BASIC
`PRINCIPLES OF
`ORGANIC
`CHEMISTRY
`
`SECOND EDITION
`
`John D.Roberts
`II
`Institute Professor of Chemistry
`California Institute of Technology
`
`Marjorie C.Caserio
`Professor of Chemistry
`University of California,
`
`Irvine
`
`W. A. Benjamin,
`
`Inc.
`
`Menlo Park. California
`London
`Amsterdam
`
`Reading. Massachusetts
`Don Mills. Ontario
`Sydney
`
`

`

`\,
`
`------L'<.
`\
`
`,
`
`\
`
`BASIC PRINCIPLES OF ORGANIC CHEMISTRY
`SECOND EDITION
`
`Inc.
`Copyright © 1977 and 1964 by W. A. Benjamin,
`Inc.
`Philippines copyright 1977 and 1964 by W. A. Benjamin,
`stored in a
`All rights reserved. No part of this publication may be reproduced,
`retrieval system, or
`transmitted,
`in any form or by any means, electronic,
`mechanical, photocopying,
`recording, or otherwise, without
`the prior written
`permission of the publisher. Printed in the United States of America. Published
`simultaneously
`in Canada. Library of Congress Catalog Card No. 77-076749.
`
`ISBN 0-8053-8329-8
`
`ABCDEFGHIJK-DO-7987
`
`Inc.
`W. A. Benjamin,
`2725 Sand Hill Road
`Menlo Park, California 94025
`
`

`

`20-6 Disaccharides; General Types and Properties
`
`927
`
`(Section 15-6C). Polynucleotides are polymers of nucleosides linked
`FADH2
`through phosphate ester bonds. Polynucleotides
`also are called nucleic acids
`(RNA and DNA) and are the genetic material of cells, as will be discussed in
`Chapter 25.
`
`hydrolysis of N-glyco-
`20-8 Work out a mechanism for the acid-induced
`Exercise
`sides. Pay special attention as to where a proton can be added to be most effective in
`assisting
`the reaction. Would you expect
`that adenosine would hydrolyze more, or
`less, readily than N-methyl-a-ribosylamine?
`Give your reasoning.
`
`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`20-6 DISACCHARIDES
`
`20-6A General Types and Properties
`Combinations of two or more of the simple sugars through glycoside linkages
`give substances known as polysaccharides. They also are called oligosaccha-
`rides if made from two to ten sugar units. The simplest oligosaccharides
`are
`disaccharides made of two molecules of simple sugars that can be the same or
`different. There are two ways in which the simple sugars can be joined with
`O-glycoside links, and it probably is easiest
`to visualize these as shown in the
`formulas, 22 and 23:
`"stripped-down"
`
`carbon
`
`~O~
`~~
`
`rr: acetal
`carbon
`
`8H~acetal
`G-- 0QH .-----hemiacetal
`
`~
`
`A
`
`hydroxy
`carbon
`
`H
`22
`
`carbon
`
`.
`
`->
`OH
`
`-'~ - ..... - ~
`
`G'
`
`~
`acetal
`carbon
`
`H
`
`23
`
`You should look at 22 and 23 carefully to be sure that you recognize the
`difference between them." In 22, sugar A is acting as a simple hydroxy com-
`pound,
`the aglycone of the sugar G to which it is linked by an O-glycoside
`
`"For now, we will ignore the possibility of different anomers of the disaccharide or
`their component
`sugars.
`
`

`

`928
`
`rv
`"
`~
`)
`
`G
`
`sugar
`
`I ~
`J?rO~
`
`~/
`
`'V0H
`
`a~IYCOne
`
`H
`
`22
`
`20 Carbohydrates
`linkage." Hydrolysis of 22 at the glycoside link then will proceed as follows:
`V
`H
`
`H H08H
`
`A
`
`+
`
`OH
`
`H
`
`OH
`
`) 8
`
`G
`
`H ° H<±>
`
`2,
`
`Disaccharides such as 22 are like glucose in being reducing sugars (Section
`20-2B), because Component A has the hemiacetal grouping that is opened
`easily to the aldehyde form in the mildly alkaline conditions used for the
`Tollen's and Fehling's solution oxidations. Because there is a free hemiacetal
`group, reducing sugars also form osazones and they mutarotate (Sections
`20-4B and 20-2C).
`Disaccharides of type 23 are different in that each sugar, G and G', is
`acting as both a glycoside sugar and as an aglycone. The linkage between
`I
`I
`them is that of a double-barreled acetal,-O-C-O-C-O-,
`I
`I
`no hemiacetal grouping in the molecule. Therefore these are nonreducing
`sugars as far as the standard tests go. However, hydrolysis of the O-glycoside
`linkages of 23 does generate reducing sugars with hemiacetal carbons:
`
`and there is
`
`H~O~
`~H
`
`to form oJigosaccharides was eluci-
`in which sugars are linked together
`6The manner
`dated by W. N. Haworth, who received the Nobel Prize in chemistry in 1937 for this
`and other contributions
`to research on the structures and reactions of carbohydrates.
`
`

`

`20-6 Disaccharides; General Types and Properties
`
`929
`
`the nonreducing disaccharides give none of the car-
`In general, we find that
`bonyl
`reactions observed for glucose,
`such as mutarotation and osazone
`formation, except when the conditions are sufficiently acidic to hydrolyze the
`acetal
`linkage.
`Among the more important disaccharides are sucrose, 24, maltose, 25,
`cellobiose, 26, and lactose, 27:
`
`o
`
`sucrose,24
`
`maltose,25
`
`OH -, lJ
`< \.J
`
`cellobiose,26
`
`OH
`
`lactose, 27
`
`lactose in the milk of
`Sucrose and lactose occur widely as the free sugars,
`mammals, and sucrose in fruit and plants (especially in sugar cane and sugar
`beet). Maltose is the product of enzymatic hydrolysis of starch, and cellobiose
`is a product of hydrolysis of cellulose.
`
`

`

`930
`
`20 Carbohydrates
`
`To fully establish the structure of a disaccharide, we must determine (1)
`the identity of the component monosaccharides;
`(2) the type of ring junction,
`furanose or pyranose,
`in each monosaccharide,
`as it exists in the disaccharide;
`(3) the positions that
`link one monosaccharide with the other; and (4) the
`anomeric configuration (a or f3) of this linkage.
`Hydrolysis of disaccharides with enzymes is very helpful in establish-
`ing anomeric configurations, because enzymes are highly specific catalysts for
`hydrolysis of the different
`types of glycoside linkages. For
`instance, a-D-
`glucosidase (maltase) catalyzes hydrolysis of o-o-glycosides more rapidly
`than of {3-D-glycosides.The enzyme emulsin (found in bitter almonds) in con-
`trast shows a strong preference for {3-D-glycosides over o-n-glycosides. Yeast
`invertase catalyzes hydrolysis of {3-D-fructosides.
`
`20-9 a. Which of the disaccharides,
`Exercise
`be reducing sugars?
`b. Determine the configuration
`either exor {3,
`the anomeric forms) will be produced
`(neglect
`c. Determine which monosaccharides
`on hydrolysis of 24 through 27. Be sure you specify the configurations
`as 0 or L.
`
`24 through 27, would you expect
`
`to
`
`of each of the anomeric carbons in 24 through 27 as
`
`20-68 Structure of Sucrose
`glucose and
`We know that
`sucrose consists of the two monosaccharides,
`fructose, because hydrolysis with acids or enzymes gives equal amounts of
`each hexose. Further,
`sucrose is not a reducing sugar, it forms no phenylosa-
`zone derivative, and it does not mutarotate. Therefore the anomeric carbons
`of both glucose and fructose must be linked through an oxygen bridge in
`sucrose. Thus sucrose is a glycosyl fructoside or, equally, a fructosyl glucoside.
`Because sucrose
`is hydrolyzed
`by enzymes
`that
`specifically assist
`hydrolysis of both a glycosides (such as yeast a-glucosidase) and {3-fructosides
`(such as invertase),
`it is inferred that
`the glucose residue is present as an
`a glucoside and the fructose residue as a {3fructoside.
`If so, the remaining
`uncertainty in the structure of sucrose is the size of the rings in the glucose and
`fructose residues.
`The size of the sugar rings in sucrose has been determined by the reac-
`tions shown in Figure 20-5. Methylation of sucrose with dimethyl sulfate in
`basic solution followed by hydrolysis of the octamethyl derivative gives
`2,3,4,6-tetra-O-methyl-D-glucopyranose
`(Section 20-4) and a tetra-O-methyl-
`D-fructose. This establishes the glucose residue in sucrose as a glucopyranose.
`The fructose residue must be a fructofuranose because periodate oxidation of
`sucrose consumes three moles of periodate, whereby one mole of methanoic
`acid and one mole of a tetraaldehyde
`are formed. On bromine oxidation
`
`

`

`20-68 Structure of Sucrose
`
`931
`
`H0:02C
`o
`
`0
`' HO
`:
`OH :
`
`CH20H
`
`8
`310 -
`--±-.
`
`rCH20H
`
`0~H0:J(2C
`
`O~
`
`CHO
`+
`HC02H
`
`0
`
`CHO
`
`CH20H
`CHO CHO
`
`,
`
`OH
`
`sucrose
`
`1(CH3J.S04' OH8
`
`C~HOCH2 0
`o
`CH30
`
`CH20CH3
`
`OCH3
`
`OCH3
`
`1H30(±), H20
`
`C02H
`
`p" H0:J(2
`
`tetraaldehyde
`[s-, H20
`
`il-o
`
`COH
`2
`
`C
`
`0
`
`)H'OH
`C02H C02H
`
`1
`
`(H,OH) + tetra-O-methyl-o -fructose
`(not characterized at the
`time this experiment
`was carried out)
`
`OCH3
`2,3,4,6-tetra-0-methyl-
`o-glucose
`
`C02HI
`H-C-OH
`I
`CH20H
`o -g Iyceric
`acid
`
`+ CHO
`I
`C02H
`9 Iyoxyl ic
`acid
`
`CH20H
`I
`+C=OI
`C02H
`hydroxy-
`pyruvic
`acid
`
`C02H
`I
`+ H-C-OHI
`
`CH20H
`o-glyceric
`acid
`
`Figure 20-5 Summary of reactions used to establish the ring structure
`of sucrose
`
`followed by acid hydrolysis, the tetraaldehyde gives 3-hydroxy-2-oxopropanoic
`acid (hydroxypyruvic
`acid, HOCH2COC02H),
`oxoethanoic acid (glyoxylic
`acid, OCHCOzH), and D-glyceric acid (HOCHzCHOHCOzH).
`Sucrose there-
`fore has structure 24, and this structure was confirmed by synthesis
`(R.
`Lemieux in 1953).
`
`Exercise 20-10 Draw Haworth and conformational
`disaccharides:
`a. 6-0-,B-D-glucopyranosyl-,B-D-glucopyranose
`b. 4-0-,B-D-galactopyranosyl-a-D-glucopyranose
`c. 4-0-,B-D-xylopyranosyl-,B-L-arabinopyranose
`d. 6-0-a-D-galactopyranosyl-,B-D-fructofuranose
`
`structures for each of the following
`
`

`

`932
`
`Exercise 20-11 Show how the structure
`following:
`(1) The sugar
`
`is hydrolyzed by yeast (t-o-glucosidase
`
`to o-glucose.
`
`20 Carbohydrates
`
`of maltose
`
`can be deduced
`
`from the
`
`(2) Maltose mutarotates and forms a phenylosazone.
`
`(3) Methylation with dimethyl
`gives 2,3,4,6-tetra-O-methyl-o
`
`by acid hydrolysis
`sulfate in basic solution followed
`-g lucopyranose
`and 2,3,6-tri-O-methyl-o-g
`lucose.
`
`gives
`and hydrolysis
`by methylation
`of maltose followed
`(4) Bromine oxidation
`2,3,4,6-tetra-O-methyl-o-glucopyranose
`and a tetramethyl-o-gluconic
`acid, which
`readily forms a y-Iactone.
`
`Exercise 20-12 Cellobiose
`to enzymatic
`differs from maltose only in its behavior
`It is hydrolyzed by yeast {3-o-glucosidase. What
`hydrolysis.
`is its structure?
`
`Exercise
`following:
`is hydrolyzed
`(1) The sugar
`o-glucose and o-galactose.
`
`20-13 Show how the structure
`
`of
`
`lactose may be deduced
`
`from the
`
`by {3-o-galactosidase
`
`to a mixture of equal parts of
`
`(2) Lactose mutarotates and forms a phenylosazone.
`
`(3) Bromine oxidation of
`o-galactose.
`
`lactose followed by hydrolysis gives o-gluconic
`
`acid and
`
`and
`lactose gives a tetra-O-methyl-o-galactose
`of
`and hydrolysis
`(4) Methylation
`2,3,6-tri-O-methyl-o-glucose.
`The same galactose derivative can be obtained from the
`methylation and hydrolysis of o-galactopyranose.
`
`yields
`and hydrolysis
`by methylation
`lactose followed
`of
`(5) Bromine oxidation
`tetra-O-methyl-1 ,4-g luconolactone
`and the same galactose derivative as in (4).
`
`20-7 POLYSACCHARIDES
`
`20-7A Cellulose
`the polysaccharide
`in the cell walls of plants contains
`The
`fibrous
`tissue
`cellulose, which consists of long chains of glucose units, each of which is con-
`nected by a f3-glucoside
`link to the C4 hydroxyl of another glucose as in the
`
`

`

`20-7 Polysaccharides
`
`disaccharide cellobiose (i.e., (3-1,4):
`
`'(
`
`/0
`
`~
`4
`
`0
`
`1l~~i
`f3;0
`i
`:
`i
`,
`
`4.
`
`cellobiose unit
`
`f3 a 4
`1
`
`>,
`
`~!
`1
`13 0: 4
`l
`,
`
`0:
`
`cellulose structure
`(the hydroxyls on the rings are omitted for clarity)
`
`933
`
`0
`
`0<,
`
`1
`
`Indeed, enzymatic hydrolysis of cellulose leads to cellobiose. The molecular
`weight of cellulose varies with the source but is usually high. Cotton cellulose
`appears to have about 3000 glucose units per molecule.
`The natural
`fibers obtained from cotton, wood,
`flax, hemp, and jute all are
`cellulose fibers and serve as raw materials for the textile and paper industries.
`In addition to its use as a natural fiber and in those industries that depend on
`wood as a construction material, cellulose is used to make cellulose acetate
`(for making rayon acetate yarn, photographic film, and cellulose acetate butyrate
`plastics), nitric acid esters (gun cotton and celluloid"), and cellulose xanthate
`(for making viscose rayon fibers). The process by which viscose rayon is manu-
`factured involves converting wood pulp or cotton linters into cellulose xanthate
`by reaction with carbon disulfide and sodium hydroxide:
`
`s
`I
`II
`-C-O-C-S8NaG:>
`I
`
`cellulose
`
`xanthate
`
`The length of the chains of the cellulose decreases about 300 monomer units
`in this process. At
`this point,
`the cellulose is regenerated in the form of fine
`filaments by forcing the xanthate solution through a spinneret
`into an acid bath:
`
`S
`II
`
`I
`-C-O-C-S8
`I
`
`HG:>
`-->
`
`I
`-C-OH
`I
`
`+CSz
`
`7Celluloid, one of the first plastics,
`plasticized with camphor.
`
`is partially nitrated cellulose (known as pyroxylin)
`
`