Projections Fischer

Fischer projections provide a fnrther approach to the two-dimensional representations of three-dimensional formulae. They become particularly useful for molecules that contain several chiral centres, and are most frequently encountered in discussions of sugars (see 

Section 12.2). To start, though, let us consider just one chiral centre, and choose the amino acid we met earlier (see Section 3.4.2), (—)-(5)-serine. 

Fischer projection is equivalent to viewing molecule from the top 

However, when we come to manipulate Fischer projec- 

Manipulations we can do to a Fischer projection may at first glance appear confusing, but by reference to a model of a tetrahedral array, or even a sketch of the representation, they should soon become quite understandable, perhaps even obvious. The molecular manipulations shown are given to convince you of the reality of the following statements. 

A tetrahedral carbon atom is represented in a Fischer projection by two crossed lines. The horizontal lines represent bonds coming out of the page, and the vertical lines represent bonds going into the page  

Because a given chiral molecule can be drawn in many different ways, it s often necessary to compare two projections to see if they represent the same or different enantiomers. To test for identity, Fischer projections can be moved around on the paper, but care must be taken not to change the meaning of the projection inadvertently. Only two kinds of motions are allowed  

A 90° rotation, however, breaks the Fischer convention by exchangiii the groups that go into the plane and those that come out. In the 1 lowing Fischer projection of (i )-lactic acid, the -H and -OH grou come out of the plane before rotation but go into the plane after a rotation. As a result, the rotated projection represents (S)-lactic at  

A Fischer projection can have one group held steady while the othe three rotate in either a clockwise of a counterclockwise direction. Fq example  

These are the only kinds of motion allowed. Moving a Fischer proje tion in any other way inverts its meaning. 

The R and S system is useful in discussing the Fischer projection, which is one of the most important two-dimensional representations of chiral molecules. This type of drawing was initially developed to display the stereochemical relationships among carbohydrates with several chiral centers, but it is also useful in many other applications. In a Fischer projection, molecules are represented by crossing vertical and horizontal lines, with each intersection representing a carbon atom. Horizontal lines represent bonds that would project forward in space if we drew the molecule using perspective notation 

It cannot be that all of the atoms lie in the plane. If that were the case, the structure would not be chiral. 

Hoffman, P. H. Ong, E. C. Weigang, O. E., Jr. Nugent, M. J. /. Am. Chem. Soc. 1974,96,2620. The Fischer projection is also called the Fischer-Tollens projection (reference 11). Lichtenthaler, F. W. Angew. Chem. Int. Ed. Engl. 1992,32,1541. Also see Maehr, H. Tetrahedron Asymmetry 1992,3,735. 

A stereochemical drawing, once committed to paper, represents a specific stereoisomer. That is, the image defines the chirality sense of the object it depicts. Sometimes, chemists must convey information about structures whose absolute configurations may be unknown. For example, suppose we 

Effect of rotating the Fischer projection of 40c 180° about an axis perpendicular to the midpoint of the C2-C3 bond. 

The compound is usually drawn so that the main carbon skeleton is vertical and the highest priority functional group is at the top of the vertical line. 

This old-fashioned nomenclature is generally only used to show amino acids and sugars, which can contain several asymmetric centres (see Sections 11.1 and 11.3). 

S nomenclature can be assigned to Fischer projections by drawing the substituent of lowest priority in a vertical position (i.e. at the top). Although Fischer projections can be rotated in the plane of the paper by 180°, changing the position of substituents by 90° requires double exchanges . 

Examples (numbers on each carbon are given in italic to indicate priorities) 

It is sometimes useful to be able to draw a schematic diagram of the stereochemistry around a chiral carbon, especially when a molecule contains more than one chiral centre. The German chemist Emil Fischer solved this problem and his method of representing chiral centres is now called a Fischer projection. 

A Fischer projection looks like a cross, with the chiral centre at the point where the lines cross. The horizontal lines are considered to be bonds projecting towards the viewer, while the two vertical lines are considered to project away from the viewer. In this way the tetrahedral arrangement of 

Unfortunately, other nucleophiles can open a P-lactam ring and inactivate penicillins. Attack by water renders the penicillin unstable in aqueous solution (see Chapter 8 for more information) and some bacteria have evolved mechanisms to overcome penicillins and are said to be resistant to 

If two groups cannot be distinguished on the basis of atomic number, the next atom of the group attached to the chiral centre is considered, and so on until the priorities are clear. 

If a double- or triple-bonded group appears in the sequence, then each double bond is counted twice and each triple bond is counted three times, for example  

Stereochemistry deals with the three-dimensional arrangement of a molecule s atoms, and we have attempted to show stereochemistry with wedge-and-dash drawings and computergenerated models. It is possible, however, to convey stereochemical information in an abbreviated form using a method devised by the German chemist Emil Fischer. 

It is customary to orient the molecule so that the carbon chain is vertical with the lowest numbered carbon at the top as shown for the Fischer projection of (/ )-2-butanol. 

Ball-and-spoke models left), wedge-and-dash drawings center), and Fischer projections right) of the R and S enantiomers of bromochlorofluoromethane. 

To verify that the Fischer projection has the R configuration at its chirality center, rotate the three-dimensional representation so that the lowest-ranked atom (H) points away from you. Be careful to maintain the proper stereochemical relationships during the operation. 

With H pointing away from us, we can see that the order of decreasing precedence OH CH2CH3 CH3 traces a clockwise path, verifying the configuration as R. 

A Fischer (Real Life 5-2) projection is a simphfied way of depicting tetrahedral carbon atoms and their substituents in two dimensions. With this method, the molecule is drawn in the form of a cross, the central carbon being at the point of intersection. The horizontal lines signify bonds directed toward the viewer the vertical lines are pointing away. Hashed-wedged line structures have to be arranged in this way to facilitate their conversion into Fischer projections. 

Conversion of the Hashed-Wedged Line Structures of 2-Bromobutane into Fischer Projections (of the Stereocenter) 

Notice that just as there are several ways of depicting a molecule in the hashed-wedged line notation, there are several correct Fischer projections of the same stereocenter. 

The other isomer was called L-glyceraldehyde. All chiral compounds that could be converted into D-(+)-glyceraldehyde by reactions that did not affect the configuration at the stereocenter were assigned the d configuration, and their mirror 

In 1951, the Dutch crystallographer Johannes Bijvoet established the absolute configurations of these compounds by the X-ray diffraction analysis of a salt of tartaric acid, which had been correlated by chemical means with Fischer s sugars and, in turn, glycCTaldehyde. As Bijvoet states in his papa- (abbreviated), The result is that Emil Fischo- s convention. . . appears to answer the reality. Lucky guess  

Either by hand or by computer, it s reasonably easy to draw and manipulate real stereochemical representations of molecules with two chiral centers, sometimes even with three. However, many biological molecules have many more chiral centers than this, and Fischer devised a way of representing these in a flat form, in which it is easy to see stereochemical relationships and, particularly, to identify meso-compounds. Fischer projections consist of a cross motif, 7.89, and in this, groups b and d are pointing toward us, out of the paper, while groups a and c point away from us, behind the paper. 

This type of projection is particularly useful in looking at the stereochemistry of sugars, such as glucose, 7.90 although it is simply a formalism, and not a likely conformation for the molecule, it is still a useful shorthand. If ribose, 7.91, is oxidized, 7.92 is obtained. The fact that this is a 

Assign an absolute configuration for each of the chiral centers of arabinose  

This is not quite as easy as for a single asymmetric carbon atom, and we will need to work on each of the centers separately. They are labeled 2, 3, and 4 as follows (in numbering the chain, the aldehyde takes precedence over the alcohols)  

We need to place group 4 at the top of the diagram, by swapping 2 and 4 to give 

We have been using dashed lines and wedges to indicate perspective in drawing the stereochemistry of asymmetric carbon atoms. When we draw molecules with several asymmetric carbons, perspective drawings become time-consuming and cumbersome. In addition, the complicated drawings make it difficult to see the similarities and differences in groups of stereoisomers. 

At the turn of the twentieth century, Emil Fischer was studying the stereochemistry of sugars (Chapter 23), which contain as many as seven asymmetric carbon atoms. To draw these structures in perspective would have been difficult, and to pick out minor stereochemical differences in the drawings would have been nearly impossible. Fischer developed a symbolic way of drawing asymmetric carbon atoms, allowing them to be drawn rapidly. The Fischer projection also facilitates comparison of stereoisomers, holding them in their most symmetric conformation and emphasizing any differences in stereochemistry. 

Perspective in a Fischer projection. The Fischer projection uses a cross to represent an asymmetric carbon atom. The horizontal lines project toward the viewer, and the vertical lines project away from the viewer. 

For each set of examples, make a model of the first structure, and indicate the relationship of each of the other structures to the first structure Examples of relationships same compound, enantiomer, structural isomer. 

In working Problem 5-16, you may have noticed that Fischer projections that differ by a 180° rotation are the same. When we rotate a Fischer projection by 180°, the vertical (dashed line) bonds still end up vertical, and the horizontal (wedged) lines still end up horizontal The horizontal lines forward, vertical lines back convention is maintained. 

The reaction between a carboxylic acid (an acid) and an amine (a base) results in the formation of a salt. The product salts are diastereomers (R,S and S,S) and can be separated by various methods. 

Most commonly, fractional recrystallization is employed to sep-separate arate the mixture. Usually, only one of the diastereomers is ob- 

A strong acid, such as HCI, is used to protonate the carboxylate anion, regenerating the carboxylic acid. 

Another method that is becoming very important is chromatography using a chiral phase. Often, a chiral stationary phase, prepared by covalently bonding a chiral compound to the surface of silica beads, is used. 

An understanding of the three-dimensional structures of molecules has played an important part in the development of organic chemistry. The first experiments of importance to this area were reported in 1815 by the French physicist J. B. Biot, who discovered that certain organic compounds, such as turpentine, sugar, camphor, and tartaric acid, were optically active that is, solutions of these compounds rotated the plane of polarisation of plane-polarized light. Of course, the chemists of this period had no idea of what caused a compound to be optically active because atomic theory was just being developed and the concepts of valence and stereochemistry would not be discovered until far in the future. 

Since its introduction in 1956, the Cahn-Ingold-Prelog system has become the standard method of stereochemical notation. 

Fischer was the foremost organic chemist of the late nineteenth century. Fie won the 1902 Nobel Prize in chemistry for his pioneering work in carbohydrate and protein chemistry. 

Edward Siloac, an undergraduate organic chemistry student at the University of Virginia, published a paper in the June 1999 issue of the Journal of Chemical Education (pp. 798-799) that described how to use your hands to translate Fischer projections to R and S configurations. 

When learning to visualize chiral molecules, it s best to begin by building molecular models. As more experience is gained, it becomes easier to draw pictures and work with mental images. To do this successfully, though, a standard method of representation is needed for depicting the three- 

PRACTICE the skill 5.26 Draw all possible stereoisomers for each of the following compounds. Each possible stereoisomer should be drawn only once  

27 There are only two stereoisomers of 1,4-dimethylcyclohexane. Draw them, and explain why only two stereoisomers are observed. 

28 How many stereoisomers do you expect for the following compound Draw all of the stereoisomers. 

Fischer projections are primarily used for analyzing sugars (Chapter 24). In addition, Fischer projections are also helpful for quickly comparing the relationship between stereoisomers  

When the lowest ranked substituent (the methyl group) is away from us, the order of decreasing precedence of the remaining groups must appear in a clockwise sense in the R enantiomer. 

The Cahn-Ingold-Prelog system is the standard method of stereochemical notation. It replaced an older system based on analogies to specified reference compounds that used the prefixes d and l, a system that is still used for carbohydrates and amino acids. We will use d and l notation when we get to Chapters 23-26, but won t need it until then. 

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Fischer projection A method of representing three-dimensional structures in two-dimensional drawings in which the chiral atom(s) lies in the plane of the paper. The two enantiomeric forms of glyceraldehyde are represented as... 

Lei s relurn fo bromochlorofluoromelhane as a simple example of a chiral mole cule The Iwo enanliomers of BrClFCH are shown as ball and slick models as wedge and dash drawings and as Fischer projections m Figure 7 6 Fischer projeclions are always generated Ihe same way Ihe molecule is oriented so lhal Ihe verlical bonds al Ihe chiralily center are directed away from you and Ihe horizonlal bonds poinl toward you A projeclion of Ihe bonds onto Ihe page is a cross The chiralily center lies al Ihe center of Ihe cross bul is nol explicilly shown... 

What IS the absolute configuration (/ or S) of the compound rep resented by the Fischer projection shown here ... 

As you work with Fischer projections you may notice that some routine structural changes lead to predictable outcomes—outcomes that may reduce the number of manip ulations you need to do to solve stereochemistry problems Instead of listing these short cuts Problem 7 10 invites you to discover some of them for yourself... 

Using the Fischer projection of (/ ) 2 butanol that was given at... 

Switching the positions of two groups in a Fischer projection reverses the config ration of the chirality center... 

We mentioned in Section 7 6 that the d l system of stereochemical notation while outdated for most purposes is still widely used for carbohydrates and amino acids Likewise Fischer projections find their major application m these same two families of compounds... 

FIGURE 7 9 Repre sentations of (2/ 3R) dihy droxybutanoic acid (a) The staggered conformation is the most stable but is not properly arranged to show stereochemistry as a Fischer projection (b) Rotation about the C 2-C 3 bond gives the eclipsed conforma tion and projection of the eclipsed conformation onto the page gives (c) a correct Fischer projection... 

Fischer projections of the stereoisomeric 2 3 dihydroxybutanoic acids compounds I and II are erythro stereoisomers and III and IV are threo... 

Draw Fischer projections or make molecular models of the four stereoisomeric 3 ammo 2 butanols and label each erythro or threo as appropriate... 

Fischer projection formulas can help us identify meso forms Of the three stereoisomeric 2 3 butanediols notice that only in the meso stereoisomer does a dashed line through the center of the Fischer projection divide the molecule into two mirror image halves... 

When using Fischer projections for this purpose however be sure to remember what three dimensional objects they stand for One should not for example test for superim position of the two chiral stereoisomers by a procedure that involves moving any part of a Fischer projection out of the plane of the paper in any step... 

The separation of a racemic mixture into its enantiomeric components is termed resolution The first resolution that of tartaric acid was carried out by Louis Pasteur m 1848 Tartaric acid IS a byproduct of wine making and is almost always found as its dextrorotatory 2R 3R stereoisomer shown here m a perspective drawing and m a Fischer projection... 

Construct a molecular model corresponding to the Fischer projection of rneso 2 3 dibro mobutane Convert this molecular model to a staggered conformation in which the bromines are anti to one another Are the methyl groups anti or gauche to one another in this staggered con formation" ... 

Write the Fischer projection of the (-) 2 octanol formed from it by nucleophilic substitution with inversion of configuration... 

Make a molecular model corresponding to the stereochem istry of the Fischer projection of 2 phenyl 2 butanol shown in the equation and verify that it has the R configuration... 

FIGURE 25 1 Three dimensional representations and Fischer projections of the enantiomers of glycer aldehyde... 

Fischer projections and d-l notation have proved to be so helpful m representing carbohydrate stereochemistry that the chemical and biochemical literature is replete with their use To read that literature you need to be acquainted with these devices as well as the more modern Cahn-Ingold-Prelog R S system... 

The aldotetroses are the four stereoisomers of 2 3 4 trihydroxybutanal Fischer pro jections are constructed by orienting the molecule m an eclipsed conformation with the aldehyde group at the top The four carbon atoms define the mam chain of the Fischer projection and are arranged vertically Horizontal bonds are directed outward vertical bonds back... 

Relative to each other both hydroxyl groups are on the same side m Fischer pro jections of the erythrose enantiomers The remaining two stereoisomers have hydroxyl groups on opposite sides m their Fischer projections They are diastereomers of d and L erythrose and are called d and l threose The d and l prefixes again specify the con figuration of the highest numbered chirality center d Threose and l threose are enan tiomers of each other... 

Which aldotetrose is the structure shown Is it D erythrose D threose L erythrose or L threose (Be careful The conformation given is not the same as that used to generate a Fischer projection)... 

Once the eight Fischer projections have been written they are named m order with the aid of the sentence All altruists gladly make gum m gallon tanks The words of the sentence stand for allose altrose glucose mannose gulose idose galactose talose... 

Aldoses exist almost exclusively as their cyclic hemiacetals very little of the open chain form is present at equilibrium To understand their structures and chemical reac tions we need to be able to translate Fischer projections of carbohydrates into their cyclic hemiacetal forms Consider first cyclic hemiacetal formation m d erythrose To visualize furanose nng formation more clearly redraw the Fischer projection m a form more suited to cyclization being careful to maintain the stereochemistry at each chirality center... 

Substituents that are to the right m a Fischer projection are down m the corre spondmg Haworth formula those to the left are up... 

How many ketotetroses are possible Write Fischer projections... 

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