S. Ranganathan and D. Ranganathan lndion Institute of Technology Konpur mso16,U. P.,
The Appreciation of Molecular
I
Transformation in Organic Chemistry Part I: Analysis of a fascinating problem
This appears to he a n unusual t r a n ~ f o r m a t i o n !How~ ever we will demonstrate t h a t if one were to analyze this change taking into consideration all the steps, all the alternatives i n each of the steps, and pursue the process along the most logical direction, then it should he possible (II) change is a predictable one and t o state thac the (I) t h a t (I) could he considered a s a logical starting material for t h e preparation of (II)! Indeed the human mind performs a n analysis precisely a s outlined above in the rationalization of processes like the (I) (II) change.
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A decision a s t o the most logical site must he based on
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p K , estimates? Site (a) has a n estimated pK, of 20,3 site (b) > 50, (c) 30, and (d) 40. The pK. of t-BuOH is around 20. Therefore the most appropriate location for removing the proton should he (a)
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Step l RC-H
+ i-BuO * RC- + I-BuOH
T h e available sites in (I) for proton abstraction are
This is a two-part article. Part I1 will appear in the August issue. All structures and footnotes are numbered consecutively thmughoutthe article. The article is taken from Chapters I and IJ of a book by the authors. The other chapters deal with a brilliant piece of detective work (yon Richter reaction), fascinating ways of nature (ATP-imidazole cycle), the humorous side of bond-making and bond-breaking, diamonds, fascinating ways to make them, the esoteric no mechanism reactions, and the Woodward-Hoffmann rules. For information about copies, please write the authors. The hook is sponsored by the EDC, IITK, Kanpur.
I
Step It
Intermediate ( I n ) could add t o the carhonyl either through the oxygen or carbon t o give, respectively, (IV) and (V)'
'Yates, P., and Anderson, C. D., J. Amer. Chem. Soe., 85, 2937 (1963). 2Proton acids could be arranged according to their tendency for dissociation in a common solvent such as water
A small number for pK, indicates a stmng acid (HA) and a weak conjugate base (A-). In general, for a gainful reaction involving an acid-base pair, such as: AH + B- = BH + A the condition is pK, AH 5 pK. BH. $The adjacent carhonyl function greatly Lowen the pK.. The hetemlytic rupture of the C-H hond is greatly facilitated by the formationofthe enolate system. 4The anion (m) could in principle, undergo intermolecular addition with another molecule. Entropy factors would, however, greatly pmmote an intramolecular addition as envisaged here. These factors are responsible for the generation of even high energy intermediates. T h e rule follows directly from the requirement that the two p Lobes should he aliened wrallel for the aeneration of a double . bond. 6A mugh parallel hetween nucleophilic strength and base strength could be assumed.
v
IV
The intermediate (IV) should he discarded since it violates the "Bredt" rule. In the simplest description, the Bredt rule states t h a t all the six atoms t h a t comprise a double hond should lie i n one plane5
the two valencies on one of the carbons are nearly In (N) perpendicular t o the other two on the adjacent carbon, Step II therefore is
The process 1eading.b (Vm)would be discarded immediatelv since i t involves the imoossible generation of a much stroiger base @K, > 50) fidm a much weaker base @K, 20) that is resent in (W).B The ( W ) (IX)change is an example o> a reverse aldolcondensation.
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0
Step III IX
Step VI
The above is an example of a fundamental precept in organic chemistry. A carbon center to which more than one electronegative atoms are attached is inherently unstable. This theorem can be further exemplified
xNH' - + X >NH
X
-
P
+ 4\-
/
X
-
Y-C-
/
\.
+ x-
This is a simple S N displacement! ~ The displacement could, in principle take place either through oxygen or carbon to give, respectively, (X) or (XI) HX
CI. OR. NH,. CN
The behavior of ketone-hydrates, semi-ketals, cyano-hydrins, chlorohydrins, and a variety of other systems follows directly from this simple rule. The intermediate (V) would then be expected to be transformed to either the starting material (Ill)or (VI)
The tighter binding of the enolate oxygen with the counter ion K+ makes the carbon center more suitable for a nucleophilic attack thus leading to (XI)? Step lV
There is only one way to proceed in the forward direction This is the first irreversible step in the whole sequence! The entire (I) -r (II)change could be viewed as an elaborate maneuver whereby KOt-Bu @K, 20) is quenched to a carboxylate ion ( p K , = 5)! As expected, intermediate (XI) is a highly unreactive species and waits for the protonation step to give (11).
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VI
Step v
VII n
- "v6-" "'
Step VII
The intermediate ( W ) , based on the theorem stated above, should fragment. The three possibilities leading to, respectively, (VI), (WI),and (IX) are illustrated below
Phu6-"
0
0
XI
11
Integrated Mechanism
7This follows directly from Pearson's mncept of soft and hard acids and bases (Pearson, R. G., J. Arner. Chem. Sac., 85, 3533 (1963);89,1827 (1967)). VokKne 52,
*7,
JLJ)r 1975 / 425
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The understanding of the (I) (11) change was based neither on intuition nor on "arrow pushing," but was the outcome of a logical analysis that made use of a number of fundamental principles related to bond-forming and bond-breaking. Such rationalization is required in the understanding of any process where a number of bonds are broken and made. Part I1 of this article demonstrates the practical utility of an analysis such as outlined in the present article.
426 / Jwmal of Chemical Education
