaft, Ludwigshafen, Federal Republic of Germany

  1. Introduction

  Organic compounds containing the – CN group are generically called Nitriles. The term “nitrile” refers to the triply bound nitrogen atom, ≡ N, and not to the carbon atom attached to it; therefore numbering of the aliphatic chain starts with that carbon atom (e.g., 4-chlorobutyronitrile describes the chemical formula ClCH2 CH2 CH2 CN).

  Nitriles R – CN are usually viewed as derivatives of the corresponding acids R – COOH. Consequently, they are also named by changing the ending “ic acid” or “oic acid” to “onitrile” (e.g., glutaric acid → glutaronitrile; dodecanoic acid → dodecanonitrile, propiononitrile, as an exception, is commonly referred to as propionitrile). Another way of naming Nitriles is to state the name of the group R and use the prefix “cyano” or the suffix “cyanide” (e.g., cyanoethane and ethyl cyanide both describe H3 CCH2 CN). Nitriles that are obtained by addition of hydrogen cyanide to ketones or aldehydes and thus have both a hydroxy and a cyano group attached to the same carbon atom are commonly termed cyanohydrins (e.g., acetone cyanohydrin is identical to 2-hydroxy-2-methylpropionitrile). The same nomenclature applies to 3-hydroxypropionitrile which is commonly named ethylene cyanohydrin.

  2. Aliphatic Nitriles

  Aliphatic Nitriles are important starting materials for polymers as well as for the synthesis of e.g., pharmaceuticals and pesticides.

  2.1. Physical Properties

  The carbon – nitrogen bond is extremely polar, which results in Nitriles having a high dipole moment. This large dipole moment leads to intramolecular association; hence, Nitriles have higher boiling points than would be expected from their molecular mass. Most of the lower molecular mass aliphatic Nitriles (up to C13 H27 CN) are liquids at room temperature. Simple Nitriles such as acetonitrile, propionitrile, glycolonitrile, and malononitrile are miscible with water; the latter two having a higher solubility because of the presence of two polar groups. Nitriles with higher molecular mass are sparingly water-soluble. Nitriles are good solvents for both polar and nonpolar solutes. The physical properties of selected Nitriles are listed in Table 1

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  eBook - ePub

  Advances in Organic Synthesis: Volume 14

  • Atta-ur-Rahman(Author)
  • 2021(Publication Date)
  • Bentham Science Publishers

    (Publisher)

  4 ].

  Scheme (1)) Some methods for the preparation of Nitriles: Ammoxidation (A), hydrocyanation (B), Cyanohydrin formation, (C), and Sandmeyer Reaction (D).

  Besides their application in polymers, Nitriles are also present in more than 30 pharmaceuticals, including antidepressants, antidiabetics, and anticancer drugs (Fig.

  1

  ), since they can act as hydrogen acceptors, increase water solubility and shield the drug from oxidative metabolism [5 - 8 ].

  Fig. (1)) Example of Nitrile-containing compounds in clinical use.

  Moreover, the majority of Nitriles are relatively stable and inexpensive compounds that support a high variation of substituents and can be converted into many functional groups (Scheme

  2

  ) and heterocycles by various processes. Therefore, Nitriles are interesting reagents in the synthesis of robust and diverse molecular libraries that may be used in high throughput screening assays on the search for novel drug candidates [9 , 10 ].

  Scheme (2)) Example of the conversion of Nitriles into some common functional groups: ketone (A), carboxylic acid (B), aldehyde (C), and amine (D).

  Five membered-ring azaheterocycles have been extensively explored in medicinal chemistry and are present in many marketed drugs. Some of them, such as pyrrole, indole, triazole, and imidazole are found in top-selling drugs [11 , 12 ] and many more are found in bioactive molecules [13 , 14 ].

  Therefore, considering the importance of the nitrile functional group as a precursor to many azaheterocycles, in this work we will review the new synthetic methodologies, reported from 2014 to 2020, for the synthesis of some prominent 5-membered azaheterocycles via

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  Science of Synthesis: Houben-Weyl Methods of Molecular Transformations Vol. 19

  Three Carbon-Heteroatom Bonds: Nitriles, Isocyanides, and Derivatives

  • Shun-Ichi Murahashi(Author)
  • 2014(Publication Date)
  • Thieme Chemistry

    (Publisher)

  There are a significant number of Nitriles among the wealth of molecules found in interstellar clouds, functioning as raw materials for a surprisingly rich chemistry. [39] It is noted that 72 reagents containing a cyano group are listed in the Encyclopedia of Reagents for Organic Synthesis, [40] providing methods to intro- duce a cyano group or carry out reactions with the Nitriles. There are several other useful accounts of reactions of Nitriles. [41–45] Some more recent synthetic applications of com- pounds containing cyano groups are presented here. Nitriles are activated by low-valent ruthenium and iridium hydride complexes and undergo reactions with nucleophiles and electrophiles under neutral conditions. [46] Thus, hydration of Nitriles to give amides is carried out with only 1–2 molar equivalents of water in 1,2-dimethoxyethane at 120 8C under neutral conditions and gives excellent yields (Scheme 17). Similarly, Nitriles can be esterified and amidated; the catalysts also activate the C-H bonds of Nitriles for further addition reactions with electrophiles. [46] Scheme 17 Catalytic Hydration of Nitriles under Neutral Conditions [46] R 1 CN + H 2 O RuH 2 (PPh 3 ) 4 (cat.) O R 1 NH 2 A novel three-component reaction involving Nitriles, alkenes, and water in the presence of an iridium polyhydride complex as a Lewis acid and base ambiphilic catalyst affords glutarimides, which are versatile intermediates for the synthesis of biologically active compounds (Scheme 18). [47] Scheme 18 Formation of Glutarimides from Nitriles [47] IrH 5 (P-iPr 3 ) 2 (cat.) R 1 CN R 2 R 5 CN R 3 R 4 + + 2 H 2 O − NH 3 N H O O R 5 R 3 R 4 R 1 R 2 The conversion of tertiary amines into Æ-cyano tertiary amines can be accomplished by aerobic ruthenium-catalyzed oxidative cyanation with sodium cyanide (see Section 19.5.3.4.2). [48] 86 Science of Synthesis 19.5 Nitriles

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  Science of Synthesis: Catalytic Reduction in Organic Synthesis Vol. 2

  • Johannes G. de Vries(Author)
  • 2018(Publication Date)
  • Thieme

    (Publisher)

  2.9 Catalytic Reduction of Nitriles D. B. Bagal and B. M. Bhanage General Introduction Nitriles are versatile intermediates that can be easily converted into a variety of function-al groups such as amines, amides, acids, esters, aldehydes, thioamides, amidoximes, and ketones. In particular, the selective catalytic hydrogenation of Nitriles represents an atom-economic and efficient route to obtain amines, which are versatile intermediates and precursors in the synthesis of various natural products, pharmaceuticals, dyes, pig-ments, agrochemicals, and polymers. [1–8] Among amines, the terminal primary amines are the most useful, but their selective synthesis is a challenging task due to their high reactivity. However, the synthesis of amines by the reduction of Nitriles has been less in-vestigated so far compared to synthesis via the reduction of C = C bonds, carbonyl groups, C = N bonds, and nitro groups. This is primarily due to the high redox potential of Nitriles compared to other carboxylic acid derivatives, the low C — CN bond dissociation energy, which leads to undesired reductive decyanation side reactions via fragmentation to alkyl radicals and cyanide anions, and the instability of imine/iminium intermediates under the reaction conditions, which can result in alcoholysis, transamination, or reduc-tive polymerization pathways. [9–12] Nitriles are commonly reduced using either stoichiometric amounts of a metal hy-dride, [13–20] such as lithium aluminum hydride (room temperature) or sodium borohydride (at higher temperatures or in the presence of a heterogeneous catalyst based on nick-el, [21–23] palladium, [24–26] or cobalt, [27,28] etc.), or using molecular hydrogen or formate as a hydrogen source. [29–31] Although metal hydrides are effective reagents, stoichiometric amounts of waste metal salts are produced which require separation and disposal, and hence, such methods are not environmentally benign.

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  Toxicology of Cyanides and Cyanogens

  Experimental, Applied and Clinical Aspects

  • Alan H. Hall, Gary E. Isom, Gary A. Rockwood, Alan H. Hall, Gary E. Isom, Gary A. Rockwood(Authors)
  • 2015(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  Chapter 12 Cyanogenic aliphatic Nitriles Stephen W. Borron

  At a Glance

  • Aliphatic Nitriles exist as monoNitriles (with 1 cyanide moiety) or diNitriles (with 2 cyanide moieties).
  • Aliphatic Nitriles are widely used in industry for a variety of applications.
  • While the parent aliphatic nitrile compounds may have their own toxicity, metabolic release of cyanide after systemic absorption by the oral, inhalational, or dermal routes accounts for the majority of their toxicity.
  • The onset of cyanide poisoning signs and symptoms is often delayed, and toxic manifestations may recur due to continued metabolic release of cyanide.
  • Human poisonings have been reported with acetonitrile, adiponitrile, isobutyronitrile, glycolonitrile, lactonitrile, propionitrile, succinonitrile, and acetone cyanohydrin.
  • Specific cyanide antidotes have been efficacious in cases of human aliphatic nitrile poisoning; the most clinical experience has been with sodium thiosulfate, alone or in combination with other cyanide antidotes.

  12.1 Overview

  This chapter addresses some aliphatic Nitriles of industrial importance, essentially excluding acrylonitrile, which is covered in Chapter 13 . Cyanogenic glycosides, including those found in foodstuffs, such as cassava, and in drugs, such as laetrile, are not discussed here.

  Aliphatic Nitriles have the general formula R-CN and exist as monoNitriles and diNitriles (one and two functional groups, respectively). The closely related cyanohydrins have a general formula of (see Figure 12.1 ). The Nitriles are an extremely important chemical family, employed as solvents (acetonitrile, propionitrile), in the manufacture of plastics and synthetic rubber (acrylonitrile, adiponitrile), in drug manufacture (acetonitrile, glycolonitrile, propionitrile), in petroleum refining and hydrocarbon extraction (acetonitrile, propionitrile) and as intermediates in the manufacture of other chemicals (ketones, esters) and fibers. Some of the important physical properties of Nitriles involved in human poisonings are found in Table 12.1 . More than 40 Nitriles appear in the U.S. Environmental Protection Agency's High Production Volume Information System (HPVIS), indicating that quantities of 1,000,000 pounds or more of these chemicals are produced or imported each year into the United States (Table 12.2

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