5 Some Recent Developments in Ipso Nitration R O G E R C . H A H N , H I D E T O S H O S E N J I , and D A V I D L . S T R A C K
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Department of Chemistry, Syracuse University, Syracuse, Ν. Y. 13210
The recent r e a l i z a t i o n that ipso (1) e l e c t r o p h i l i c attack i s significant for a number of arenes, (2) some of them commercially important, has opened the door to a new area of exploration, par t i c u l a r l y for the organic chemist. The work to be described here is intended to give a glimpse of the potential existing for mech anistic and synthetic studies in this area. In p a r t i c u l a r , d i - and polyalkylbenzenes having alkyl groups ortho or para to each other, so that mutual activation toward electrophilic attack can occur, may undergo from 25% to as much as 80% ipso attack in n i t r a t i o n reactions. (2,3) As pointed out by Professor Myhre, the ipso nitroarenium ions thus formed can undergo a variety of further processes depending on the nature of the substrate and reaction conditions. (4) One of these reactions is shown below.
In the absence of a trapping nucleophile, 1, can undergo a nitro s h i f t to allow ultimate formation of a "normal" nitrodeprotonation product. {5) For nitrations in non-trapping media, this pathway cannot be distinguished from direct nitrodeprotonation. It becomes necessary, therefore, to determine the extent and consequences of ipso attack before true positional s e l e c t i v i t i e s can be established for this type of substrate.
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Albright and Hanson; Industrial and Laboratory Nitrations ACS Symposium Series; American Chemical Society: Washington, DC, 1976.
INDUSTRIAL AND LABORATORY NITRATIONS
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The accumulating weight of indirect evidence indicates that i n i t i a l positional s e l e c t i v i t y of most nitrating agents i s nearly the same in a variety of media. (5J One approach to measuring the extent of ipso attack (in n i t r a t i o n ) , then, i s to perform the nitration in nucleophilic medium; under these conditions, the ipso nitroarenium ion i s trapped by para nucleophilic addition (below). The amount of 1,4-diene formed i s taken to represent the minimum amount of ipso attack occurring. Diene can be assayed
conveniently by pmr analysis. We began fo look for substrates for which ipso attack was l i k e l y , but which had not been f u l l y explored. A promising example, £-cymene, was found in one of the many pioneering nitration studies by Professor 01 ah. In 1964, 01 ah and Kuhn reported (6) that N 0 BF/," n i t r a t i o n of j)-cymene (in sulfolane, a non-nucleop h i l i c medium) gave the product distribution shown below. Form2
+
ation of £ - n i t r o t o l u e n e was shown at that time to arise from ipso attack at C-4, but attack at C-l also seemed l i k e l y to us, in l i g h t of more recent work. Since nitrodemethylation i s very d i f f i c u l t , a nitro group i n i t i a l l y attached at C-l could simply migrate to C-2; subsequent deprotonation would give a normalappearing product. When £-cymene was nitrated in the nucleophilic system AcON0 /Ac 0, the product distribution was indeed different (below\ (3c) Subjection of the dienes to strong acid solvolysis gave exclusively 2-nitro-j)-cymene; the total of 82% 2-nitro isomer thus obtained (41% direct + 41% ipso and solvolytic s h i f t ) nearly matched the 85% reported for N0 BF*~ n i t r a t i o n . These results indicate that the previously unsuspected methyl position actually is the most reactive position toward n i t r a t i o n in jD-cymene. It was noted also that nitrodeisopropylation could not be avoided in Ac 0; no evidence was found for existence of a species contain2
2
+ 2
2
Albright and Hanson; Industrial and Laboratory Nitrations ACS Symposium Series; American Chemical Society: Washington, DC, 1976.
5.
HAHN ET AL.
Recent
in Ipso
Developments
Nitration
97
OAc AcONO: Ac 0,O
c
2
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41%y
N0
2
ing geminal nitro and isopropyl groups. The ortho isomer of cymene next attracted our attention; the extensive study by Olah and Kuhn reported 41% nitrodeisopropylation of this substrate by N0 BF*~. We nitrated o-cymene both with Ac0N0 /Ac 0 and HN0 /H S0*; results from a l l three media are assembled in Table I. The differences in detected ipso attack s t i l l are under study, and w i l l not be discussed further 2
2
Table I.
2
3
2
Nitration of o-Cymene with Various Agents
Agent
3-N0
2
6-N0
2
Ipso
0.5
11
40.5
HN0 /H S0
