CONFIMATIONAL ANALYSIS OF BORNANES

(OR)
CONFORMATIONS OF BORNANES
Stereo chemical Restrictions:
The Bredt Rule:
The molecule of camphor has two asymmetric carbon atoms and yet there is
only one dl pair. The reason for this, readily understandable upon inspection of a
model, is that the bridge must necessarily be cis and therefore the configurations of
the two starred carbons are not independent. A similar situation exists in many other
bridged systems.
For example:

As a result, the number of stereoisomers is always one-half of what it would be in

the absence of this restriction. Thus the alcohol system corresponding to camphor
presents two cis -bridged dl pairs.
Borneol and Iso Borneol, instead of the four dl pairs present in other systems
with three asymmetric carbons. If the bridge were large enough, it ought to be
possible to obtain the trans-bridged isomer also; this appears to have been achieved
in the system

Another restriction in bridged systems is given by the Bredt rule which states
that in small bridged systems one cannot, for steric reasons, have a double bond at
the bridgehead position. Demonstrations of the Bredt rule are the failure of bromo
camphor to eliminate hydrogen bromide.

In the presence of a base and the failure of the unsaturated analog of

camphoric acid to form an anhydride. (Under forcing conditions, the anhydride
forms with concomitant migration of the double bond to a non-bridgehead position.)
Other interesting examples are:

Fig: cis and tarns isomers

Bicycloctane-2,6-dione does not show the acidic properties of a 1,3-diketone

(the anion is incapable of resonance), and camphenonic and Ketophonic acids,
although they are - Keto acids, do not readily decarboxylated, because they cannot
achieved the required enolic transition state. The limitations of the Bredt rule have
been elegantly demonstrated by Prelog and coworkers.

Ring closure of the diketone may give rise to either the fused-ring system 'A'
or the bridged-ring system 'B'. When n= 4, only the fused system 'A' is formed; when
n =5, the bridged system B is formed along with A; and when n = 6, only 'B' results.

Fig: Further Examples of Bredt Rule

The Bredt rule no longer applies to the [5, 3, 1] system. It might be noted that
this system contain a bridge with an eight-membered ring and that eight-membered
ring is also the smallest ring that can accommodate a trans double bond.

A
N= 4

65%

N=5

32%

N=6

NONE

(OR)

B
N= 4

NONE

N=5

14%

N=6

76%

Fig: Limitations of Bredts Rule

The stereo chemical restrictions in decarboxylations of - keto acids seem to

somewhat less severe. Whereas camphenonic acid and its isomer, keto-pinic acid
which contain the [2,2,1] system, as well as similar keto acid containing the [2

,2 ,2] system, fail to decarboxylate, 2,6- diketo bycyclo [3,3,1] nonane -1,3,5,7
tetra carboxylic acid, 3,7- dimethyl ester can be decarboxylated by heating.

A similar acid (n=3) on the other hand, cannot be decarboxylated by heating

in quinoline to 2400, although the next higher homolog (n=4) is decarboxylated
under these conditions.
The difference may well lie in the fact that in A the carbonyl group is in the
three carbon bridge. But in B it is in one carbon bridge. It might be noted that the
bridged benzene derivatives also do not follow Bredts rule.

Some further reactions of the Norbornane System:

The Norbornane (bicyclo [2,2,1] heptane) system is probably the most
important because of its frequent occurrence in the bicyclic monoterpens and
because of its easy accessibility by the Diels- Alder reaction starting with cyclo
pentadiene. Some further reactions of this system will be considered in this reaction,
especially since the system is involved in some of the Wagher- Meerwein
rearrangements which make terpine chemistry so intriguing.

Fig: Limitations of Bredt Rule; Further examples

Norbornane despite its easy accessibility, is an appreciably strained system.

Model considerations indicate that, in addition to the usual bond opposition strain in
a cyclo hexane boat, the bridging of carbon 1 and 4 of the boat involved in the
construction of Norbornane introduces applicable angle strain.

10

Comparison of the heats of combustion of the 2-Ketones derived from

Norbornane and its next higher homolog, bicyclo [2, 2, 2] octane suggests that the
extra angle strain in the Norbornane system amounts to about 6.3 K Cal/ Mole.
Norbornylene is even more strained as evidence by its high heat of
hydrogenation ca. 33 K Cal/ Mole Vs a normal value of about 26 to 28 K Cal / Mole
and a value of Ca 28 K Cal/ Mole for bicyclo [2, 2, 2] octane. Its tendency to undergo
a reverse Diels Alder reaction upon heating.
Its ready reaction with phenyl azide to give a dihydrotriazole, its ready
reaction to Norbornane by means of lithium and ethyl amine, and its ability to act as
a dienophile in the Diels Alder reaction.
It shows an evidence for an un usually reactive double bond. Norbornadiene
is also quite strained, as evidenced by its heat of hydrogenation which averages 34
K Cal/ Mole per double bond. Upon heating, it rearranges the tropylidene. The
driving force in this process may be both loss of strain and gain of resonance energy.

Fig: Bicyclo [2,2,1] heptanone-2 and Bicyclo[2,2,2] octane-2.

11

Similar evidence for the strained nature of Norbornane system comes from
the rearrangement of the hydrogenated cyclopentadine dimer to adamentane.
Although the Diels- Alder synthesis of two substituted Norbornane usually produces
the endo isomer by kinetic control. This isomer is, in many cases, more sterically
crowded than the exo form. Thus exo-dicyclo-pentadine is formed by the
equilibration of the endo isomers upon heating.
By the same token the exo side of the norbornane system is more acceessible
to a wide variety of reagents than is the endo side. This point is exemplified by the
reduction of norcamphor to endo-norborneol (the hydrogen attacking the exo side of
the ketone) by a wide variety of reagents.

12

Fig: Norbornadiene- tropylidene rearrangement

Including molecular hydrogen in the presence of a catalyst and lithium

aluminum hydride (The lithium aluminum hydride reduction involves steric
approach control) another illustration is the oxidation of norbornylene to exonorbornadiol.
A different steric situation prevails in the camphane system where the exoface
of the molecule is strongly screened by the gem-dimethyl group at C7 As a result,
this system is generally approached by reagents from the endoside side.
catalytic hydrogenation of camphor gives largely (over 90%).

13

Thus

Fig: Approach on reagents on exo side of Norbornane system

Isoborneol which has the exo configuration (i.e., the hydrogen approaches
from the endo side). Reduction with lithium aluminum hydride (steric-approachcontrolled) similarly gives mostly isoborneol (90%) with but a little borneol (10%).

14

When - pyrine is treated in ether solution with gaseous hydrogen chloride

at 15c, an unstable addition product is formed which, upon warming, rearranges
to bornyl chloride. The rearrangement has been depicted as proceeding through a

Fig: pyrine hydrochloride bornyl chloride rearrangement

succession of classical carbonium ions, but this picture cannot be correct, since the
bornyl carbonium ion should give rise to a mixture of isoboryl and bornyl chloride.
From the stereochemical point of view, it would be attractive to postulate an attack
of chloride at the bridgehead.
Concerted with detachment of the bridge, there is an inversion at the
migration origin (the chlorine attacks itself from the rear whereas the bridge was in
front). However, kinetic work has shown that the rate of rearrangement is in sensitive
to added chloride ions, and therefore the concerted mechanism is untenable which

15

indicates that the rearrangement proceeds via a non-classical (or) mesomeric

carbonium ion intermediate between A & B.
This ion being in equilibrium with the starting material and being converted
slowly to the product in the rate-determining step which is acid catalyzed.

Camphene also adds hydrogen reversibly only under mild conditions. Upon
standing the hydrochloride rearranges to isobornyl chloride; this rearrangement also
involves inversion at the migration origin.

16

CONFORMATION ANALYSIS OF DECALINES

(OR)
CONFIRMATIONS OF DECALINES

The most important compound is the 6-6 compound decalin. It was

probably the demonstration by W.Huckel that decalin may exist in cis and trans
forms, of which the trans is the more stable, which first convinced chemists that
cyclohexane rings in decalin and elsewhere are puckered, as postulated by Sachse
and Mohr , and not planar, as postulated by Baeyer.
The counting of butane-gauche interactions in the decalins reveals three such
interactions in the cis isomers and none in the trans.Therefore the calculated
difference in heats of formation between the decalins is 3 x 0.9, or 2.7 kcal./mole.
The trans isomer being the more stable. The experimental value obtained either from
temperature dependence of the cis-decalin trans-decalin equilibrium (established at
elevated temperature over a platinum catalyst) or directly from the difference in
heats of combustion, 2.7 kcal./mole for the liquid phase or 3.1 kcal./mole for the
vapor, in good agreement with the calculated value.
Trans Decalin has a center of symmetry (midway between C9 and C10) and
is therefore an optically inactive molecule. It also has a two fold axis of symmetry

17

(passing horizontally between C2 and C3, C9 and C10, C7 and C6); thus its
symmetry number is 2. cis -Decalin is dissymmetric .
However, unlike trans - decalin- which is rigid because the ring fusion can
only be through e,e, not through a,a bondsthe cis isomer has two inter convertible
chair conformations, similar to cis-l,2-dimethylcyclo-hexane. Also, just as in the
case of the latter, the "flipping" or chair inversion converts the molecule to its mirror
image. cis-Decalin is therefore a non-resolvable dl pair, cis- Decalin also has a
twofold axis of symmetry, passing through the C9C10 bond at right angles to the
bond in a plane bisecting the dihedral angle between the 9- and 10-hydrogens. Thus
the symmetry number is thus also 2.
Since both cis- and trans-decalin have a symmetry number of 2, their
difference in entropy should result only from the fact that the cis isomer is a 'dl' pair
(even though non-resolvable) and should favor the cis isomer by R In 2 or 1.38
cal./deg. mole.

The experimental value is 0.55 cal/deg. mole, i.e., less than the

theoretical, suggesting that at least in the liquid phase there is slightly more ordering
of the molecules of the cis isomer than of the trans.

18

Fig: cis Decalin and Trans- ecalin

From the enthalpy and entropy differences between cis- and- trans their freeenergy difference at 250C may be calculated to amount to about 2.4 kcal./mole.
This is in semi quantitative agreement with the observation that the
equilibrium between cis- and trans-1 -decalone favors the trans isomer by between
10:1 and

20: l.

That trans-decalin is a rigid molecule whereas the cis isomer has two inter
convertible conformations is dramatically demonstrated by the nuclear magnetic
resonance spectra of these compounds.
cis- Decalin shows a single narrow resonance line, since, because of the rapid
flipping of the molecule from one chair form into the other, all methylene hydrogens
become identical and are seen in an average position as far as the NMR spectrum is
concerned. trans'-Decalin, on the other hand, shows a broad and partially resolved

19

base caused by the non-equivalent, equatorial and axial hydrogens and complicated
by the spin-spin coupling between them.
The difference in potential energy between the cis- and transs-9-methyldecalin system (which occurs in the A/B rings of the steroids) is considerably less
than that

20

Fig: The Triterpenes -Amyrin and Lupeol

between cis- and trans-decalin. The angular methyl group trans-9methyldecalin is axial and gives rise to four butane-gauche interactions (two with
respect to either ring of methylcyclohexane). In cis-9-methyldecalin, however, the
methyl group is axial with respect to one ring only and equatorial with respect to the
other, giving rise to two butane-gauche interactions in addition to the three already
present in the cis-decalin system. The total number of butane-gauche interactions in
the cis compound is therefore five, i.e., only one more than in the trans isomer, and

21

the difference in enthalpy should thus be 0.9 kcal./mole. With such a small H, in
entropy ( S) between the isomers may cause F to be either positive or negative.
Accordingly, in some 9-methyldecalin systems the cis isomer is found to be more
stable, thermodynamically, whereas in others the trans form predominates at
equilibrium
For the parent compound, 9-methyldecalin (liquid state), the trans isomer has
the lower enthalpy, Delta H being 0.55 0.28 kcal./mole from temperature
dependence of equilibrium or 1.39 0.64 kcal./mole from the difference in heats of
combustion.

Here, as in the case of the decalins, the entropy favors the cis isomer slightly,
although again by less than would be expected on the basis that the cis isomer is a
(non-resolvable) dl pair.

22

CONFORMATIONAL ANALYSIS OF SUGARS

Conformational analysis of monosaccharides:
1,2-Glycols form complexes in cuprammonium solutions, a five-membered
ring being produced in which the copper atom is linked to two oxygen atoms.
Furthermore, the extent of complex formation depends on the spatial arrangement
of the two adjacent hydroxyls, the most favored position being that in which the two
groups and the two carbon atoms to which they are attached lie in one plane.

In six-membered rings, the hydroxyl groups of 1,2-diols, if cis, are a,e and if
trans are e,e or a, a. Now, the projection angle between 1a,2e or le,2e substituents is
60o and that for 1a,2a is 180.

Reeves (1946) showed that complex formation occurred only if the projection
angle was 0 (the most favoured position mentioned above) or 60 . Since complex
formation changes the molecular rotation, the molecular rotational shift will indicate
the extent of complex formation.

Reeves (1950), using this cuprammonium complex formation, has shown that
the pyranose sugars assume a chair form in preference to any boat form wherever
both are structurally possible. Substitution of an oxygen atom for a carbon atom in

23

cyclohexane causes only minor distortions in the ring (Hassel et al., 1947), and
consequently the general conformational features are retained in the pyranose
sugars.

Reeves (1951) proposed the two regular conformations shown, and named
them Cl (the normal chair) and 1C (the reverse chair).

Reeves (1958) pointed out that there is an infinite number of skew

conformations in which angle strain is absent. It is still usual, however, to use the
regular conformations of Reeves since these are readily related to the Haworth
formulae.

There are various descriptions other than the C1 and 1C described above, example.
(a) The position of the anomeric hydroxyl or a substituent group (C-1 in aldoses and
C-2 in ketoses) in alpha-anomers is used as reference. Thus, with C = chair, A =

24

axial, and E = equatorial, CA and CE refer to the anomer in which the hydroxyl or a
substituent is respectively axial or Equatorial
(b) The conformation of the ring is indicated by C (chair), B (boat), and HC (halfchair). Numbers are then used, superscripts to indicate ring-atoms that lie above the
reference plane (which is defined by the plane containing atoms 2,3,5 and the ring
oxygen) and subscripts to indicate ring-atoms which lie below the reference plane.
Descriptions (a) and (b) may be illustrated with D- glucopyranose (Z = OH
or a substituent group): it might also be noted that there are six possible boat forms
(B1-B3 and 1B-3B), but since the chair forms are preferred.

25

Conformations of Monosaccharaides:
1) 1, 2- cis -Groups in the projection and perspective formulae are a, e or e, a in the
conformational representation.
2) 1, 2- cis -Groups in the projection and perspective formulae are e, e or a, a in the
conformational representation.
3) For D-aldohexoses in the normal chair form (C1), the -form has the anomeric
hydroxyl group in the axial position; in the reverse chair (1C) the -form has the
anomeric hydroxyl group in the equatorial position.
4) Epimerisation of a hydroxyl group involves the conversion of the axial position
into the equatorial or vice versa.
Various methods are used to study conformational analysis of the
monosaccharides. One method involves the estimation of the instability rating of
the various conformations.
This is done by the instability factors, which was introduced by Reeves
(1951) and later modified by Kelly (1957). The application of these rules has led to
predictions which are in good agreement with the experimental results.
1) The chair confirmation is usually preferred to the boat (or) twist boat
whenever both are structurally possible.

26

2) Axial hydroxyl groups ((or) any substituent other than hydrogen) increase the
instability of the molecule. Each axial hydroxyl group results in one instability
unit.
3) 1, 3 interactions involving axial hydroxyl result in 0.5 instability unit.
4) An axial CH2OH group (at C-5) results in two instability units if only axial
hydrogens are on C-l and C-3. If an axial substituent other than hydrogen is
on C-l or C-3, the instability factor is 2-5 units.
5) If the hydroxyl group (i.e.. an oxygen atom) on C-Z is axial and the oxygen
atom on C-l is equatorial, this results in 2.5 instability units. This situation is
referred to as the Delta-2 condition or Delta-2 instability factor. Its origin is
not fully understood, but it appears to be due to dipole interaction.
6) In addition to this method (instability rating), physical methods are used in
conformational analysis and also to identify and elucidate structures
monosaccharides.
X-Ray Analysis:
This is limited to studies on the solid compound, and consequently the results
may not apply to con formations when the compound is in solution.

27

The X-ray analysis of the p-bromo-phenylhydrazones of D-crabinose and Dglucose has shown that these are pyranose forms, whereas those of D-ribose and Dmannose are open-chain derivatives, as are also the P-Bromophenyl osazones of Dribose and D-glucose.
Infrared Spectroscopy:
By means of this technique, it is possible to identify monosaccharides and to
some extent, determine configuration, structure and confirmation.
Thus, for example, the identification of various groups is readily carried out,
and the and anomers may be differentiated.
The validity of the results obtained for the differentiation of the - and anomers has been questioned.

NMR Spectroscopy:
NMR spectroscopic studies of monosaccharides and their derivatives have
led to a number of generalizations which are used for the purpose of identification
and assignment of configuration and conformation. Deuterium oxide is a very useful
solvent (in these NMR studies) since it permits the examination of all CH protons.

28

On the other hand, dimethyl sulphoxide (preferably deuterated) as solvent

permits the examination of hydroxylic protons (in this case, no exchange reaction
can occur).
(i) Anomeric protons (CH) almost always occur at lower field than any other ringhydrogens (due to the deshielding effect of two oxygen atoms attached to C-l
Anomeric protons also show characteristic coupling constants with the proton on C2. For -glucopyranose derivatives, J 1,2 for eH1, is 3-3.6 Hz (this is also the case for
other sugars with eH1 and aH2); and for -manno- pyranose, J1,2 for eH1,eH2 is 1.0 1.5 (and is the case for other sugars with eH1, eH2).
(ii) Axial ring-hydrogens usually appear upheld with respect to equatorial
hydrogens.
(iii) Axial hydroxylic protons (in pyranoses) usually appear up field (0-3 p.p.m.)
with respect to equatorial hydroxylic protons. This is also the case for the anomeric
hydroxylic protons. Long-range coupling is observed al 100 MHz between hydroxyl
groups and axial vicinal ring-hydrogens.
For example, a-glucopyranose shows a signal that is a quartet: C1OH and
C2H splitting, J 4.5 Hz; C1- OH and C2- H splitting, J 0.7 Hz. The -anomer. On
the other hand, shows a doublet: C1OH and C2H splitting, J 6.4 Hz

29

(iv) Vicinal trans diaxial protons in pyranose rings have large coupling constants (512 Hz). Vicinal e,e (trams) and e,a (cis) protons cannot be differentiated; J for both
of these is 1-3-6 Hz. Generally, J for axial and equatorial protons attached to the
same carton atom is about 2 Hz.
Also, because the CH2OH group (on C-5 of the ring) is almost always
equatorial, this fixes the proton on C-5 an axial. With this as a 'standard', it may be
possible to deduce the positions (a or e) of the other ring protons.
(v) For acetylated pyranosides, the methyl group on an axial secondary hydroxyl
group occurs downfield with respect to that on an equatorial secondary hydroxyl
group. Thus, axial, 7.80-7.90; equatorial, 7.88-8.03; these relative positions of the
signals also hold for the acetamide group. Thus axial, 7.92-8.04; equatorial, 8.038.12
(vi) For methylated pyranosides, the methyl group on an axial hydroxyl group occur
with respect that on an equatorial hydroxyl group. Thus: : axial, 6.54-6.64;
equatorial, 6.64-6.67. Many exceptions, however, are known.
An equatorial CMe group has a 8.76-8.84. These generalizations are
useful, but may lead to wrong conclusions in rings which have been deformed by,
e.g., steric effects.
30

The use of these relationships may be illustrated by the elucidation of the

configuration conformation of desosamine, a 3-aminohexose that has been isolated
from a series of anti biotics.
A freshly prepared solution of this compound showed the presence of an axial
anomeric proton. Hence crystalline desosamine is the anomer. (Woo et al., 1962).
Also, the values of the coupling constants J2,3, J4, 5 were all between 10 and 12 Hz,
and consequently there are axial protons on C-2, C-3, (C-4) and C-4.

Fig: Desosamine

31

Mass Spectroscopy:
This is now sufficiently developed to be used as a means of determining, e.g.,
the size of a ring of a monosaccharide (pyranose of furanose), the number and
position of methyl ether and acetyl groups in a methylated sugar, position of linking
in a disaccharide, etc. the mass spectrum of B-D-glucopyranose penta-acetate has
been examined in great detail, and this spectrum contains features common to most
aldopyranoses.
The molecular ion (M = 390) is absent; this is due to the ready elimination of
the glycosidic acetyl group as a free radical (CH3CO ;m/e 43) Hence the highest
mass recorded is m/e 347 (390 - 43), and is a very weak peak. three ions are always
observed (and also in all fully acetylated sugars) provided acetoxy groups or 1,2 or
1,3-positions. These ions are the acetylium ion (m/e 43), the diacetyl oxonium ion
(m/e 103) and the tracetyl oxonium ion (m/e 145).

32

Another common feature is the elimination of acetic acid followed by the

elimination of keten. This results in the overall loss of 102 units to give a very strong
peak at m/e M 102 (i.e., 288 in our example. The fragmentation paths proposed
are:

The spectrum is complicated; strong peaks include m/e 43, 73, 98, 103, 115,
140, 145, 157, 200,242,288; and weak peaks m/e 330, 331, 347 (masses in italics
have been accounted for in the above discussion). The peaks given are believed to
be produced by paths (i) and (ii).

33

34

Now let us consider fully methylated glycosides, e.g., methyl 2,3,4,6-tetra-Omethyl-alpha-D-gluco- pyranoside. The fragmentation paths of this compound show
some similarities to those of the penta acetates:
(i) No molecular ion (M= 250) is observed because of the ready elimination of the
glycosidic methoxy-group as a free radical (CH3O; m/e 31). Hence the highest mass
recorded is m/e 219 (250 31), and is a very weak peak.

35

(ii) Methanol is now eliminated (the methoxy group at position 3 is lost

preferentially)
(iii) Ethylene oxide is eliminated finally.
Strong peaks include m/e 75, 88, 101,187, and weak peaks m/e 71, 73, 111, 155,
173,205, 219 is not certain how all of these are produced.

36

The other ions are:

Acetates of partially methylated sugars (pyranosides) behave like fully

acetylated sugars one or two methyl ether groups are present, or like the fully
methylated sugars if four methyl ether groups are present. Acetates and methyl ethers
of aldofuranosides show fragmentation patterns which differ from those of the
corresponding aldopyranosides, and this is due to the presence of the furan ring. it is
because of these differences that the pyranose and furanose isomers can be
distinguished.
Optical rotations and ORD curves.
A difficulty in studying carbohydrates by ORD is the lack of suitable
chromophore that most simple sugars give plain dispersion curves. However, the
curves D- and L-sugars are similar in shape but have opposite signs. On the other
37

hand, if the sugar molecule contains a carboxyl or an acyl group, then a Cotton effect
is observed. This has been gamma-lactones and it has been shown that when the
hydroxyl on the carbon atom adjacent to the carbonyl group (of the lactone) has the
S-configuration, the ORD curve (at about 220-230 nm) is positive; and vice versa,
i.e., the R-configuration leads to a negative curve.
Examples are:
a) D- arabino lactone (c-2, s: positive)
b) D- Glucano lactone (c-2, r: negative)

38

A particularly useful derivative of alcohols that shows the Cotton effect is the
xanthate; this has been applied to sugar acetates, e.g., (C) [Z = SCOOEt].
The ORD curves of the two anomers different and so may be distinguished.
Chromatography:
This is used for the separation, estimation and identification of monosaccharides.
Chemical Methods:
D- Glucopyranose is an equilibrium mixture (in solution) of the and - anomers.
Then conformations of these are:

39

These conformations are of the C1 type and, the C1 confirmation for D-sugars
is usally more stable than the 1C. The corresponding 1C conformations of and
D Glucopyranose are as shown by changing into the other forms, with all
equatorial groups now axial, and vice versa.

It was pointed out that the configuration at C-l, as well as all the other asymmetric
carbon atoms, in the L-form. Thus, in the -anomer of an L-sugar, the C1 hydroxyl
group is equatorial and in the -anomer it is axial, e.g., the conformations of - and
-L-glucopyranose are:

40

These would be expected to be less stable than the corresponding 1C forms.

It might also be noted that the L-sugar may be drawn as the mirror image of the Dsugar, but now the mirror image of a Cl-D-sugar is the lC-L-sugar.
Shaw et al. (1965) have studied aqueous solutions of some monosaccharaides by
means of NMR spectroscopy and were able to estimate the amount of -and pyranose forms present.

41

Sugars

(%)

(%)

D- Glucose

36

64

D- Glactose

35

65

D-Mannose

64

36

D-Xylose

29

71

L Arabinose

63

37

D- Lyxose

69

31

D- Ribose

18

54

The authors also showed that the following were in conformational

equilibrium in According to Lemieux et al. (1965), -D-ribopyranose is in the C1
conformation and the alpha anomer is not in a chair conformation. On the other hand,
Bhacca et al. (1967) have shown from NMR studies that tetra-0-acetyl- Beta-Dribopyranose is, at room temperature, in continuous motion between the two chair
conformations.

42

C1

C1+ 1C

1C

and D Glucose

D Lyxose

D Ribose

and D Galactose

D Ribose

and Arabinose

and D Mannose
and D Xylose
and D Lyxose

Angyal et al. (1971) have shown that sugars containing an a-e-a sequence of
three hydroxyle groups in a pyranose ring, or a cis-cis sequence in a furanose ring,
form complexes with metal ions in aqueous solution. This is particularly the case
with the alkaline-earth metals. -D-Allopyranose has the required arrangement of
the hydroxyl groups but the Beta-anomer has not. These workers found that addition
of calcium chloride increased the content of the -anomer. Thus, it is possible to
shift the position of equilibrium of - and Beta-anomers.
Investigation of the ring-size of sugars from the point of view of
conformational analysis resulted in some interesting conclusions. Let us consider the
furanose (I) and pyranose (II) D( + )-glucose (R = CHOHCH2OH) in solution. In (I)
(envelope conformation; the 2- and 3-hydroxyl groups are axial, but in (II) all the
large groups, OH and CH2OH, are equitorial Hence it can be anticipated that the
43

furanose form will be less stable than the pyranose (chair) form and so the
equilibrium will lie far to the right. Ferrier (1963) has examined crystalline -DGlucose by means of x-ray analysis and had shown that the molecule has the
pyranose ring in the chair form with all the substituents in the equatorial positions.

Glucose, mannose, xylose and lyxose show normal mutarotation, and this is
readily explained in terms of the equilibrium described, i.e., that there are essentially
two forms present, - and - pyranose. Also it has been shown for these four sugars
that the amount present as the -anomer is: Glucose, 64; mannose, 36; xylose, 71;
lyxose, 31 per cent. This may be explained as follows. In the - anomers of D-xylose
and D-glucose, (III), which are configurationally related, the 1-OH group is axial.

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Whereas in the corresponding Beta-anomers, (IV), it is equatorial.

Consequently, the Beta-anomers will be more stable than the alpha- (the latter

45

contains one instability unit). In fact, since Beta-D-glucopyranose is the only

hexopyranose which has no instability units, it would be expected to be the most
stable D-aldohexose;
It might be noted here that sugars which have the same configurations in the
ring form are said to be homonorphous. In D-lyxose and D-mannose, which are also
configurationaliy related (i.e., are homomorphous), the 2-OH group is axial in both
Alpha-(V) and Beta- anomers (VI), but since the Beta-anomer (VI) is in the Delta2-condition, this form is less stable than the alpha-anomer (V) (by two instability
units), and so the latter predominates.
Ribose, arabinose, galactose and talose differ from the sugars described above
in that they show abnormal mutarotation curves. This requires the presence of three
or more different components in appreciable amounts at equilibrium. Let us consider
arabinose and galactose.
Inspection of formulae (IV) and (XIII) shows that the furanose forms of L( +
)-arabinose and D(+) - Galactose are configurationally related (i.e., are
homomorphous). Thus, we may write these sugars as (VII) and (VIII), and it can be
seen that in (VIII) all the large groups at 2, 3 and 4 are equatorial, Whereas in (VIII)
the 4-OH group is axial.

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Hence (VII) will be much more stable than (I), and so (VII) can be expected
to make some contribution to the equilibrium (VII) , (VIII). In the view of what has
been said above, it might have been anticipated that -lactones would be more stable
than

-lactones but, as we have seen, the reverse is true in practice.

The reason for this is not certain, but one explanation offered involves the

electrostatic repulsions that can operate between the C-O bond of the carbonyl group
and a P-orbital of a lone pair of electrons on the ring oxygen.

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In (IX) the C=O is almost eclipsed with with the 2-e, -H, and is straggered
with the P-Orbital on the ring-oxygen atom, whereas, in (X) the latter interaction
will be from the eclipsed conformation.

The electrostatic forces can play a very important part in stabilities of

confirmations and so, if we assume that these electrostatic repulsions are
considerable in (X), then (IX) will be the more stable lactone. This argument has
been applied to un- substituted lactones, but when we consider the lactones of the
methylated sugars.

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