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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.


(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 5 .In the presence of a base and the failure of the unsaturated analog of camphoric acid to form an anhydride.

Bicycloctane-2. and camphenonic and Ketophonic acids.6-dione does not show the acidic properties of a 1.3-diketone (the anion is incapable of resonance). do not readily decarboxylated. although they are β.Keto acids. 6 . The limitations of the Bredt rule have been elegantly demonstrated by Prelog and coworkers. because they cannot achieved the required enolic transition state.

Fig: Further Examples of Bredt Rule 7 .Ring closure of the diketone may give rise to either the fused-ring system 'A' or the bridged-ring system 'B'. the bridged system B is formed along with A. only 'B' results. when n =5. only the fused system 'A' is formed. When n= 4. and when n = 6.

Whereas camphenonic acid and its isomer. as well as similar β – keto acid containing the [2 8 . 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.2. keto-pinic acid which contain the [2. 3.The Bredt rule no longer applies to the [5. 1] system.keto acids seem to somewhat less severe.1] system. A N= 4 65% N=5 32% N=6 NONE (OR) B N= 4 NONE N=5 14% N=6 76% Fig: Limitations of Bredt’s Rule The stereo chemical restrictions in decarboxylation’s of β.

3. But in ‘B’ it is in one carbon – bridge.2] system. 9 .diketo – bycyclo [3. 2. It might be noted that the bridged benzene derivatives also do not follow Bredt’s rule.dimethyl ester can be decarboxylated by heating. Some further reactions of the Norbornane System: The Norbornane (bicyclo [2..5.6.7 tetra carboxylic acid.2 .2. The difference may well lie in the fact that in ‘A’ the carbonyl group is in the three carbon bridge.3.1] nonane -1.1] 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.3. especially since the system is involved in some of the Wagher.Meerwein rearrangements which make terpine chemistry so intriguing. cannot be decarboxylated by heating in quinoline to 2400.7. although the next higher homolog (n=4) is decarboxylated under these conditions. A similar acid (n=3) on the other hand. fail to decarboxylate.Alder reaction starting with cyclo pentadiene. Some further reactions of this system will be considered in this reaction.

10 .Fig: Limitations of Bredt Rule. Model considerations indicate that. is an appreciably strained system. 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. Further examples Norbornane despite its easy accessibility.

as evidenced by its heat of hydrogenation which averages 34 K Cal/ Mole per double bond. its ready reaction to Norbornane by means of lithium and ethyl amine.2. Its ready reaction with phenyl azide to give a dihydrotriazole. 2. it rearranges the tropylidene. and its ability to act as a dienophile in the Diels – Alder reaction.Comparison of the heats of combustion of the 2-Ketones derived from Norbornane and its next higher homolog. 11 . Its tendency to undergo a reverse Diels – Alder reaction upon heating. Norbornadiene is also quite strained.2] octane-2. 2] octane. bicyclo [2. Norbornylene is even more strained as evidence by its high heat of hydrogenation ca.2. 2] octane suggests that the extra angle strain in the Norbornane system amounts to about 6. 2. 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. The driving force in this process may be both loss of strain and gain of resonance energy.3 K Cal/ Mole. Upon heating. Fig: Bicyclo [2. It shows an evidence for an un usually reactive double bond.1] heptanone-2 and Bicyclo[2.

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. Although the Diels. 12 . more sterically crowded than the exo form. in many cases. This isomer is.Alder synthesis of two substituted Norbornane usually produces the endo isomer by kinetic control. 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.Similar evidence for the strained nature of Norbornane system comes from the rearrangement of the hydrogenated cyclopentadine dimer to adamentane.

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. this system is generally approached by reagents from the endoside side. 13 Thus . catalytic hydrogenation of camphor gives largely (over 90%). 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.Fig: Norbornadiene.

14 .Fig: Approach on reagents on exo side of Norbornane system Isoborneol which has the exo configuration (i. the hydrogen approaches from the endo side)..e. Reduction with lithium aluminum hydride (steric-approachcontrolled) similarly gives mostly isoborneol (90%) with but a little borneol (10%).

kinetic work has shown that the rate of rearrangement is in sensitive to added chloride ions. The rearrangement has been depicted as proceeding through a Fig: α – pyrine –hydrochloride – bornyl chloride rearrangement succession of classical carbonium ions. Concerted with detachment of the bridge.pyrine is treated in ether solution with gaseous hydrogen chloride at —15°c. there is an inversion at the migration origin (the chlorine attacks itself from the rear whereas the bridge was in front). rearranges to bornyl chloride. it would be attractive to postulate an attack of chloride at the bridgehead. However. upon warming.When α . but this picture cannot be correct. an unstable addition product is formed which. since the bornyl carbonium ion should give rise to a mixture of isoboryl and bornyl chloride. From the stereochemical point of view. and therefore the concerted mechanism is untenable which 15 .

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.indicates that the rearrangement proceeds via a non-classical (or) mesomeric carbonium ion intermediate between A & B. 16 . Upon standing the hydrochloride rearranges to isobornyl chloride. this rearrangement also involves inversion at the migration origin.

of which the trans is the more stable. which first convinced chemists that cyclohexane rings in decalin and elsewhere are puckered. 2. in good agreement with the calculated value. and not planar. The counting of butane-gauche interactions in the decalins reveals three such interactions in the cis isomers and none in the trans./mole.Therefore the calculated difference in heats of formation between the decalins is 3 x 0.CONFORMATION ANALYSIS OF DECALINES (OR) CONFIRMATIONS OF DECALINES The most important compound is the 6-6 compound decalin. Trans Decalin has a center of symmetry (midway between C9 and C10) and is therefore an optically inactive molecule. as postulated by Baeyer./mole for the vapor./mole for the liquid phase or 3. It also has a two fold axis of symmetry 17 . It was probably the demonstration by W. 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.9.7 kcal. or 2.7 kcal. as postulated by Sachse and Mohr .1 kcal. The trans isomer being the more stable.Huckel that decalin may exist in cis and trans forms.

C9 and C10. i.decalin./deg. The experimental value is 0..55 cal/deg. thus its symmetry number is 2.(passing horizontally between C2 and C3.a bonds—the cis isomer has two inter convertible chair conformations.2-dimethylcyclo-hexane. not through a. cis. C7 and C6). passing through the C9—C10 bond at right angles to the bond in a plane bisecting the dihedral angle between the 9.e. similar to cis-l. less than the theoretical.and trans-decalin have a symmetry number of 2. cis -Decalin is dissymmetric . the "flipping" or chair inversion converts the molecule to its mirror image.and 10-hydrogens.which is rigid because the ring fusion can only be through e.38 cal. unlike trans . However. Since both cis.e. mole. mole. 18 . just as in the case of the latter. Thus the symmetry number is thus also 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.Decalin also has a twofold axis of symmetry. cis-Decalin is therefore a non-resolvable dl pair. Also. suggesting that at least in the liquid phase there is slightly more ordering of the molecules of the cis isomer than of the trans.

all methylene hydrogens become identical and are seen in an average position as far as the NMR spectrum is concerned. shows a broad and partially resolved 19 .4 kcal.and trans-1 -decalone favors the trans isomer by between 10:1 and 20: l.trans their freeenergy difference at 250°C may be calculated to amount to about 2.Fig: cis – Decalin and Trans.Decalin shows a single narrow resonance line. since. because of the rapid flipping of the molecule from one chair form into the other.and. trans'-Decalin. on the other hand. 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./mole.ecalin From the enthalpy and entropy differences between cis. cis. This is in semi quantitative agreement with the observation that the equilibrium between cis.

and transs-9-methyldecalin system (which occurs in the A/B rings of the steroids) is considerably less than that 20 . equatorial and axial hydrogen’s and complicated by the spin-spin coupling between them. The difference in potential energy between the cis.base caused by the non-equivalent.

The total number of butane-gauche interactions in the cis compound is therefore five. however. and 21 .and trans-decalin. i.Fig: The Triterpenes β-Amyrin and Lupeol between cis. giving rise to two butane-gauche interactions in addition to the three already present in the cis-decalin system. In cis-9-methyldecalin. the methyl group is axial with respect to one ring only and equatorial with respect to the other.. only one more than in the trans isomer. The angular methyl group trans-9methyldecalin is axial and gives rise to four butane-gauche interactions (two with respect to either ring of methylcyclohexane).e.

55 ± 0.9 kcal. in some 9-methyldecalin systems the cis isomer is found to be more stable. With such a small ∆ H. Accordingly.64 kcal. whereas in others the trans form predominates at equilibrium For the parent compound. the trans isomer has the lower enthalpy. 22 ./mole from the difference in heats of combustion./mole from temperature dependence of equilibrium or 1. Here./mole.28 kcal. the entropy favors the cis isomer slightly.39 ± 0. although again by less than would be expected on the basis that the cis isomer is a (non-resolvable) dl pair. as in the case of the decalins. in entropy (∆ S) between the isomers may cause ∆ F to be either positive or negative. thermodynamically.the difference in enthalpy should thus be 0. 9-methyldecalin (liquid state). Delta H being 0.

2e or le. Now. using this cuprammonium complex formation. the projection angle between 1a.e or a.2a is 180.2e substituents is 60o and that for 1a.2-Glycols form complexes in cuprammonium solutions. Since complex formation changes the molecular rotation. the molecular rotational shift will indicate the extent of complex formation. Substitution of an oxygen atom for a carbon atom in 23 . In six-membered rings. are a. the hydroxyl groups of 1.e and if trans are e. if cis. a.2-diols. the extent of complex formation depends on the spatial arrangement of the two adjacent hydroxyls. Furthermore. 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. Reeves (1950). has shown that the pyranose sugars assume a chair form in preference to any boat form wherever both are structurally possible. a five-membered ring being produced in which the copper atom is linked to two oxygen atoms.CONFORMATIONAL ANALYSIS OF SUGARS Conformational analysis of monosaccharide’s: 1. Reeves (1946) showed that complex formation occurred only if the projection angle was 0 (the most favoured position mentioned above) or 60 .

with C = chair. however. example. There are various descriptions other than the C1 and 1C described above. Thus. (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. A = 24 .. It is still usual.cyclohexane causes only minor distortions in the ring (Hassel et al. and named them Cl (the normal chair) and 1C (the reverse chair). to use the regular conformations of Reeves since these are readily related to the Haworth formulae. Reeves (1958) pointed out that there is an infinite number of skew conformations in which angle strain is absent. and consequently the general conformational features are retained in the pyranose sugars. Reeves (1951) proposed the two regular conformations shown. 1947).

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).3.axial. Descriptions (a) and (b) may be illustrated with D. and E = equatorial. Numbers are then used. and HC (halfchair).5 and the ring – oxygen) and subscripts to indicate ring-atoms which lie below the reference plane. 25 .glucopyranose (Z = OH or a substituent group): it might also be noted that there are six possible boat forms (B1-B3 and 1B-3B). superscripts to indicate ring-atoms that lie above the reference plane (which is defined by the plane containing atoms 2. B (boat). but since the chair forms are preferred.

2) 1. the α-form has the anomeric hydroxyl group in the axial position. a in the conformational representation. 26 . e or e. One method involves the estimation of the instability rating of the various conformations. 4) Epimerisation of a hydroxyl group involves the conversion of the axial position into the equatorial or vice versa. a in the conformational representation. 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. in the reverse chair (1C) the α-form has the anomeric hydroxyl group in the equatorial position.cis -Groups in the projection and perspective formulae are e. 3) For D-aldohexoses in the normal chair form (C1).Conformations of Monosaccharaides: 1) 1. This is done by the instability factors. e or a. which was introduced by Reeves (1951) and later modified by Kelly (1957). 2.cis -Groups in the projection and perspective formulae are a. 2. Various methods are used to study conformational analysis of the monosaccharide’s.

27 . 3 interactions involving axial hydroxyl result in 0. and consequently the results may not apply to con formations when the compound is in solution. 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 monosaccharide’s. the instability factor is 2-5 units. If an axial substituent other than hydrogen is on C-l or C-3. this results in 2. Each axial hydroxyl group results in one instability unit.5 instability units.5 instability unit. 5) If the hydroxyl group (i.e. Its origin is not fully understood.. This situation is referred to as the Delta-2 condition or Delta-2 instability factor. an oxygen atom) on C-Z is axial and the oxygen atom on C-l is equatorial.2) Axial hydroxyl groups ((or) any substituent other than hydrogen) increase the instability of the molecule. X-Ray Analysis: This is limited to studies on the solid compound. 4) An axial CH2OH group (at C-5) results in two instability units if only axial hydrogen’s are on C-l and C-3. 3) 1.

for example. Thus.and βanomers has been questioned. Infrared Spectroscopy: By means of this technique. and the α and β – anomers may be differentiated. NMR Spectroscopy: NMR spectroscopic studies of monosaccharide’s and their derivatives have led to a number of generalizations which are used for the purpose of identification and assignment of configuration and conformation. structure and confirmation. it is possible to identify monosaccharide’s and to some extent. the identification of various groups is readily carried out. as are also the P-Bromophenyl osazones of Dribose and D-glucose. determine configuration. whereas those of D-ribose and Dmannose are open-chain derivatives. Deuterium oxide is a very useful solvent (in these NMR studies) since it permits the examination of all C—H protons.The X-ray analysis of the p-bromo-phenylhydrazones of D-crabinose and Dglucose has shown that these are pyranose forms. 28 . The validity of the results obtained for the differentiation of the α.

H splitting.2 for eH1.p.0 1. This is also the case for the anomeric hydroxylic protons. The β-anomer.2 for eH1. J 6. eH2).6 Hz (this is also the case for other sugars with eH1 and aH2). is 3-3. On the other hand.OH and C2. shows a doublet: C1—OH and C2—H splitting.5 (and is the case for other sugars with eH1. (iii) Axial hydroxylic protons (in pyranoses) usually appear up field (0-3 p. For example. J1. Long-range coupling is observed al 100 MHz between hydroxyl groups and axial vicinal ring-hydrogens.) with respect to equatorial hydroxylic protons. J 0. (i) Anomeric protons (C—H) almost always occur at lower field than any other ringhydrogen’s (due to the deshielding effect of two oxygen atoms attached to C-l Anomeric protons also show characteristic coupling constants with the proton on C2.5 Hz. no exchange reaction can occur).7 Hz.On the other hand. and for α-manno. For α-glucopyranose derivatives. a-glucopyranose shows a signal that is a quartet: C1—OH and C2—H splitting.pyranose. J 1.m.4 Hz 29 . J 4. C1.eH2 is 1. (ii) Axial ring-hydrogen’s usually appear upheld with respect to equatorial hydrogen’s. dimethyl sulphoxide (preferably deuterated) as solvent permits the examination of hydroxylic protons (in this case.

038. equatorial. steric effects. this fixes the proton on C-5 an axial. equatorial. Thus.76-8. 6.80-7.90.92-8.12 (vi) For methylated pyranosides. 8.67.a (cis) protons cannot be differentiated.03. 30 .84. J for axial and equatorial protons attached to the same carton atom is about 2 Hz. Vicinal e. these relative positions of the signals also hold for the acetamide group. are known.. 7. however. 6. J for both of these is 1-3-6 Hz. Also.e (trams) and e. With this as a 'standard'. because the CH2OH group (on C-5 of the ring) is almost always equatorial. An equatorial C—Me group has a τ 8. Thus: τ: axial. 7.04. the methyl group on an axial hydroxyl group occur with respect that on an equatorial hydroxyl group. τ axial. the methyl group on an axial secondary hydroxyl group occurs downfield with respect to that on an equatorial secondary hydroxyl group. Generally. (v) For acetylated pyranosides. 7.54-6.g. e.64-6. Thus τ axial.64.88-8. These generalizations are useful. it may be possible to deduce the positions (a or e) of the other ring protons. equatorial. Many exceptions. but may lead to wrong conclusions in rings which have been deformed by.(iv) Vicinal trans diaxial protons in pyranose rings have large coupling constants (512 Hz).

the values of the coupling constants J2.. (Woo et al.3. and consequently there are axial protons on C-2. A freshly prepared solution of this compound showed the presence of an axial anomeric proton. (C-4) and C-4. Also.The use of these relationships may be illustrated by the elucidation of the configuration conformation of desosamine. J4. a 3-aminohexose that has been isolated from a series of anti biotics. Fig: Desosamine 31 . Hence crystalline desosamine is the β anomer. C-3. 5 were all between 10 and 12 Hz. 1962).

3-positions. three ions are always observed (and also in all fully acetylated sugars) provided acetoxy groups or 1.g.Mass Spectroscopy: This is now sufficiently developed to be used as a means of determining. the size of a ring of a monosaccharide (pyranose of furanose)..2 or 1. The molecular ion (M = 390) is absent. the diacetyl oxonium ion (m/e 103) and the tracetyl oxonium ion (m/e 145). the number and position of methyl ether and acetyl groups in a methylated sugar. and this spectrum contains features common to most aldopyranoses. These ions are the acetylium ion (m/e 43). this is due to the ready elimination of the glycosidic acetyl group as a free radical (CH3CO . e. etc. 32 . the mass spectrum of B-D-glucopyranose penta-acetate has been examined in great detail.m/e 43) Hence the highest mass recorded is m/e 347 (390 .43). and is a very weak peak. position of linking in a disaccharide.

347 (masses in italics have been accounted for in the above discussion). 145.242. 157. strong peaks include m/e 43. 115. 140. 73. The fragmentation paths proposed are: The spectrum is complicated. and weak peaks m/e 330. 331. The peaks given are believed to be produced by paths (i) and (ii). This results in the overall loss of 102 units to give a very strong peak at m/e M — 102 (i. 33 . 200. 288 in our example..288.e.Another common feature is the elimination of acetic acid followed by the elimination of keten. 98. 103.

34 .

m/e 31). 35 .4. methyl 2.g.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.3. and is a very weak peak. e.. Hence the highest mass recorded is m/e 219 (250 — 31).Now let us consider fully methylated glycosides.6-tetra-Omethyl-alpha-D-gluco.

Strong peaks include m/e 75. 73. 219 is not certain how all of these are produced.187. 173.(ii) Methanol is now eliminated (the methoxy group at position 3 is lost preferentially) (iii) Ethylene oxide is eliminated finally. and weak peaks m/e 71. 101.205. 111. 36 . 155. 88.

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

the R-configuration leads to a negative curve. and vice versa.hand.. Examples are: a) D.arabino – γ – lactone (c-2. i.e.Glucano – γ – lactone (c-2. the ORD curve (at about 220-230 nm) is positive. then a Cotton effect is observed. if the sugar molecule contains a carboxyl or an acyl group. r: negative) 38 . s: positive) b) D. 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.

(C) [Z = —S—CO—OEt]. e. Chemical Methods: D..anomers.Glucopyranose is an equilibrium mixture (in solution) of the α – and β. The ORD curves of the two anomers different and so may be distinguished. Then conformations of these are: 39 .A particularly useful derivative of alcohols that shows the Cotton effect is the xanthate. this has been applied to sugar acetates. estimation and identification of monosaccharide’s.g. Chromatography: This is used for the separation.

in the L-form. and vice versa. the conformations of α.g. The corresponding 1C conformations of α – and β – D – Glucopyranose are as shown by changing into the other forms..and β -L-glucopyranose are: 40 . with all equatorial groups now axial. as well as all the other asymmetric carbon atoms. the C1 confirmation for D-sugars is usally more stable than the 1C. the C1 hydroxyl group is equatorial and in the α-anomer it is axial.These conformations are of the C1 type and. in the α-anomer of an L-sugar. Thus. e. It was pointed out that the configuration at C-l.

It might also be noted that the L-sugar may be drawn as the mirror image of the Dsugar. 41 . (1965) have studied aqueous solutions of some monosaccharaides by means of NMR spectroscopy and were able to estimate the amount of α-and αpyranose forms present. but now the mirror image of a Cl-D-sugar is the lC-L-sugar.These would be expected to be less stable than the corresponding 1C forms. Shaw et al.

-D-ribopyranose is in the C1 conformation and the alpha anomer is not in a chair conformation. at room temperature. (1967) have shown from NMR studies that tetra-0-acetyl.Lyxose 69 31 D.Glucose 36 64 D. On the other hand. 42 .Beta-Dribopyranose is. (1965).Glactose 35 65 D-Mannose 64 36 D-Xylose 29 71 L – Arabinose 63 37 D.Ribose 18 54 The authors also showed that the following were in conformational equilibrium in According to Lemieux et al.Sugars α(%) β(%) D. in continuous motion between the two chair conformations. Bhacca et al.

are equitorial Hence it can be anticipated that the 43 .C1 C1+ 1C 1C α – and β – D – Glucose α – D – Lyxose α – D – Ribose α – and β – D – Galactose β – D – Ribose α – and β – Arabinose α – and β – D – Mannose α – and β – D – Xylose α – and β – D – Lyxose Angyal et al. In (I) (envelope conformation. These workers found that addition of calcium chloride increased the content of the α-anomer. OH and CH2OH. Thus. or a cis-cis sequence in a furanose ring. (1971) have shown that sugars containing an a-e-a sequence of three hydroxyle groups in a pyranose ring. it is possible to shift the position of equilibrium of α.and Beta-anomers. Let us consider the furanose (I) and pyranose (II) D( + )-glucose (R = CHOHCH2OH) in solution. α-D-Allopyranose has the required arrangement of the hydroxyl groups but the Beta-anomer has not. the 2. but in (II) all the large groups. This is particularly the case with the alkaline-earth metals. Investigation of the ring-size of sugars from the point of view of conformational analysis resulted in some interesting conclusions. form complexes with metal ions in aqueous solution.and 3-hydroxyl groups are axial.

which are configurationally related. mannose. i. 64. α. Also it has been shown for these four sugars that the amount present as the β-anomer is: Glucose. xylose and lyxose show normal mutarotation. This may be explained as follows. Glucose. xylose. 71. 36.and β.e. (III).anomers of D-xylose and D-glucose. that there are essentially two forms present.furanose form will be less stable than the pyranose (chair) form and so the equilibrium will lie far to the right. the 1-OH group is axial. Ferrier (1963) has examined crystalline β-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.. and this is readily explained in terms of the equilibrium described. 44 .pyranose. lyxose. 31 per cent. mannose. In the α.

it is equatorial. (IV). Consequently. the Beta-anomers will be more stable than the alpha.(the latter 45 .Whereas in the corresponding Beta-anomers.

arabinose.e.Galactose are configurationally related (i. In D-lyxose and D-mannose. are homomorphous). and so the latter predominates. this form is less stable than the alpha-anomer (V) (by two instability units). are homomorphous).e. 3 and 4 are equatorial. since Beta-D-glucopyranose is the only hexopyranose which has no instability units.anomers (VI). This requires the presence of three or more different components in appreciable amounts at equilibrium. In fact. It might be noted here that sugars which have the same configurations in the ring form are said to be homonorphous. the 2-OH group is axial in both Alpha-(V) and Beta.. and it can be seen that in (VIII) all the large groups at 2.contains one instability unit). we may write these sugars as (VII) and (VIII). galactose and talose differ from the sugars described above in that they show abnormal mutarotation curves. Let us consider arabinose and galactose. it would be expected to be the most stable D-aldohexose. but since the Beta-anomer (VI) is in the Delta2-condition. Thus.. 46 . Ribose. which are also configurationaliy related (i. Whereas in (VIII) the 4-OH group is axial. Inspection of formulae (IV) and (XIII) shows that the furanose forms of L( + )-arabinose and D(+) .

Hence (VII) will be much more stable than (I). (VIII). 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. 47 . the reverse is true in practice. as we have seen. The reason for this is not certain. and so (VII) can be expected to make some contribution to the equilibrium (VII) . In the view of what has been said above. it might have been anticipated that δ-lactones would be more stable than γ-lactones but.

The electrostatic forces can play a very important part in stabilities of confirmations and so. This argument has been applied to un.In (IX) the C=O is almost eclipsed with with the 2-e.substituted lactones. in (X) the latter interaction will be from the eclipsed conformation. then (IX) will be the more stable lactone. whereas. -H. but when we consider the lactones of the methylated sugars. if we assume that these electrostatic repulsions are considerable in (X). 48 . and is straggered with the P-Orbital on the ring-oxygen atom.