Chemistry
Halogenation of Alcohols
Halogenation of alcohols is a chemical reaction in which a halogen atom, such as chlorine or bromine, is added to an alcohol molecule. This process typically involves the use of a halogenating reagent, such as phosphorus tribromide or thionyl chloride, to replace the hydroxyl group of the alcohol with a halogen atom. The resulting halogenated alcohol product can have various applications in organic synthesis.
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9 Key excerpts on "Halogenation of Alcohols"
eBook - ePub- Andrew F. Parsons(Author)
- 2013(Publication Date)
- Wiley(Publisher)
5 Br.- An alicyclic halogenoalkane has the carbon atoms in a closed ring, but the ring is not aromatic, e.g. bromocyclohexane, C6 H11 Br.
- An aromatic halogenoalkane has the carbon atoms in a closed ring and the ring is aromatic, e.g. bromobenzene, C6 H5 Br.
The formation of bromobenzene from benzene is discussed in Section 7.2.15.2 Preparation
5.2.1 Halogenation of Alkanes
Chloroalkanes (RCl) or bromoalkanes (RBr) can be obtained from alkanes (RH) by reaction with chlorine or bromine gas, respectively, in the presence of UV radiation. The reaction involves a radical chain mechanism.Radicals are introduced in Section 4.1 Radical reactions are discussed in Section 4.6.2This is a substitution reaction as a hydrogen atom on the carbon is substituted for a Cl or Br atom. A mixture of halogenated products is usually obtained if further substitution reactions can take place.Chloroalkanes, such as CH2 Cl2 (dichloromethane), are common solvents in organic synthesisPrimary, secondary and tertiary halogenoalkanes are defined in Section 2.1The ease of halogenation depends on whether the hydrogen atom is bonded to a primary, secondary or tertiary carbon atom. A tertiary hydrogen atom is more reactive because reaction with a halogen atom (X• ) produces an intermediate tertiary radical, which is more stable (and therefore more readily formed) than a secondary or primary radical (Section 4.3).5.2.2 Halogenation of Alcohols
Alcohols (ROH) are converted into halogenoalkanes using a number of methods. All methods involve ‘activating’ the OH group to make this into a better leaving group (Section 5.3.1.4). Reaction mechanisms are introduced in Section 4.11The mechanism of these reactions depends on whether a primary (RCH2 OH), secondary (R2 CHOH) or tertiary alcohol (R3
eBook - ePubOrganic Chemistry
Concepts and Applications
- Allan D. Headley(Author)
- 2019(Publication Date)
- Wiley(Publisher)
Alkanes are fairly inert compounds; some alkanes are used as solvents to provide inert media for different reactions that we will see in later chapters. In addition to combustion, alkanes undergo another type of reaction that is very important to organic chemists, and that is the reaction with halogens, specifically chlorine or bromine in the presence of energy in the form of heat or light. As the name suggests, this reaction involves the reaction of alkanes and bromine or chlorine and is called bromination or chlorination of alkanes, respectively. These reactions are performed in the presence of light or heat and are described as substitution reactions since a hydrogen or more than one hydrogen atoms of an alkane reactant are substituted for a halogen or more than one halogen in the product. Most of the reactions that will be encountered in this chapter involve the substitution of one hydrogen in the alkane for a halogen in the product.The products produced upon the chlorination of alkanes are alkyl halides, most are important industrial raw material for the synthesis of numerous other chemicals. For example, chloromethane was used once as a refrigerant, but discontinued owing to its flammability and toxicity. Today, it is widely used as a chemical intermediate for the production of different compounds, including polymers. Other chloroalkanes are widely used as a solvent in the research labs and in the production of rubber and in the petroleum refining industry. The chlorination of methane is shown in Reaction (14‐5) .(14‐5)To be able to predict the products of these and other similar reactions, a thorough understanding of how the reaction occurs is essential. Before we examine the reaction mechanism for the chlorination of alkanes, let us examine the process of bond reorganization for the reaction shown in Reaction (14‐5) . It should be obvious that this reaction is a substitution reaction in which a Cl─Cl bond has to be broken and the chlorine atoms form two new bonds, a new H─Cl bond and a new C─Cl bond in the CH3
eBook - ePubOrganic Chemistry Study Guide
Key Concepts, Problems, and Solutions
- Robert J. Ouellette, J. David Rawn(Authors)
- 2014(Publication Date)
- Elsevier(Publisher)
Also, electronegative substituents near the carbon atom bearing the hydroxyl group increase its acidity. Halogen substituents inductively withdraw electron density from the oxygen atom and weaken the O—H bond. The halogens also stabilize the negative charge of the conjugate base—an alkoxide ion.Alcohols, like water, can be protonated. The product is a conjugate acid known as an alkyloxonium ion.9.12 Substitution Reactions of Alcohols
The hydroxyl group of alcohols react with hydrogen halides such as HBr to give haloalkanes. The order of reactivity is tertiary > secondary > primary. Hydrogen bromide suffices to form bromoalkanes, but zinc chloride is required as a catalyst for the reaction with hydrogen chloride. The substitution reactions of alcohols parallel that of haloalkanes. However, hydroxide ion is not the leaving group. Protonation of the hydroxyl group must occur to allow water to become the leaving group. In general, a weaker base is a better leaving group than a stronger base. Since hydroxide ion is a stronger base than water, it is a poor leaving group in both SN 1 and SN 2 reactions.The order of reactivity of alcohols in SN 1 reactions is tertiary > secondary > primary. This order parallels the stability of the carbocation intermediates that form in the reaction. This order of reactivity is reversed for SN 2 reactions; however, tertiary alcohols do not react by an SN 2 mechanism.9.13 Alternate Methods for the Synthesis of Alkyl Halides
Since undesirable rearrangements occur in acid-catalyzed reactions of alcohols, other methods have been developed to synthesize alcohols that do not require acid. In this section, we discussed two additional reagents that convert alcohols to haloalkanes. They are used for secondary and primary alcohols which react slowly with hydrogen halides.Thionyl chloride is used to convert alcohols to chloroalkanes. The by-products are sulfur dioxide and hydrogen chloride, both of which escape from the solution as gases. Phosphorus tribromide is used to convert alcohols to bromoalkanes. The by-product, phosphorous acid, is soluble in water.
eBook - ePubOrganic Chemistry
An Acid-Base Approach, Third Edition
- Michael B. Smith(Author)
- 2022(Publication Date)
- CRC Press(Publisher)
Vogel’s Textbook of Practical Organic Chemistry, 5th ed., Longman, Essex, UK, 1994, Exp. 5.49, p. 556.Figure 11.8The reaction of primary alcohols and tertiary alcohols with HCl or HBr.- 11.16 Write the final product via SN 1 when 2,2-dimethylpentan-3-ol is treated with conc HCl.
11.5.2 Sulfur and Phosphorous Halide Reagents
There are times when the use of mineral acids in chemical reactions must be avoided because of deleterious effects to other functional groups in the molecule. Other inorganic reagents are available that convert alcohols to alkyl chlorides, bromides or iodides. The most common inorganic chlorinating reagents are sulfur and phosphorous halides. The sulfur reagent thionyl chloride is used quite often but phosphorus trichloride, phosphorus pentachloride, and phosphorus oxychloride are also common. The structures of these compounds are shown. The common names are provided along with the IUPAC names. Shorthand notation for these reagents is shown with each structure (SOCl2 , PCl3 , PCl5 , and POCl3 ). Fluoride reagents will not be discussed.Primary, secondary, or tertiary alcohols react with these reagents to give an alkyl chloride, ROH ⟶ RCl, or an alkyl bromide, ROH ⟶ RBr. The sulfur or the phosphorus atom in these reagents react as Lewis acids with the electron-donating oxygen atom of an alcohol. A typical experiment heats heptan-1-ol with thionyl chloride for 4 hours at reflux to give 1-chloroheptane in 77% yield.10 Thionyl chloride reacts with the oxygen atom of heptan-1-ol to give oxonium ion 16, as shown in Figure 11.9 . A second reaction regenerates the S=O bond as HCl is lost, forming a chlorosulfite product (heptane chlorosulfite; the IUPAC name is heptyl sulfochloridite), 17. Alternative mechanisms are possible for loss of HCl, including an intermolecular process to lose HCl, but this one will be used for simplicity. The intramolecular reaction of the chlorine atom at carbon generates 1-chloroheptane with loss of sulfur dioxide, O=S=O. The gaseous HCl and SO2
eBook - ePubFluorine in Life Sciences: Pharmaceuticals, Medicinal Diagnostics, and Agrochemicals
Progress in Fluorine Science Series
- Gunter Haufe, Frederic Leroux(Authors)
- 2018(Publication Date)
- Academic Press(Publisher)
8 Influence of fluorination on alcohol hydrogen-bond donating properties Bruno Linclau 1, Jéôme Graton 2, and Jean-Yves Le Questel 2 1 Chemistry, University of Southampton, Southampton, United Kingdom 2 CEISAM UMR CNRS 6230, University of Nantes, Nantes, France Abstract Hydrogen bonding represents the most specific molecular interaction in biological recognition processes, and the controlled modulation of hydrogen-bond properties of functional groups present in ligands is of great interest. The introduction of fluorine atoms in the vicinity of functional groups is one of the ways this can be achieved. In this chapter, a number of hydrogen-bond acidity scales are reviewed, with a focus on the hydrogen-bond donating capacity of alcohols. An overview of experimental data showing how the hydrogen-bond donating capacity of alcohols is modulated by fluorination is given, followed by a rationalization of these results. Computational methodology to describe and predict hydrogen bonds is discussed, with a focus on a convenient method for accurate alcohol hydrogen-bond donating capacity prediction. Keywords Alcohol; Conformational analysis; Electrostatic potential; Fluorohydrin; Hydrogen-bond acidity Chapter Outline 1. Introduction 2. Hydrogen-bond donating capacity scales 3. Theoretical descriptors for hydrogen bonding 4. Hydrogen-bond donating capacity of alcohols 5. Hydrogen-bond donating capacity of fluorohydrins 6. Rationalization of the influence of fluorination 7. The Kenny parameter for hydrogen-bond acidity prediction 8. Conclusion References 1. Introduction Hydrogen bonds (HBs) are recognized as the most important specific molecular interactions in biological recognition processes [1]. Despite their well-defined structural features (distances, valence angles), the properties of HBs are known to be strongly influenced by the environment (intra- and/or intermolecular) [ 2, 3 ]
eBook - ePubSurvival Guide to Organic Chemistry
Bridging the Gap from General Chemistry
- Patrick E. McMahon, Bohdan B. Khomtchouk, Claes Wahlestedt(Authors)
- 2016(Publication Date)
- CRC Press(Publisher)
strong acid.Identify the mechanism based on the identity of X and the substitution pattern on the electrophilic carbon (primary, secondary, or tertiary).- For primary alcohols; primary and secondary alkyl halides/sulfonates: SN2 .
- For secondary and tertiary alcohols; tertiary alkyl halides/sulfonates: SN1 .
- Identify the correct constitutional isomer: directly exchange the nucleophile and leaving group, bonding the correct nucleophilic atom to the electrophilic carbon. Complete any proton transfers required to achieve normal, neutral bonding in the final products: Add or remove protons as necessary .
Identify the correct stereochemistry:- Determine if stereoisomers are possible from the structure of the organic molecule.
- If no stereoisomers are possible, the problem is complete; show only the correct constitutional isomer from step (5).
- If stereoisomers are possible, use the mechanism determined from step (4):
- SN1 is not stereospecific ; it produces approximately 50% (±10%) of each of the two possible stereoisomers of a stereoisomer pair: show only the correct constitutional isomer.
- SN2 is stereospecific ; it produces 100% inversion of stereoconfiguration: show the correct resulting stereoisomer.
12.4 ELIMINATION REACTIONS OF ALCOHOLS AND ALKYL HALIDES
12.4.1 GENERAL REACTION CONCEPTS
- An elimination reaction proceeds through removal of two atoms or atom groupings from neighboring carbons to form a double bond.
- Each of the neighboring carbons breaks one sigma bond, to be replaced by a mutual pi- bond between them.
- In most cases, one of the removed atoms is hydrogen ; the other is an atom or atom grouping that can be usually identified as a typical leaving group
eBook - ePubUnderstanding Advanced Organic and Analytical Chemistry
The Learner's ApproachRevised Edition
- Kim Seng Chan, Jeanne Tan;;;(Authors)
- 2016(Publication Date)
- WS EDUCATION(Publisher)
CHAPTER 7
Halogen Derivatives
7.1 Introduction
Halogenoalkanes, also known as alkyl halides, are saturated organic compounds that contain the −C−X functional group (X = F, Cl, Br or I). They are important derivatives of alkanes and have the general formula Cn H2n+1 X. An example is bromoethane:Halogenoalkanes do not occur naturally. In fact, they are the by-products of the reaction of alkanes or alkenes with halogen, as these hydrocarbons are commonly found in petroleum. Halogenoalkanes are generally known as the “workhorse” in organic chemistry as they are very useful intermediates to be converted to other more important specialty chemicals of greater economic value. Some halogenoalkanes, such as chlorofluorocarbon, can also be harmful to the environment.Halogenoarenes (or aryl halides) are aromatic compounds with a halogen atom directly attached to the benzene ring. Similar to halogenoalkanes, halogenoarenes do not occur naturally and are in fact synthesized by reacting aromatic compounds isolated from petroleum with halogens.7.2 Nomenclature
A halogenolkane is obtained when one or more hydrogen atoms of an alkane molecule have been replaced by halogen atoms via the free radical substitution reaction. Other than this, halogenoalkanes can also be obtained when hydrogen halide (HX) or the diatomic halogen molecules add across an alkene double bond through the electrophilic addition mechanism. Thus, one can simply perceive halogenoalkanes as substituted alkanes. Therefore, halogenoalkanes are named in a similar manner to alkanes — the suffix ends in — ane
eBook - PDF- T. W. Graham Solomons, Craig B. Fryhle, Scott A. Snyder(Authors)
- 2016(Publication Date)
- Wiley(Publisher)
The result is formation of a halohydrin as the major product. If the halogen is bromine, it is called a bromohydrin, and if chlorine, a chlorohydrin. + C C X OH X 2 + + H 2 O + HX Halohydrin (major) C C X X vic-Dihalide (minor) X = Cl or Br C C Halohydrin formation can be described by the following mechanism. Halohydrin Formation from an Alkene A MECHANISM FOR THE REACTION [ [ Step 1 C C X X C C X + Halonium ion + X - Halide ion This step is the same as for halogen addition to an alkene (see Section 8.11A). C C X + Halonium ion + O C C Protonated halohydrin Here, however, a water molecule acts as the nucleophile and attacks a carbon of the ring, causing the formation of a protonated halohydrin. H H O H H + O H H C C X X O H Halohydrin + H O + H H The protonated halohydrin loses a proton (it is transferred to a molecule of water). This step produces the halohydrin and hydronium ion. Steps 2 and 3 δ+ δ- The first step is the same as that for halogen addition. In the second step, however, the two mechanisms differ. In halohydrin formation, water acts as the nucleophile and attacks one carbon atom of the halonium ion. The three-membered ring opens, and a protonated halohydrin is produced. Loss of a proton then leads to the formation of the halohydrin itself. Write a mechanism to explain the following reaction. + (as a racemic mixture) Br OH Br OH Br 2 H 2 O PRACTICE PROBLEM 8.15 366 CHAPTER 8 ALKENES AND ALKYNES II: Addition Reactions • If the alkene is unsymmetrical, the halogen ends up on the carbon atom with the greater number of hydrogen atoms. Bonding in the intermediate bromonium ion is unsymmetrical. The more highly substi- tuted carbon atom bears the greater positive charge because it resembles the more stable carbocation. Consequently, water attacks this carbon atom preferentially.
- Mathias Christmann, Jean-Francois Paquin, Steven M. Weinreb, Mathias Christmann, Jean-Francois Paquin, Steven M. Weinreb(Authors)
- 2017(Publication Date)
- Thieme Chemistry(Publisher)
397 34.9.3 b-Fluoro Alcohols (Update 2017) K. Shibatomi General Introduction The synthesis of b-fluoro alcohols was reviewed in Section 34.9.1, and the first update (Section 34.9.2) was published in 2013, with an emphasis on the asymmetric synthesis of this class of compounds. This update further focuses on asymmetric synthesis, especially enantioselective approaches, and includes methods based on the a-fluorination of car- bonyl compounds and subsequent reduction. While the latter is not a straightforward process, it is a powerful method for the preparation of a variety of b-fluoro alcohols with high enantiopurity, owing to the recent significant advances in the asymmetric a-fluori- nation of carbonyl compounds. 34.9.3.1 Method 1: Fluorination of Allylic Alcohols The allylic fluorination of unactivated alkenes by p-activation of the C=C bond with an electrophilic fluorinating agent has rarely been achieved. An elegant enantioselective fluorination of allylic alcohols was recently reported (Scheme 1). [1] The treatment of allyl- ic alcohols 3 with 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetra- fluoroborate) (Selectfluor, 2), 4-tolylboronic acid, and disodium hydrogen phosphate af- fords the corresponding b-fluoro homoallylic alcohols 4 in good yields and high enantio- selectivities in the presence of chiral phosphoric acid 1 as catalyst. The reaction is pro- posed to proceed via the formation of a boronic monoester intermediate, with the boron- ic ester moiety acting as directing group for the fluorination by interacting with the chiral phosphate anion. Interestingly, with allylic alcohol 6 as substrate, this catalyst system can produce either enantiomer of 7 in high enantiopurity in the presence of the same chi- ral catalyst 5, just by changing the structure of the achiral boronic acid (Scheme 2).
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