Chemistry 125: Lecture 24

Determining Chemical Structure by Isomer Counting

(1869) Half a century before direct experimental observation became possible, most structures

of organic molecules were assigned by inspired guessing based on plausibility. But

Wilhelm Koerner developed a strictly logical system for proving the structure of benzene

and its derivatives based on isomer counting and chemical transformation. His proof that

the six hydrogen positions in benzene are equivalent is the outstanding example of this

chemical logic but was widely ignored because, in Palermo, he was far from the seats of

chemical authority.Synchronize when the speaker finishes saying

“…from Lavoisier to Berzelius and Gay-Lussac.” Synchrony can be adjusted by using the pause(||) and run(>) controls.

For copyright notice see final page of this file

Genealogy Top

Benzene & Molecular Structure

Faraday isolates “bicarburet of hydrogen” ("C2H", actually C6H6) from “gas oil”,

a 1 gal. per 1000 cu. ft. by-product from preparation of illuminating gas.

1825

1833s Mitscherlich names it benzine

phainein, to bring light)

1841 French name C6H5OH "acide phénique”We call it phenol, and C6H5 phenyl (Ph or )

Simplest of the "aromatic" compounds

from gum benzoin (via benzoic acid)

from luban jawi(“frankincense of java”, Arabic)

How did Kekulé know Benzene is Hexagonal?On the Constitution of Aromatic Compounds (1866)

1) All aromatic compounds, even the simplest, are significantly richer in carbon than analogous compounds from the class of fatty substances.

2) For aromatic compounds, as for fatty compounds, there are numerous homologous substances; i.e. those whose compositions differ by n CH2.

3) The simplest aromatic compounds contain at least six carbon atoms.4) All reaction products from aromatic substances show a certain family similarity, constituting the group of "aromatic" compounds. More vigorous reaction can remove part of the carbon, but the major product contains at least six carbon atoms... Decomposition stops at this point, unless there is complete destruction of the organic group.

Did he just take a wild guess? (based on tetravalence)

1866

Kekulé’s Isomer Counting

1865

Isomer CountElukek (arabic f or hexagon)

Isomer Count Might Distinguish Among Dewar's 2D Benzene Structures

Mono: 3

A A

B B

C C

Di: 9

A A

B B

A A

Mono: 2

Di: 6

Mono: 1 Di:

Mono: 6

Di:

54321

4

15

Isomer Numbers for“Dewar's” Benzene Structures in 3D

C

C

C

CC

C

H H

HH

H

H

also"Prismane"

or

"LadenburgBenzene"

"Dewar Benzene"

C

C

H H

C

C

C C

H HHH

C C

CC

C

CHH

H H

H H

C C

C

C

C C

H

H

H

H

H

H

C C

CC

CC

HH

H H

HH

C C

C C

CC

HH

H HHH

C

C

H H

C

C

CC

H

HH

H

TRY ISOMER COUNTS IN 3-DIMENSIONS FOR MONDAY

planar(2D)

Structure from Synthesis (Kekulé, 1867)

3 Acetone Mesitylene

Dewar had sent Kekulé brass-strip models in 1866.

-H2O

-H2O-H2O

There should be a methyl on every

other ring carbon!

Kekulé’sLectureModel

ofBenzene

Tetrahedral(not square!)

carbons

Ghent (1865)

Kekulé

rheumatism

Koerner

PalermoSicily

Liberated in 1860after 2700 yearsof occupation by

PhoeniciansRomansVandals

ByzantinesArabs

NormansSwabiansAngevinsAragoneseHabsburgsBourbons

Garibaldi

Palermo

Laboratory ofStanislao

Cannizzaro

In 1860 hehelped bothGaribaldi

&

Avogadro(Gay-Lussac)

Revolutionaries

but in his way cautious…

Cannizzaro on Chemistry Teaching (1872)

Above all we should take care that the pupils do not form to themselves any mechanical or geometrical conception of the cause and effects of the quantivalence of atoms; they must be frequently reminded that chemical facts neither prove nor disprove anything relating to the size, form, continuity, distance, relative disposition, &c., &c., of the atoms.

Cannizzaro on Chemistry Teaching (1872)

If we are sometimes obliged to speak of the relative positions of the atoms in the molecules, and even to give graphic representations of these positions, we must hasten to remark that these figures are nothing but artifices of the mind, intended to represent to the sight that which in reality we perceive only through the veil of transformations; but that we do not really know what it is that corresponds to that which we call position, either in space, or in the mutual actions of different portions of matter.

Facts Serving to Determine Chemical Position in Aromatic Substances

Wilhelm Koerner (1869) The dogma of the impossibility of determining the atomic constitution of substances, which until recently was advocated with such fervor by the most able chemists, is beginning to be abandoned and forgotten; and one can predict that the day is not far in the future when a sufficient collection of facts will permit determination of the internal architecture of molecules. A series of experiments directed toward such a goal is the object of this paper…

(paper introduced and warmly endorsed by Cannizzaro!)

Add a third (identical) substituentand count isomers.

Establishes identity of both di- and tri-substituted benzenes,

Koerner : Which is which?

if the 6 substituent positions in benzene are equivalent.Proven by Koerner in 1869.

ortho meta paraKoerner

used thesesame names,

but differently

(less deserving individuals weremore influential)

Are the Four Valences of C Equivalent?

Only one isomer of methyl chloride is known!

Is this proof ?

Evidence?

C Cor

Koerner’s Assumptions (1867)

(2) Experimental Distinguishability

“…most of the demonstrations are based on establishing the identity or difference of

several substances of the same composition,but obtained by different reactions…”

(1) Direct Replacement

“If one grants that in simple transformation the new substituent assumes the position of

the element displaced…”

(parsimonious, but rearrangements do sometimes occur)

(depends on experimental skill - crystals are best)Ac. Salicilico

(Koerner)

2,6-Dinitro-3-bromo-1-toluene

(Koerner)

Graebe1866

HCl

for example

Koerner Equivalence Proof (1869)

The difference among the three isomers is not in the position of OH.

PhenolC6H5OH

Graebe1866

HCl

Salicylic Acid Hydroxybenzoic Acid Parahydroxybenzoic Acid

Three known isomers of C6H4 OH COOH

Anisic AcidC6H4 OCH3 COOH

Methyl AnisateC6H4 OCH3 COOCH3 Graebe

1) Na 2) CO2

BromoanisoleC6H4 OCH3 Br

Koerner

COMMON PRODUCT

thus not like these three isomers of

Dewar’s OH

OH

OH

The site(s) occupied by OH are either identical or equivalent.(since the O survives in identical compounds)

HOOC

HOOC

OH

HOOC

but maybe like these three isomers of

Dewar’s HO

HOOC

Koerner Equivalence Proof (cont)

The three isomers do not differ because of the absolute position of COOH.

Salicylic Acid Hydroxybenzoic Acid Parahydroxybenzoic Acid

Same three isomers of C6H4 OH COOH

PCl5

1) Na/Hg

2) H2O

C6H4 Cl COOHKoerner ?

Benzoic AcidC6H5 COOH

Beilstein1864

1) Na/Hg

2) H2O

PCl5

C6H4 Cl COOH

Koerner?

PCl5?

C6H4 Cl COOH

1) Na/Hg

2) H2O

Thus the 3 sites of COOH are equivalent Hx = Hy = Hz

as would be the case with

Dewar’s

for example

XY

Z

(but they differ regarding H)

Call OH position H

Koerner Equivalence Proof (cont)

Replace NH2 by Br

Change NO2 to NH2

BromochlorobenzeneC6H4 BrCly

Replace NH2 by Cl

BromochlorobenzeneC6H4 ClBry

Replace NH2 by Cl

Change NO2 to NH2

Replace NH2 by Br

“Arppe’s Nitroaniline”C6H4 NH2

NO2y

So there are at least four equivalent substituent positionsH = Hy = Hx = Hz

These compounds are identical

Hydroxybenzoic AcidC6H4 OHCOOHy

/ y established by interconversion with hydroxybenzoic acidas would be the case with

Dewar’s

for example

XY

Z

NOT

for example(which cannot be superimposed)

Br

Cly

Cl

Bry

Koerner Equivalence Proof (cont)

C6H4OHAzxO2

C6H4OHBrx

Start with known“meta” substituentsas in salicylic acid

C6H2 AzO2 • Br • OH • AzxO2

(The new substituents are in unknown positions but we know and x)

Br2

KNO3 H2SO4

“bromonitro-metanitrophenol”

NaNO3 H2SO4

“binitro-metabromophenol”

C6H2 AzO2 • AzO2 • OH • Brx

Thus there must be two positions, x and x’ that have the same relationship to (not the y or z relationship). The products are both C6H2 AzO2 • Brx’ • OH • AzxO2

So there are at least five equivalent substituent positionsH = Hx’ = Hx = Hy = Hz

The two compounds are identical!

Now none of Dewar’s models work, although perfect hexagon and equilateral

triangular prism will still do. (Note: Koerner used “meta” differently from how we do.)

Koerner’s Proof Note that the the proof so far is abstract and makes no reference to a geometric model such as:

Koerner’s argument for equivalence of the sixth substituentposition in benzene was faulty, because it hinged in a subtleway on a hidden assumption that benzene was hexagonal.

It is possible, using group theory, to construct a logically rigorous argument on the basis of Koerner’s evidence to show that all six positions must be equivalent, so he was right in his intuition and his conclusion.

or

Koerner deserves enormous credit for formulating the logic of the first true structural proof in organic chemistry.

How many isomers of C2H4Br2?Rubber tubing joining actual 3D tetrahedral

models?

"three isomers of C2H4Br2, supposing that they actually exist, can easily be explained without assuming any difference among the

four valence of the carbon atom." Paternó (1869)

“It is superfluous to say that this is only a way of representing the facts, and

that all these ideas need to be tested experimentally.”

End of Lecture 24Oct. 31, 2008

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