Chapter 15
Alcohols Preparation and Physical Properties
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Structure
- Alcohols are compounds of the general formula ROH, where R is any alkyl or substituted alkyl group. The group may be primary, secondary, or tertiary; it may be open-chain or cyclic; it may contain a double bond, a halogen atom, or an aromatic ring. For example:
- All alcohols- contain the hydroxyl (- OH) group, which, as the functional group, determines the properties characteristic of this family. Variations in structure of the R group may affect the rate at which the alcohol undergoes certain reactions, and even, in a few cases, may affect the kind of reaction.
- Compounds in which the hydroxyl group is attached directly to an aromatic ring are not alcohols; they are phenols and differ so markedly from the alcohols that we shall consider them in a separate chapter.
Classification
- We classify a carbon atom as primary, secondary, or tertiary according to the number of other carbon atoms attached to it. An alcohol is classified according to the kind of carbon that bears the OH group:
- One reaction, oxidation, which directly involves the hydrogen atoms attached to the carbon bearing the OH group, takes an entirely different course for each class of alcohol. Usually, however, alcohols of different classes differ only in rate or mechanism of reaction, and in a way consistent with their structures. Certain substituents may affect reactivity in such a way as to make an alcohol of one class resemble the members of a different class; benzyl alcohol, for example, though formally a primary alcohol, often acts like a tertiary alcohol. We shall find that these variations, too, are consistent with the structures involved.
Nomenclature
- Alcohols arc named by three different systems. For the simpler alcohols the common names, which we have already encountered (Sec. 5.19), are most often used. These consist simply of the name of the alkyl group followed by the word alcohol. For example:
- Finally, there is the most versatile system, the IUPAC. The rules are:
- Select as the parent structure the longest continuous carbon chain that contains the OH group \ then consider the compound to have been derived from this structure by replacement of hydrogen by various groups. The parent structure is known as ethanol, propanol, butanol, etc., depending upon the number of carbon atoms; each name is derived by replacing the terminal -e of the corresponding alkane name by -old.
- Indicate by numbers the positions of other groups attached to the parent chain.
Physical properties
- The compounds we have studied so far, the various hydrocarbons, are nonpolar or nearly so and have the physical properties that we might expect of such compounds: the relatively low melting points and boiling points that are characteristic of molecules with weak intermolecular forces; solubility in non-polar solvents and insolubility in polar solvents like water.
- Alcohols, in contrast, contain the very polar OH group. In particular, this group contains hydrogen attached to the very electronegative element, oxygen, and therefore permits hydrogen bonding the physical properties show the effects of this hydrogen bonding.
- Let us look first at boiling points. Among hydrocarbons the factors that determine boiling point seem to be chiefly molecular weight and shape; this is to be expected of molecules that are held together chiefly by van der Waals forces. Alcohols, too, show increase in boiling point with increasing carbon number, and decrease in boiling point with branching. But the unusual thing about alcohols is that they boil so high.
- The answer is, of course, that alcohols, like water, are associated liquids: their abnormally high boiling points are due to the greater energy needed to break the hydrogen bonds that hold the molecules together. Although ethers and aldehydes contain oxygen, they contain hydrogen that is bonded only to carbon; these hydrogens are not positive enough to bond appreciably with oxygen.
- Infrared spectroscopy (Sec. 13.4) has played a key role in the study of hydrogen bonding. In dilute solution in a non-polar solvent like carbon tetrachloride (or in the gas phase), where association between molecules is minimal, ethanol, for example, shows an O H stretching band at 3640 cm" . 1As the concentration of ethanol is increased; this band is gradually replaced by a broader band at 3350 cm" The bonding of hydrogen to the second oxygen weakens the O H bond and lowers the energy and hence the frequency of vibration.
- The solubility behavior of alcohols also reflects their ability to form hydrogen bonds. In sharp contrast to hydrocarbons, the lower alcohols are miscible with water. Since alcohol molecules are held together by the same sort of intermodular forces as water molecules, there can be mixing of the two kinds of molecules: the energy required to break a hydrogen bond between two water molecules, or two alcohol molecules is provided by formation of a hydrogen bond between a water molecule and an alcohol molecule.
Industrial source
- If an organic chemist were allowed to choose ten aliphatic compounds with which to be stranded on a desert island, he would almost certainly pick alcohols. From them he could make nearly every other kind of aliphatic compound: alkenes, alkyl halides, ethers, aldehydes, ketones, acids, esters, and a host of others. From the alkyl halides, he could make Grignard reagents, and from the reaction between these and the aldehydes and ketones obtain more complicated alcohols and so on. Our stranded chemist would use his alcohols not only as raw materials but frequently as the solvents in which reactions are carried out and from which products are recrystallized.
- For alcohols to be such important starting materials in aliphatic chemistry, they must be not only versatile in their reactions but also available in large amounts and at low prices. There are two principal ways to get the simple alcohols that are the backbone of aliphatic organic synthesis: by hydration of alkenes obtained from the cracking of petroleum, and by fermentation of carbohydrates. In addition to these two chief methods, there are some others that have more limited application.
- Hydration of alkenes. We have already seen that alkenes containing up to four or five carbon atoms can be separated from the mixture obtained from the cracking of petroleum. We have also seen that alkenes are readily converted into alcohols either by direct addition of water, or by addition of sulfuric acid followed by hydrolysis. By this process there can be obtained only those alcohols whose formation is consistent with the application of Markovnikov's rule: for example, isopropyl but not w-propyl, sec-butyl but not w-butyl, terf-butyl but not isobutyl. Thus the only primary alcohol obtainable in this way is ethyl alcohol.
- Fermentation of sugars by yeast, the oldest synthetic chemical process used by man, is still of enormous importance for the preparation of ethyl alcohol and certain other alcohols. The sugars come from a variety of sources, mostly molasses from sugar cane, or starch obtained from various grains; the name "grain alcohol" has been given to ethyl alcohol for this reason.
- When starch is the starting material, there is obtained, in addition to ethyl alcohol, a smaller amount offusel oil (German: Fusel, inferior liquor), a mixture of primary alcohols: mostly isopentyl alcohol with smaller amounts of w-propyl alcohol, isobutyl alcohol, and 2-methyl-l-butanol, known as active amyl alcohol (amyl pentyl).
- (CH3)2CHCH2CH(NH3 * )COO - CH3CH2CH(CH3KH(NH,*)COO
Ethyl alcohol
- In industry ethyl alcohol is widely used as a solvent for lacquers, varnishes, perfumes, and flavorings; as a medium for chemical reactions; and in recrystallizations. In addition, it is an important raw material for synthesis; after we have learned more about the reactions of alcohols (Chap. 16), we can better appreciate the role played by the leading member of the family. For these industrial purposes ethyl alcohol is prepared both by hydration of ethylene and by fermentation of sugar from molasses (or sometimes starch); thus, its ultimate source is petroleum, sugar cane, and various grains.
- Ethyl alcohol is the alcohol of "alcoholic" beverages. For this purpose, it is prepared by fermentation of sugar from a truly amazing variety of vegetable sources. The particular beverage obtained depends upon what is fermented (rye or corn, grapes or elderberries, cactus pulp or dandelions), how it is fermented (whether carbon dioxide is allowed to escape or is bottled up, for example), and what is done after fermentation (whether or not it is distilled). The special flavor of a beverage is not due to the ethyl alcohol but to other substances either characteristic of the particular source, or deliberately added.
- Medically, ethyl alcohol is classified as a hypnotic (sleep producer); it is less toxic than other alcohols. (Methanol, for example, is quite poisonous: drinking it, breathing it for prolonged periods, or allowing.
- Except for alcoholic beverages, nearly all the ethyl alcohol used is a mixture of 95% alcohol and 5% water, known simply as 95% alcohol. What is so special about the concentration of 95%? Whatever the method of preparation, ethyl alcohol is obtained first mixed with water; this mixture is then concentrated by fractional distillation. But it happens that the component of lowest boiling point is not ethyl alcohol (bop 78.3) but a binary azeotrope containing 95% alcohol and 5% water (b.p. 78.15). As an azeotrope, it of course gives a vapor of the same composition, and hence cannot be further concentrated by distillation no matter how efficient the fractionating column used.
Preparation of alcohols
- Most of the simple alcohols and a few of the complicated ones are available from the industrial sources described in. Other alcohols must be prepared by one of the methods outlined blew.
- We can follow either of two approaches to the synthesis of alcohols or, for that matter, of most other kinds of compounds, (a) We can retain the original carbon skeleton, and simply convert one functional group into another until we arrive at an alcohol; or (b) we can generate a new, bigger carbon skeleton and at the same time produce an alcohol.
- By far the most important method of preparing alcohols is the Grignard synthesis. This is an example of the second approach, since it leads to the formation of carbon-carbon bonds. In the laboratory a chemist is chiefly concerned with preparing the more complicated alcohols that he cannot buy; these are prepared by the Grignard synthesis from rather simple starting materials. The alkyl halides from which the Grignard reagents are made, as well as the aldehydes and ketones themselves, are most conveniently prepared from alcohols; thus, the method ultimately involves the synthesis of alcohols from less complicated alcohols.
- Alcohols can be conveniently made from compounds containing carbon double bonds in two ways; by oxymercuration-Demer curation and by hydroboration-oxidation. Both amount to addition of water to the double bond, but with opposite orientation- Markovnikov and anti-Markovnikov and hence the two methods neatly complement each' other.
- Hydrolysis of alkyl halides is severely limited as a method of synthesizing alcohols, since alcohols are usually more available than the corresponding halides; indeed, the best general preparation of halides is from alcohols. The synthesis of benzyl alcohol from toluene, however, is an example of a useful application of this method.
Oxymercuration-Demer curation
- Alkenes react with mercuric acetate in the presence of water to give hydroxymercurial compounds which on reduction yield alcohols.
- The first stage, oxymercuration, involves addition to the carbon-carbon double bond of OH and HgOAc. Then, in demarcation, the HgOAc is replaced by H. The reaction sequence amounts to hydration of the alkene but is much more widely applicable than direct hydration.
- The two-stage process of oxymercuration-demercuration is fast and convenient, takes place under mild conditions, and gives excellent yields often over 90%. The alkene is added at room temperature to an aqueous solution of mercuric acetate diluted with the solvent tetrahydrofuran. Reaction is generally complete within minutes. The organomercurial compound is not isolated but is simply reduced in situ by sodium borohydride, NaBH4 . (The mercury is recovered as a ball of elemental mercury.)
- Oxymercuration-desecrators is highly regiospecific and gives alcohols corresponding to Markovnikov addition of water to the carbon-carbon double bond. For example:
- Oxymercuration involves electrophilic addition to the carbon-carbon double bond, with the mercuric ion acting as electrophile. The absence of rearrangement and the high degree of stereospecificity (typically anti) in the oxymercuration step argues against an open carbonium ion as intermediate. Instead, it has been proposed, there is formed a cyclic mercurified ion, analogous to the bromonium.
- Although the Demer curation reaction is not really understood, free radicals have been proposed as intermediates. Whatever the mechanism, Demer curation is generally not stereospecific and can, in certain special cases, be accompanied by rearrangement.
Hydroboration-oxidation
- The reaction procedure is simple and convenient, the yields are exceedingly high, and, as we shall see, the products are ones difficult to obtain from alkenes in any other way.
- Diborane is the dimer of the hypothetical BH3 (horane) and, in the reactions that concern us, acts much as though it were BH3 . Indeed, in tetrahydrofuran, one of the solvents used for hydroboration, the reagent exists as the monomer, in the form of an acid-base complex with the solvent.
- Hydroboration involves addition to the double bond of BH3 (or, in following stages, BH2 R and BHR2), with hydrogen becoming attached to one doubly bonded carbon, and boron to the other. The alkylborane can then undergo oxidation.
Orientation and stereochemistry of hydroboration
- Hydroboration-oxidation, then, converts alkenes into alcohols. Addition is highly regiospecific; the preferred product here, however, is exactly opposite to the one formed by oxyrnercuration-demercuration or by direct acid-catalyzed hydration. For example:
- The hydroboration-oxidation process gives products corresponding to anti-Markovnikov addition of water to the carbon-carbon double bond.
- The reaction of 3,3-dimethyl-l -butene illustrates a particular advantage of the method. Rearrangement does not occur in hydroboration evidently because carbonium ions are not intermediates and hence the method can be used without the complications that often accompany other addition reactions.
Mechanism of hydroboration
- Much of the usefulness of hydroboration-oxidation lies in the "unusual" orientation of the hydration. The OH simply takes the position occupied by boron in the intermediate alkylborane, and hence the final product reflects the orientation of the hydroboration step.
- The orientation appears to be unusual because hydrogen adds to the opposite end of the double bond from where it adds in ordinary electrophilic addition. But the fundamental idea in electrophilic addition is that the electrophilic part of the reagent the acidic part- -becomes attached, using the TT electrons, in such a way that the carbon being deprived of the TT electrons is the one best able to stand the deprivation. Thus, with propyJene as an example:
- Now, what is the center of acidity in BH3 ? Clearly, boron, with only six electrons. It is not at all surprising that boron should seek out the TT electrons of the double bond and begin to attach itself to carbon. In doing this, it attaches itself in such a way that the positive charge can develop on the carbon best able to accommodate.
CH3 -*CH CH2 : 8- H-B H H
- Unlike ordinary electrophilic addition, however, the reaction does not proceed to give a carbon mm ion. As the transition state is approached, the carbon that is losing the TT electrons becomes itself increasingly acidic: electron-deficient boron is acidic but so, too, is electron-deficient carbon. Not too far away is a hydrogen atom held to boron by a pair of electrons. Carbon begins to take that hydrogen, with its electron pair; boron, as it gains the TT electrons, is increasingly willing to release that hydrogen. Boron and hydrogen both add to the doubly bonded carbons in the same transition state:
- In view of the basic nature of alkcncs and the acidic nature of BH3 , the principal driving force of the reaction is almost certainly attachment of boron to carbon. In the transition state attachment of boron to C-l has proceeded to a greater extent than attachment of hydrogen to C--2. Thus, loss of (n) electrons by C-2 to the Q B bond exceeds its gain of electrons from hydrogen, and so C-2, the carbon that can best accommodate the charge, has become positive
Limitations of the Grignard synthesis
- The very reactivity that makes a Grignard reagent so useful strictly limits how we may use it. We must keep this reactivity in mind when we plan the experimental conditions of the synthesis, when we select the halide that is to become the Grignard reagent, and when we select the compound with which it is to react.
- In our first encounter with the Grignard reagent (Sec. 3.16), we allowed it to react with water to form an alkane; the stronger acid, water, displaced the extremely weak acid, the alkane, from its salt. In the same way, any compound containing hydrogen attached to an electronegative element oxygen, nitrogen, sulfur, or even triply-bonded carbon is acidic enough to decompose a Grignard reagent. A Grignard reagent reacts rapidly with oxygen and carbon dioxide, and with nearly every organic compound containing a carbon-oxygen or carbon-nitrogen multiple bond.
- We cannot prepare a Grignard reagent from a compound (e.g., HOCH2CH2Br) that contains, in addition to halogen, some group (e.g., OH) that will react with a Grignard reagent; if this were tried, as fast as a molecule of Grignard reagent formed it would react with the active group (OH) in another molecule to yield an undesired product (HOCH2CH2 H).
- We must be particularly watchful in the preparation of an aryi magnesium halide, in view of the wide variety of substituents that might be present on the benzene ring. Carboxyl (COOH), hydroxyl (--OH), amino (NH2), and SO3 Hall contain hydrogen attached to oxygen or nitrogen, and therefore are so acidic that they will decompose a Grignard reagent. We have just learned that a Grignard reagent adds to the carbonyl group (C -O), and we shall learn that it adds similarly to COOR and C~ N groups. The nitro (NO2) group oxidizes a Grignard reagent. It turns out that only a comparatively few groups may be present in the halide molecule from which we prepare a Grignard reagent; among these are R, Ar, -OR, and Cl (of an aryl chloride).
- By the same token, the aldehyde (or other compound) with which a Grignard reagent is to react may not contain other groups that are reactive toward a Grignard reagent. For example, a Grignard reagent would be decomposed before it could add to the carbonyl group of:
- These may seem like severe limitations, and they are. Nevertheless, the number of acceptable combinations is so great that the Grignard reagent is one of our most valuable synthetic tools. The kind of precautions described here must be taken in any kind of organic synthesis: we must not restrict our attention to the group we happen to be interested in but must look for possible interference by other functional groups.
Steroids
Cholesterol, notorious as the substance deposited on the walls of arteries and as the chief constituent of gallstones, is the kind of alcohol called a sterol. Sterols belong, in turn, to the class of compounds called steroids: compounds of the general formula.
- The rings are (generally) aliphatic. Lines like the vertical ones attached to the 10- and 13-positions represent angular methyl groups. Commonly, in cholesterol, for example.
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