Third Edition
`
`ORGANIC
`CHEMISTRY
`
`ROBERT THORNTON MORRISON
`
`ROBERT NEILSON BOYD
`
`New York University
`
`·1
`I
`
`j,
`
`ALLYN AND BACON, INC.
`
`BOSTON
`LONDON
`SYDNEY
`TORONTO
`
`Illumina Ex. 1114
`IPR Petition - USP 10,435,742
`
`

`

`© COPYRIGHT 197} BY ALLYN AND BACON, INC.
`© COPYRIGHT 1966 BY ALLYN AND BACON, INC.
`© COPYRIGHT 1959 BY ALLYN AND BACON, INC.
`470 ATLANTIC AVENUE, BOSTON
`
`ALL RIGHTS RESERVED
`
`No part of the material protected by this copyright notice may be
`reprod11ced or utilized in any form or by any means, electronic or
`mechanical, including photocopying_, recording, or by any informa(cid:173)
`tional storage and retrieval system, witho11t written permission
`from the copyright owner.
`
`LIBRARY OF CONGRESS CATALOG CARD NUMBER: 72-91904
`
`ISBN 0-205-03239-7
`
`Tenth printing ........... July, 1976
`
`PRINTED IN THE UNITED STATES OF AMERICA
`
`

`

`208
`
`ALKENES II. REACTIONS OF CARBON-CARBON DOUBLE BOND CHAP, 6
`
`Hydroxylation with permanganate is carried out by stirring together at room
`temperature the alkene and the aqueous permanganate solution: either ,neutral(cid:173)
`the reaction produces oH- -or,, better, slightly alkaline. Heat and the addition
`of acid are avoided,, since these more vigorous conditions promote further oxida(cid:173)
`tion of the glycol, with cleavage of the carbon..:..carbon double bond (Sec. 6.29).
`Hydroxylation with peroxyformic acid is carried out by allowing the alkene
`to stand with a mixture of hydrogen peroxide and formic acid, HCOOH, for a few
`hours, and then heating the product with water to hydrolyze certain intermediate
`compounds.
`A glycol is frequently named by adding the word glycol to the name of the
`alkene from which it is formed. For example:
`3CH2=CH2 + 2KMnO4 + AH20
`Ethylene
`
`3CH2-CH2 + 2MnO2 + 2KOH
`I
`I
`,
`OH OH
`·
`Ethylene glycol
`
`CHr..,.CH=CH2
`Propylene
`
`HzO
`
`CH3-CH_:_CH2
`•
`I
`· I
`OH OH
`...
`Propylene glycol
`
`Hydroxylation of alkenes is the most important method fot the synthesis of
`glycols. Moreover, oxidation by permanganate is the basis of a very useful analy~
`tical test known as the Baeyer test (Sec. 6.30).
`(We shall discuss the stereochemistry and mechanism of glycol formation i11
`Sec. 17.12.)
`
`6.21 Substitution by halogen. Allylic hydrogen
`So far in our discussion of alkenes, we· have concentrated on the carbon:...
`carbon double bond, and on the addition reactions that take place there. Now
`let us turn to the alkyl groups that are present in .most alkene mo,lecules.
`. .
`Since these alkyl groups have the alkane structure, they should undergo'·
`alkane reactions, for example, substitution by halog~n. But an alkene molecµlf
`presents two sites where halogen can attack, the double bond and the alkyl group$:
`Can we direct the attack to just one of these sites? The answer is yes, by oi/t
`. ..
`choice of experimental conditions.
`. We know that alkanes undergo substitution by halogen at high temperature{
`or under' the influence of ultraviolet light,' and generally in the gas phase: conditions
`that favor formation of free radicals. We know that alkenes undergo addition of
`halogen at low temperatures and in the absence of light, and generally in the liqui4
`phase: conditions that favor ionic reactions, or at least do not aid formation o
`radicals.
`·
`·
`·
`
`I
`I
`I
`-C=C-C-
`.
`I
`8-; 8+)
`\I
`x-x
`\ .. x.
`Free-radical
`Ionic
`attack
`attack
`Substitution
`Addition
`
`

`

`SEC, 6,21
`
`SUBSTITUTION BY HALOGEN. ALLYLJC HYDROGEN
`
`209
`
`If we wish to direct the attack of halogen to the alkyl portion of an alkene
`molecule, then, we choose conditions that are favorable for the free-radical reaction
`and unfavorable for the ionic reaction. Chemists of the Shell Development Com(cid:173)
`pany found that, at a temperature of 500-600°, a mixture of gaseous propylene
`and chlorine yields chiefly the substitution product, 3-chloro-1-propene, known as
`ally! chloride (CH2=CH-CH2- = allyl). Bromine behaves similarly.
`
`CH3-CH=CH2
`Propylene
`
`low temp.
`CCl 4 soln.
`
`CH3-CH-CH2
`I
`I
`Cl
`Cl
`1,2-Dichloropropane
`Propylene chloride
`
`Ionic:
`addition
`
`500-600°
`gas phase
`
`Cl-CH2-CH=CH2 + HCl
`3-Chloro-1-propene
`Ally! chloride
`
`Free-radical:
`substitution
`
`In view of Secs. 6.17-6.18, we might wonder why a halogen atom does not add
`to a double bond, instead of abstracting a hydrogen atom. H. C. Brown (of Purdue
`University) has suggested that the halogen atom does add but, at high temperatures,
`is expelled before the second step of free-radical addition can occur.
`
`Free-radical addition
`CH3-CH-CH2X + X,
`
`*
`
`Free-radical substitution
`X-CH2-CH=CH2 + X•
`Ally! halide
`Actual product at
`high temperature or
`low halogen concentration
`(X = Cl, Br)
`
`<;:H2-CH=CH2
`Ally! radical
`+
`HX
`
`Consistent with Brown's explanation is the finding that low concentration of
`halogen can be used instead of high temperature to favor substitution over (free(cid:173)
`radical) addition. Addition of the halogen atom gives radical I, which falls apart
`(to regenerate the starting material) if the temperature is high or if it does not
`soon encounter a halogen molecule to complete the addition. The ally! radical,
`on the other hand, once formed, has little option but to wait for a halogen molecule,
`whatever the temperature or however low the halogen concentration.
`
`The compound N-bromosuccinimide (NBS) is a reagent used for the specific
`purpose of brominating a!kenes at the al!ylic position; NBS functions simply by
`
`

`

`210
`
`ALKENES II. l~EACTIONS OF CARBON-CARBON DOUBLE BOND CHAP, 6
`
`providing a constant, low concentration of bromine. A~ each molecule of HBr is
`formed by the halogenation, NBS converts it into a molecule of Br2 •
`
`HBr
`
`0
`II
`.
`H2C...---C\
`+
`I N-Br
`H2C'-c'
`II
`0
`N-Bromosuccinimide
`(NBS)
`
`+
`
`0
`II
`H c...---C,
`2
`\ N-H
`H2C--c'
`II
`0
`Succinimide
`
`· 6.22 Orientation and reactivity in substitution.
`Thus alkenes undergo substitution by halogen in exactly the same way as do
`alkanes. Furthermore, just as the alkyl groups affect the reactivity of the double
`bond toward addition, so the double bond affects the reactivity of the alkyl groups
`towar.d substitution.
`·
`·
`·
`Halogenation of many alkenes has shown that: (a5 hydrogens attached to·
`doubly-bonded carbons undergo very little substitution; and- (b) hydrogens at(cid:173)
`tached to carbons adjacent to doubly-bonded carbons are particularly reactive'
`toward ~ubstitution. Examination of reactions which i1ivolve attack not only/
`by halogen atcims but by other free radicals as well has shown that this is a general
`rule: hydrogens attached to doubly-bonded carbons, known as vinylic hydrogens,·
`are harder to abstract ~han ordinary primary hydrogens; hydrogens attached to a
`... carb.on atqm adjacent to a double bond, known as allylic hydrogens; are even)
`·· easier to abstract than tertiary hydrogens.
`·
`
`,1
`
`'
`
`· · ~H}· Vinylic 'hydrogen: hard to abstract
`
`·
`C--'-H
`I
`-C-H Allylic hydrogen: easy to abstract
`I ..:
`
`We can now expand the reactivity sequence of Sec. 3.23.
`
`'
`
`'
`
`Ease of abstraction
`of hydrogen. atoms
`
`allylic > 3° > 2° > 1 ° > CH4, vinylic
`
`Substitution in alkenes seems to proceed by the sanie mechanism as substit1,i:
`tion in alkanes. For example:
`"
`
`'
`Cl·
`CH2=CH-H --J>- CH2=CH·
`· Ethylene
`Vinyl radical .
`
`CH2-CH-Cl
`Vinyl chloride
`
`CH2=CH-CH2--:-H
`Propylene
`
`Cl· -~
`
`CH2=CH-CH2·
`Allyl radical
`
`·
`Ch
`---=-,,- CH2_:_CH-CH2Cl
`Allyl chlodde
`
`Evidently the vinylradical is formed very slowly and the allyl radical is formed
`rapidly. We can now expand the sequence of Sec. 3.25.
`
`