Using the Cambridge Structural Database for Teaching

Home , Aromaticity, Conjugated system, Hapticity, Pi backbonding

USING THE CAMBRIDGE STRUCTURAL DATABASE FOR TEACHING

CSDS Teaching Modules 2 CSDS Teaching Modules Conditions of Use

The Cambridge Structural Database System (CSD System) comprising all or some of the following: ConQuest, Quest, PreQuest, Mercury, (Mercury CSD and Materials Module of Mercury), VISTA, Mogul, IsoStar, SuperStar, web accessible CSD tools and services, WebCSD, CSD Java sketcher, CSD data file, CSD-UNITY, CSD-MDL, CSD-SDfile, CSD data updates, sub files derived from the foregoing data files, documentation and command procedures (each individually a Component) is a database and copyright work belonging to the Cambridge Crystallographic Data Centre (CCDC) and its licensors and all rights are protected. Use of the CSD System is permitted solely in accordance with a valid Licence of Access Agreement and all Components included are proprietary. When a Component is supplied independently of the CSD System its use is subject to the conditions of the separate licence. All persons accessing the CSD System or its Components should make themselves aware of the conditions contained in the Licence of Access Agreement or the relevant licence.

In particular: • The CSD System and its Components are licensed subject to a time limit for use by a specified organisation at a specified location. • The CSD System and its Components are to be treated as confidential and may NOT be disclosed or re- distributed in any form, in whole or in part, to any third party. • Software or data derived from or developed using the CSD System may not be distributed without prior written approval of the CCDC. Such prior approval is also needed for joint projects between academic and for-profit organisations involving use of the CSD System. • The CSD System and its Components may be used for scientific research, including the design of novel compounds. Results may be published in the scientific literature, but each such publication must include an appropriate citation as indicated in the Schedule to the Licence of Access Agreement and on the CCDC website. • No representations, warranties, or liabilities are expressed or implied in the supply of the CSD System or its Components by CCDC, its servants or agents, except where such exclusion or limitation is prohibited, void or unenforceable under governing law.

Licences may be obtained from:

Cambridge Crystallographic Data Centre 12 Union Road Cambridge CB2 1EZ United Kingdom

Web: http://www.ccdc.cam.ac.uk Telephone: +44-1223-336408 Email: [email protected]

(UNITY is a product of Tripos, L.P. and MDL is a registered trademark of Elsevier MDL)

1 INTRODUCTION

This booklet contains a series of step-by-step exercises that utilise the Cambridge Structural Database to assist and enhance the teaching of many of the concepts encountered in a typical undergraduate chemistry curriculum.

Crystal structure analyses are remarkable for the richness of structural information they provide. Both the 3D geometric structures of molecules and also the nature and geometry of their interactions with other molecules and ions are characterised. Integrate the use of crystal structure data into your course, visualise and manipulate molecules in 3D, and expose students to real experimental data.

• Non-subscribers : A number of the exercises presented here draw exclusively from a free 500- structure teaching subset of the Cambridge Structural Database, and thus do not require a CSD licence, see TEACHING SUBSET OF THE CSD (see page 6). • CSD licence holders : Providing your institution holds at least one CSDS licence then you can install as many copies of Classroom ConQuest as you require for group teaching purposes. This will allow your students to fully utilise the search and analyses capabilities of the CSD, see: CLASSROOM CONQUEST (see page 7).

This booklet is also present in the top level of the UNIX , Windows, and MacOSX software DVD- ROMs as both HTML and PDF files should you require additional copies.

teaching_examples.html teaching_examples.pdf

Alternatively, these and other CSD System teaching examples can be accessed via the CCDC website at the following address:

http://www.ccdc.cam.ac.uk/free_services/teaching/

CSDS Teaching Modules 2 TEACHING SUBSET OF THE CSD

A free 500-structure teaching subset of the Cambridge Structural Database is available as a download from the following URL:

http://www.ccdc.cam.ac.uk/free_services/teaching/

The subset has been specifically designed to provide a wide diversity of chemical content and includes many of the key molecules typically used to exemplify the chemical concepts taught in undergraduate courses. The subset is provided in CSD-database format and can be viewed using our free crystal structure visualisation program Mercury, see: http://www.ccdc.cam.ac.uk/free_services/ mercury/

A number of the teaching exercise presented here draw exclusively from the teaching subset and thus do not require a CSDS licence, whilst others will require access to the full database and associated search tools. For further information, see TEACHING MODULES (see page 8).

The free 500-structure subset is based upon work supported by the United States National Science Foundation under Grant No. 0725294.

6 CSDS Teaching Modules 3 CLASSROOM CONQUEST

Classroom ConQuest is a version of ConQuest which has been designed for group teaching activities.

• Anyone with at least one normal ConQuest licence can install as many copies of Classroom ConQuest as they require. • It has all the functionality of normal ConQuest with the limitation that searches can only be done on a subset of entries. • The subset of entries can either be the default selection supplied with Classroom ConQuest or one derived by the user from the main CSD.

In order to install Classroom ConQuest you must first obtain a Classroom ConQuest Validation Number from the CCDC. Please contact the CCDC with your Site Code and Confirmation Code using:

Email: [email protected]

Note : Classroom ConQuest licences do not allow access to Mogul or Mercury CSD.

CSDS Teaching Modules 4 TEACHING MODULES

AROMATICITY (see page 9) SHAPES OF MOLECULES: VSEPR MODEL (see page 18) METAL CARBONYL BACK-BONDING (see page 28) * DETERMINING MOLECULAR DIMENSIONS (see page 39) * ANALYSING 4-COORDINATE METAL GEOMETRY (see page 47) * REACTION INTERMEDIATES: HALONIUM IONS (see page 60) * HAPTICITY (see page 67) CONFORMATIONS OF RINGS (see page 77) STEREOCHEMISTRY (see page 89)

Other teaching exercises and resources are available from:

http://www.ccdc.cam.ac.uk/free_services/teaching/

* these exercises require full access to the Cambridge Structural Database System

8 CSDS Teaching Modules 5 AROMATICITY

5.1 INTRODUCTION • The word aromatic can be used to describe fragrant substances such as benzaldehyde (from cherries, almonds), and toluene (from Tolu balsam). • However, in the early nineteenth century such substances were discovered to behave in a different chemical manner from other organic compounds. Thus, in chemistry, the term aromatic is now used to refer to benzene and it’s structural relatives. • The Cambridge Structural Database can be used to explore the structural requirements for aromaticity. By investigating the structure of such compounds we can explain their special stability.

5.2 OBJECTIVES • To investigate the concept of aromaticity by analysing experimental crystal structure data. • To determine the structural requirements for aromaticity by examining a series of benzene and cyclooctatetraene derivatives. • To understand the reason for the observed stability of benzene in terms of its molecular orbital description. • To use your findings to predict whether or not certain given compounds are aromatic.

5.3 GETTING STARTED • If you do not subscribe to the Cambridge Structural Database (CSD) System: • Open free Mercury (the free version of Mercury can be downloaded from http:// www.ccdc.cam.ac.uk/free_services/mercury/ ) • Open the free teaching subset of the CSD (downloadable from http://www.ccdc.cam.ac.uk/ free_services/teaching/downloads ) by selecting File from the top-level menu, followed by Open in the resulting menu, and then selecting the database file teaching_subset.ind • Database reference codes ( refcodes ) of the structures in the teaching database will appear in a list on the right hand side of the main Mercury window. To view a structure select the corresponding refcode in the list. • Once the teaching database has been loaded Mercury can then read text files containing lists of database reference codes ( refcodes ). To read in a file containing just those structures required for this tutorial hit File in the top-level menu, followed by Open , then select the file aromaticity.gcd. • If you subscribe to the Cambridge Structural Database (CSD) System: • Open MercuryCSD. • The full database should be detected and opened within the Structure Navigator on the right hand side of the main Mercury window.

CSDS Teaching Modules • Once a database has been loaded Mercury can then read text files containing lists of database reference codes ( refcodes ). To read in a file containing just those structures required for this tutorial hit File in the top-level menu, followed by Open , then select the file vsepr.gcd. • Within the Structure Navigator loaded crystal structures are presented in a hierarchical tree organised first by file type ( Databases , Structures , Refcode Lists , ConQuest Hits , or Mercury Files ) and subsequently by filename and then by individual refcode . The file aromaticity.gcd can be found under Refcode Lists . To view a structure select the corresponding refcode .

5.4 STEPS REQUIRED

5.4.1 Examine the structure of benzene • Benzene (a) is unusually stable for an alkene. Normal alkenes readily react with bromine to give dibromoalkane addition products [1]. However, benzene reacts only in the presence of a Lewis acid catalyst and the product is a monosubstituted benzene not an addition product [2]. Why does benzene not behave like other alkenes?

Br Br2 [1] Br

Br Br 2/AlCl 3 [2]

(a)

• Display the structure of benzene by clicking on the identifier BENZEN02 from the Structure Navigator on the right hand side of the main Mercury window. • Inspect the structure. You will notice that benzene is a planar symmetrical hexagon (internal bond angles close to 120 degrees) with six trigonal ( sp 2) carbon atoms, each with one hydrogen atom in the plane of the ring.

To manipulate structures in Mercury

1. Structures can be rotated by moving the cursor in the display area while keeping the left-hand mouse button pressed down.

2. To zoom in and out move the cursor up and down in the display area while keeping the right-hand

10 CSDS Teaching Modules mouse button pressed down.

3. To translate structures hold down the middle mouse button while moving the cursor in the display area (three-button mouse only). Alternatively, move the cursor in the display area while keeping both the left-hand mouse button and the keyboard Ctrl key pressed down.

4. At any stage the display area can be returned to the default view by hitting the Reset button at the bottom of the window.

• Next, measure each of the carbon-carbon bond lengths in the structure. You will see that all bond lengths are around 1.38Å. How does this compare to typical carbon-carbon double and single bond lengths? Typical C=C double bonds are 1.33Å and C-C single bonds are 1.46Å.

To measure distances in Mercury

1. Set Picking Mode in the tool bar (near the top of the main Mercury window) to the required parameter type, viz. Measure Distance , Measure Angle or Measure Torsion

2. Geometrical measurements (intramolecular or intermolecular) can now be made by clicking on e.g., two atoms for a distance, three atoms for an angle or four atoms for a torsion angle.

3. To remove all geometrical measurements from the display click on the Clear Measurements button in the tool bar near the top of the main Mercury window.

5.4.2 Examine the structure of cyclooctatetraene. • Cyclooctatetraene (shown below) has four double bonds in a ring, what do you think its 3D structure will be?

• Display the structure of cyclooctatetraene by selecting the identifier ZZZSAE01 from the Structure Navigator . • Inspect the structure. You will notice that unlike benzene, cyclooctatetraene is not planar, instead it adopts a “ tub ” shape. The reason for this lack of planarity is that a regular octagon has internal angles of 135 degrees, while sp 2 angles are most stable at 120 degrees. To avoid the strain the molecule therefore adopts a nonplanar geometry.

CSDS Teaching Modules • Measure each of the carbon-carbon bond lengths in the structure. There are two carbon-carbon bond lengths: 1.46Å and 1.33Å. These are typical for double and single carbon-carbon bonds. • Chemically speaking, cyclooctatetraene behaves like an alkene not like benzene e.g. it does not form a substitution product with bromine, but an addition product. • Why is benzene so different from other alkenes and why is cyclooctatetraene different from benzene?

5.4.3 Consider what happens when we treat cyclooctatetraene with a powerful reducing agent • If 1,3,5,7-tetramethylcyclooctatetraene (refcode TMCOTT ) is treated with alkali metals a dianion is formed (refcode TMOCKE ). • Look closely at the structures of 1,3,5,7-tetramethylcyclooctatetraene (refcode TMCOTT ) and the resultant dianion (refcode TMOCKE ). How do these two compounds differ structurally? • The dianion is planar and all bonds lengths are equivalent (within experimental error). Whereas the neutral compound is non-planar (“ tub” shaped) with alternate double and single bonds lengths of 1.48Å and 1.33Å.

left: “tub” shape of 1,3,5,7-tetramethylcyclooctatetraene (refcode TMCOTT); right: the resulting planar dianion (refcode TMOCKE)

• By reducing 1,3,5,7-tetramethylcyclooctatetraene we are adding electrons. The difference between the anion and the neutral compound is therefore the number of electrons in the π system. The following table summarises what we have discovered so far:

12 CSDS Teaching Modules Compound and CSD Diagram π Electrons Geometry Refcode

cyclooctatetraene 8 non-planar ZZZSAE01

1,3,5,7-tetramethyl 8 non-pla- cyclooctatetraene nar

TMCOTT

1,3,5,7-tetramethyl 10 planar cyclooctatetraene dianion

TMOCKE

5.4.4 Consider what happens if we treat benzene with oxidizing or reducing agents

• Treatment of benzene with strongly oxidising SbF 5/SO 2ClF has no effect. However, it is possible to oxidise substituted derivatives. Hexakis(dimethylamino)benzene (refcode GENFAG ) can be oxidised with iodine to give the dication (refcode GENFEK ). • Compare these two structures. This time you will notice that, unlike the neutral compound, the cation is nonplanar and all carbon-carbon bonds lengths are not the same. • Similar results are obtained when we reduce hexakis(trimethylsilyl)benzene (refcode KELVOM ) to the dianion (refcode KINFUI ). Again, compare these two structures, how do they differ? • Clearly the number of π electrons is important in determining whether or not cyclic alkenes adopt a planar geometry. Complete the table below with your findings:

CSDS Teaching Modules Compound and CSD Diagram π Electrons Geometry Refcode

benzene 6 planar

BENZEN02

hexakis(dimethy 6 amino) benzene

GENFAG

hexakis(dimethy amino) benzene dication

GENFEK

hexakis(trimethylsi- planar lyl) benzene

KELVOM

hexakis(trimethylsilyl) benzene dianion,

KINFUI

14 CSDS Teaching Modules 5.4.5 Do you see a pattern forming? • The number of π electrons in the system is crucial: when they have 4 or 8 π electrons both cyclooctatetraene and benzene adopt non-planar geometries; when they have 6 or 10 π electrons a conjugated planar geometry is preferred. • Remember: the planar 1,3,5,7-tetramethylcyclooctatetraene dianion (refcode TMOCKE ) still has considerable ring strain. The fact that this structure adopt a planar geometry must mean that there is some other form of stabilization (gained as a results of having 10 π electrons) that outweights the strain of being planar. The extra stability is called aromaticity.

5.4.6 Molecular orbital description • The special stability (aromaticity) of benzene comes from having six π electrons. These six electrons fully occupy the three molecular bonding orbitals and are therefore delocalised over the entire conjugated system. This closed shell structure is the reason for the observed stability of benzene.

• By comparison, cyclooctatetraene has eight electrons, six of these fill the molecular bonding orbitals and two occupy the degenerate pair of non-bonding orbitals.

• Cyclooctatetraene must therefore lose or gain 2 electrons in order to have a closed shell structure. We have seen this already: the 1,3,5,7-tetramethyl-cyclooctatetraene dianion is planar, allowing delocalisation over the ring, whereas the neutral structure adopts a nonplanar tub shape with localised bonds. • Look at the MO level diagrams above. There is always a single low-energy bonding orbital followed by pairs of degenerate orbitals. Since the single orbital will hold two electrons when

CSDS Teaching Modules full and the degenerate pairs four, we will only have a closed shell of electrons in these π orbitals when they contain 4n+2 electrons.

5.4.7 Requirements for aromaticity • We can now summarizes what we have discovered: A molecule can only be aromatic if it has a planar (so that p-orbitals can overlap) system of conjugation with 4n+2 π electrons (where n = 0, 1, 2, 3...) i.e. only molecules with 2, 6, 10, 14, 18... π electrons can be aromatic. • This is the basis for Huckels Rule, which states “Planar, fully conjugated, monocyclic systems with 4n+2 π electrons ( n = 0, 1, 2, 3...) have a closed shell of electrons all in bonding orbitals and are exceptionally stable. Such systems are said to be aromatic”

5.4.8 Use Huckels rule to predict aromaticity • Determine which of the following compounds are aromatic. Examine the structures to see whether or not they are planar and fully conjugated. Justify your answers with some electron counting: • tetra-t-butyl-cyclobutadiene ( TBUCBD10 ) • naphthalene ( NAPHTA12 ) • cyclohepta-1,3,5-triene ( CHMOCO01 ) • cyclopentadienyl anion ( NARGET ) • (14)annulene ( FANNUL ) • (16)annulene ( ANNUL01 ) • (18)annulene ( ANULEN ) • pyridine ( PYRDNA01 )

5.5 SUMMARY OF KEY CONCEPTS • Benzene is a cyclic, planar, conjugated molecule. All carbon-carbon bonds are equivalent and have a length of 1.38Å, a value between that of normal carbon single- and double-bond lengths. • Benzene is unusually stable. It reacts slowly with electrophiles to give substitution products in which cyclic conjugation is retained. This stability comes from having 4n+2 π electrons (where n = 1). These six electrons fully occupy the three molecular bonding orbitals and are therefore delocalised over the entire conjugated system. This closed shell structure is the reason for the observed stability of benzene. • A molecule can only be aromatic if it has a planar (so that p-orbitals can overlap) system of conjugation with 4n+2 π electrons. This is the basis for Huckels rule. • Other kinds of molecules can also be aromatic according to the Huckel definition. For example, the 1,3,5,7-tetramethyl-cyclooctatetraene dianion (TMOCKE ) and the cyclopentadienyl anion (NARGET) are both aromatic ions. Heterocyclic compounds can also be aromatic, for example

16 CSDS Teaching Modules pyridine ( PYRDNA01 ) is a six-membered nitrogen-containing heterocycle and resembles benzene electronically.

CSDS Teaching Modules 6 SHAPES OF MOLECULES: VSEPR MODEL

6.1 INTRODUCTION • The shapes of molecules tend to be controlled by the number of electrons in the valence shell of the central atom. The valence-shell electron-pair repulsion (VSEPR) model provides a simple method for predicting the shapes of such species. • The Cambridge Structural Database contains a wealth of diverse molecular geometries, and provides the ability to visualise and manipulate molecules in three-dimensions. This is vitally important in order to study and understand the shapes adopted by particular molecules.

6.2 OBJECTIVES • To investigate shapes of molecules by analysing experimental crystal structure data. • To understand the factors that determine the preferred shape adopted by particular molecules. • To use the valence-shell electron-pair repulsion (VSEPR) model to predict the shapes of given molecules.

6.3 GETTING STARTED • If you do not subscribe to the Cambridge Structural Database (CSD) System: • Open free Mercury (the free version of Mercury can be downloaded from http:// www.ccdc.cam.ac.uk/free_services/mercury/ ) • Open the free teaching subset of the CSD (downloadable from http://www.ccdc.cam.ac.uk/ free_services/teaching/downloads ) by selecting File from the top-level menu, followed by Open in the resulting menu, and then selecting the database file teaching_subset.ind • Database reference codes ( refcodes ) of the structures in the teaching database will appear in a list on the right hand side of the main Mercury window. To view a structure select the corresponding refcode in the list. • Once the teaching database has been loaded Mercury can then read text files containing lists of database reference codes ( refcodes ). To read in a file containing just those structures required for this tutorial hit File in the top-level menu, followed by Open , then select the file vsepr.gcd. • If you subscribe to the Cambridge Structural Database (CSD) System: • Open MercuryCSD. • The full database should be detected and opened within the Structure Navigator on the right hand side of the main Mercury window. • Once a database has been loaded Mercury can then read text files containing lists of database reference codes ( refcodes ). To read in a file containing just those structures required for this tutorial hit File in the top-level menu, followed by Open , then select the file vsepr.gcd. • Within the Structure Navigator loaded crystal structures are presented in a hierarchical tree

18 CSDS Teaching Modules organised first by file type ( Databases , Structures , Refcode Lists , ConQuest Hits , or Mercury Files ) and subsequently by filename and then by individual refcode . The file vsepr.gcd can be found under Refcode Lists . To view a structure select the corresponding refcode .

6.4 STEPS REQUIRED

6.4.1 Examine the structures of di-, tri-, and tetrachloro mercury - 2- • Consider the following series of molecules: HgCl 2, HgCl 3 , and HgCl 4 as we move across the series we are successively adding a Cl to the central Hg atom. For each structure how would you expect the Cl atoms to arrange themselves around the Hg atom? Sketch each of the structures to show the shape of the molecule you predict. • Check you answers by inspecting the corresponding crystal structures. The following structures - 2- are provided: HgCl 2 (refcode OKAJOZ ), HgCl 3 (refcode KUSMAM ), and HgCl 4 (refcode KEYZUK ). To display a structure click on the identifier in the Structure Navigator on the right hand side of the main Mercury window.

To manipulate structures in Mercury

1. Structures can be rotated by moving the cursor in the display area while keeping the left-hand mouse button pressed down.

2. To zoom in and out move the cursor up and down in the display area while keeping the right-hand mouse button pressed down.

4. At any stage the display area can be returned to the default view by hitting the Reset button at the bottom of the window.

• Do the shapes of the experimentally determined structures agree with your predictions? For each of the three structures measure the Cl-Hg-Cl bond angles in the structure. What does this tell you about the observed geometries?

To measure angles in Mercury

1. Set Picking Mode in the tool bar (near the top of the main Mercury window) to the required parameter type, viz. Measure Distance , Measure Angle or Measure Torsion

CSDS Teaching Modules 2. Geometrical measurements (intramolecular or intermolecular) can now be made by clicking on e.g., two atoms for a distance, three atoms for an angle or four atoms for a torsion angle.

3. To remove all geometrical measurements from the display click on the Clear Measurements button in the tool bar near the top of the main Mercury window.

- • HgCl 2 is linear with bonds angles of 180 deg., HgCl 3 exists in a trigonal planar arrangement 2- with bond angles of approximately 120 deg., and HgCl 4 is tetrahedral with all bond angles approaching 109.5 deg. What is the main factor that determines the geometry that is adopted?

- 2- Image: showing HgCl 2 (linear), HgCl 3 (trigonal planar), and HgCl 4 (tetrahedral).

6.4.2 The VSEPR model • The valence-shell electron pair repulsion (VSEPR) model is used for predicting molecular shape. The primary assumption of the VSEPR model is that regions of enhanced electron density (i.e. bonding pairs, lone pairs and multiple bonds) take up positions as far apart as possible so that the repulsions between them are minimised.

• Thus, in a molecule EX n, there is a minimum energy arrangement for a given number of electron pairs. For example, in HgCl 2 repulsions between the two electron pairs in the valence shell of Hg - are minimised if the Cl-Hg-Cl unit is linear. In HgCl 3 electron-electron repulsions are minimised if a trigonal planar arrangement of electron pairs (and thus Cl atoms) is adopted. The table below shows the minimum energy arrangements and ideal bond angles for EX n molecules (where n = 2- 8).

Formula Number of Shape Spatial Arrangement Ideal Bond Angle EX n Electron pairs (deg.)

EX 2 2 Linear 180

20 CSDS Teaching Modules Formula Number of Shape Spatial Arrangement Ideal Bond Angle EX n Electron pairs (deg.)

EX 3 3 Trigonal planar 120

EX 4 4 Tetrahedral 109.5

EX 5 5 Trigonal bipy- Xax-E-Xeq = 90 ramidal Xeq-E-Xeq = 120

EX 6 6 Octahedral X1-E-X 2 = 90

EX 7 7 Pentagonal bipy- Xax-E-Xeq = 90 ramidal Xeq-E-Xeq = 72

CSDS Teaching Modules Formula Number of Shape Spatial Arrangement Ideal Bond Angle EX n Electron pairs (deg.)

EX 8 8 Square Antipris- X1-E-X 2 = 78 matic X1-E-X 3 = 73

6.4.3 Apply the VSEPR model to predict basic shape • The VSEPR model can be applied systematically by following a few simple steps. As an - example we will consider the structure of hexafluorophosphate, [PF 6] . - • First, draw the Lewis structure of the molecule and identify the central atom. For [PF 6] the central atom is a phosphorus.

• Next, determine the number of valence electrons on the central atom. Phosphorus has the electron configuration: 1s 22s 22p 63s 23p 3 and thus has 5 valence electrons. Add to this the - number of electrons that are contributed by all directly bonded atoms. For [PF 6] there are 6 fluorine atoms, each contributing 1 electron. Finally, we add one electron to account for the single negative charge on the phosphorus. This brings our total to 12. • Divide this number by 2 to give the total number of electron pairs (i.e. 6) and assign the coordination geometry corresponding to this number using the table in the previous section. - • Hexafluorophosphate, [PF 6] therefore has an octahedral geometry. To summarise:

22 CSDS Teaching Modules - hexafluorophosphate, [PF 6] . Central atom: phosphorus Valence electrons on central atom: 5 6 F atoms, each contribute 1 electron: 6 Add 1 for negative charge on phosphorus 1 Total: 12 Divide by 2 to give electron pairs: 6 6 electron pairs: Octahedral geometry for the 6 shape- determining electron pairs

• Check this for yourself by examining the crystal structure of this molecule (CSD refcode WINFAA ). Measure the F-P-F bond angles in the structure and see how they correspond to the ideal octahedral angles given in the table in the previous section. • Apply the VSEPR model in order to predict the geometry of the following molecules. Confirm that your answers are correct by examining the corresponding crystal structures. Comment on how closely the observed bond angles agree with the expected ideal values. - • [BrF 6] : CSD refcode ZAQBIC - • [I 3] : CSD refcode RIKTAG

• In(CH 3)3 : CSD refcode TRMEIN03 2- • [BeF 4] : CSD refcode KIPPEE + • [NH 4] : CSD refcode ACARBM01

• Fe(CO) 5 : CSD refcode FOJBOV01 - • [SbF 6] : CSD refcode FUJLAX

CSDS Teaching Modules 6.4.4 Modifications to basic shapes: considering the effect of lone pairs • The molecules you have encountered so far include only bonding pairs. How does the presence of lone pairs affect molecular shape? - • Consider the molecule [XeF 5] . Xe is in group 18 and possesses 8 electrons in its valence shell. There are 5 fluorine atoms, each contributing 1 electron, this brings our electron count to 13. Finally, we add one electron to account for the single negative charge on the Xe. This brings our total to 14. Again, we divide this number by 2 to give the total number of electron pairs (i.e. 7) The parent shape is therefore a pentagonal bipyramid. • However, once the basic shape of a molecule has been identified, adjustments must be made to account for the differences in electrostatic repulsion between bonding regions and lone pairs. Repulsions lie in the order:

lone pair/lone pair > lone pair/bonding pair > bonding pair/bonding pair

The greater repelling effect of a lone pair is explained by supposing that the lone pair is on average closer to the nucleus than a bonding pair and therefore repels other electrons more strongly. - • Thus for [XeF 5] the parent shape is a pentagonal bipyramid with the lone pairs opposite to each - other in order to minimise lone pair/lone pair repulsions. The [XeF 5] anion is therefore pentagonal planar.

• Check this for yourself by examining the crystal structure of this molecule (CSD refcode SOBWAH ). Measure the F-Xe-F bond angles in the structure and see how they correspond to the ideal angles given in the table in the previous section. • Next, examine in detail the crystal structures of di-bromodimethylselenium (CSD refcode RIZMIW ), and water (CSD refcode MUSIMO01 ). Can you explain the observed shapes of these two molecules in terms of the electrostatic repulsions present? • Di-bromodimethylselenium (CSD refcode RIZMIW ) has 5 electron pairs (4 bonding pairs, and 1

24 CSDS Teaching Modules lone pair), the parent shape is therefore trigonal-bipyramidal. Notice that the lone pair occupies the equatorial site in the trigonal-bipyramidal array. In the equatorial position the lone pair is repelled by two bonding pairs at 90 degrees, whereas in the axial position it would be repelled by 3 bonding pairs at 90 degrees. RIZMIW therefore adopts a disphenodial, or “see-saw” shape.

• Water (CSD refcode MUSIMO01 ) has 4 electron pairs (2 bonding pairs and 2 lone pairs). The parent shape is therefore tetrahedral and the molecule will adopt an angular, or “bent” shape. Notice that the HOH angle is decreased relative to that expected when all pairs are bonding. The two lone pairs repel each other more strongly and move apart thus forcing the HOH angle to be less than the ideal tetrahedral angle of 109.5 degrees.

• The table below shows the common shapes for EX n molecules (where n = 3-5) including the shapes adopted by molecules containing one or more lone pairs.

CSDS Teaching Modules Formula Shape EX n

EX 3

Trigonal Planar Trigonal Pyramidal T-Shaped

EX 4

Tetrahedral Square Planar See-Saw (Disphenodial)

EX 5

Pentagonal Planar Trigonal bipyramidal Square-Based Pyramidal

6.4.5 Further examples • Apply the VSEPR model in order to predict the geometry of the following molecules. Confirm that your answers are correct by examining the corresponding crystal structures. Comment on how closely the observed bond angles agree with the expected ideal values? Can you account for any deviation from the ideal values? • Sulfur dioxide: CSD refcode DADXOW 2- • [CeCl 6] : CSD refcode CLCAME01 • Dichloro-trifluoromethyl)iodine : CSD refcode COXYIX

26 CSDS Teaching Modules

• NH 3 : CSD refcode KATLAT • Dibromo-pentapyridyl-strontium(ii): CSD refcode TANWAG - • [BCl 4] : CSD refcode PETKAB • Dichloro-diphenyl-selenium: CSD refcode PHSECL01 • trans-bis(Isothiocyanato)-bis(trimethylphosphine)-nickel(ii): CSD refcode BAZSUR • Boric acid: CSD refcode JAGREP - • [ClF 4] : CSD refcode ROLSEQ • Pentaphenoxyphosphorane: CSD refocde PPHOXP 2- • [SbBr 5] : CSD refcode CLPYSB • tris(Acetonitrile)-trichloro-titanium acetonitrile: CSD refcode DUDKUI10 • bis(1,2,3,4,5,6,7,8-Octaethylporphyrinato-N,N,N,N)-cerium(iv): CSD refcode DURLUX

6.5 SUMMARY OF KEY CONCEPTS • The valence-shell electron pair repulsion (VSEPR) model is used for predicting molecular shape. The primary assumption of the VSEPR model is that regions of enhanced electron density (i.e. bonding pairs, lone pairs and multiple bonds) take up positions as far apart as possible so that the repulsions between them are minimised. • Once the basic shape of a molecule has been identified, adjustments must be made to account for the differences in electrostatic repulsion between bonding regions and lone pairs. Repulsions lie in the order:

lone pair/lone pair > lone pair/bonding pair > bonding pair/bonding pair

- Thus for [XeF 5] the parent shape is a pentagonal bipyramid with the lone pairs opposite to each - other in order to minimise lone pair/lone pair repulsions. The [XeF 5] anion is therefore pentagonal planar. • A deficiency of the VSEPR model is that it cannot be used to predict the actual bond angle adopted by the molecule. For example, the HOH angle in water is decreased relative to that expected when all 4 electron pairs are bonding. The two lone pairs repel each other more strongly and move apart thus forcing the HOH angle to be less than the ideal tetrahedral angle of 109.5 degrees.

CSDS Teaching Modules 7 METAL CARBONYL BACK-BONDING

7.1 INTRODUCTION • Metal carbonyls are formed by complexation of a transition metal atom with carbon monoxide. In some cases carbon monoxide is the only ligand bound to the metal e.g. Mo(CO) 6 (CSD reference code FUBYIK ) but generally the metal carbonyl contains a mix of ligands e.g. [Mo{1,2-(NH) 2C6H4}(CO) 2(PPh 3)2] (CSD reference code PEPCES ).

• The carbonyl ligand is versatile and can bond to the metal atom in a number of ways including in a bridging mode e.g. refcode PALSOK . However for the purposes of this example we are interested only in terminal carbonyls, the most common way in which carbonyls bind to metals. • In metal carbonyls it is found that there is a complementary effect whereby the stronger (i.e. shorter) the MC bond, the weaker (i.e. longer) the corresponding CO bond. • This effect is known as pi back-bonding. • The effect of pi back-bonding can be nicely illustrated by performing a search of the Cambridge Structural Database while the explanation for why pi back-bonding occurs is explained by considering the molecular orbitals (specifically the HOMO (highest occupied molecular orbital) and LUMO (lowest occupied molecular orbital)) involved in the MCO bonding.

7.2 OBJECTIVES • To search for molybdenum carbon monoxide complexes in the CSD using ConQuest and monitor the MoC and CO bond lengths. • To read the search results into Vista for further analysis. • To rationalise the search results based on electron counting and orbital considerations.

28 CSDS Teaching Modules 7.3 GETTING STARTED • This module requires full access to the Cambridge Structural Database System. Specifically, the following software components will be used: • ConQuest , for search and retrieval of crystal structure data. • Vista , for analysis of geometric data retrieved using ConQuest. • The file backbonding.gcd is provided and contains the reference codes (refcodes) just those crystal structures which are specifically referred to in this tutorial.

7.4 STEPS REQUIRED

7.4.1 Define a search for molybdenum carbon monoxide complexes • Start ConQuest and click on the Draw button on the left-hand side of the interface. This launches the sketcher window. • The carbon C atom will be selected by default. Introduce a C atom into the sketcher window by left-clicking with the mouse in the middle of the window. • We now need to draw an oxygen atom which is triply bonded to the C. In the atom list at the bottom of the sketcher, pick O, then move along to the Bond: pull down menu and select Triple . Go to the C atom in the sketcher. Left-click and keeping the left mouse button depressed, move the mouse to the right until you see a triple bond appear. Release the left mouse button, and an O atom will be drawn bonded to the C. • Now bond a molybdenum atom to the C atom using a single bond by clicking on the More button at the bottom of the sketcher and selecting Other Elements... . Pick Mo from the resultant periodic table, then click OK . Now change the bond style to Single using the Bond: pull down menu at the bottom of the sketcher window. Left-click on the C atom in the sketcher and keeping the mouse button depressed, move to the left until a single bond appears, at which point release the mouse button. • The resultant substructure will look like the following:

CSDS Teaching Modules 7.4.2 Define the relevant bond lengths of interest (the MoC and CO bonds) and apply some constraints • Click on the ADD3D button on the top left of the sketcher. A pop-up window will appear. Click on the Mo then the C atom: they will be selected and you will notice the pop-up dialogue updates to reflect what is selected, i.e. you can now click on Define next to Distance . Now that this bond length has been defined it will be monitored during the ConQuest search of the Cambridge Structural Database. • Define the CO bond in the same way, i.e. by selecting first the C atom then the O atom then by clicking Define: next to Distance . • Once you have defined both bond lengths, you will notice they are both recorded in the top right of the sketcher window.

30 CSDS Teaching Modules • Hit the Done button to close the Geometric Parameters window. • We now need to restrict the cyclicity of all three atoms to specify that they do not belong to cyclic systems (e.g. cyclic ligands in the case of the CO) or organometallic networks. • Go to the top level Atoms menu option and select Cyclicity from the resultant pull-down menu. We require the Mo, C and O atoms to be Acyclic , so select this from the menu. Now click on the Mo, C and O atoms, then hit the Done button to complete the definition.

CSDS Teaching Modules • We now need to restrict the coordination numbers of the C and O atoms to ensure they are not bonded to any other atoms. • Right-click on the C atom and pick Number of Bonded Atoms , then 2 from the resultant pull- down menus. This means that ConQuest will consider CSD entries where only the Mo and O atoms are bonded to the carbon. • Now right-click on the O atom, but this time pick 1 from the Number of Bonded Atoms pull- down menu. This means that the O atom will form no bonds other than to the C atom. • We also need to specify that the Mo atom is 6-coordinate. This is done in the same way as described above for C and O, i.e. right-click on the Mo atom then pick Number of Bonded Atoms then 6 from the resultant pull-down menus.

7.4.3 Set the search running and analyse the results • Hit the Search button at the bottom of the sketcher window then hit Start Search . • The search results (i.e. a list of CSD entries that contain a substructure that matches the one we’ve sketched) will be displayed in the View Results window. Scroll through the results list and inspect some of the hits. You will notice that some of the hits contain more than one occurrence of our defined fragment:

32 CSDS Teaching Modules i.e. in the example above, MUQBAB , there are 10 MoCO substructure matches in the complex, each with different MoC and CO distances. • We can scroll through each of the hits and view the values for the distances we’ve plotted individually, or alternatively we can read the search results into another software package for further analysis (e.g. Excel or Vista, the latter of which is distributed with the CSD System). • Click on the Analyse Hitlist button at the top of the hitlist and pick View in Vista .

• We can import a number of parameters into Vista for inspection (e.g. Rfactor, a measure of the quality of the structure determination) however we’re currently only interested in the parameters we’ve searched for, so hit the View in Vista button again. • The Vista interface will display the search results, i.e. the two distances and the associated CSD refcode. • Histograms (i.e. a plot of a geometric parameter versus its occurrence) or scattergrams (i.e. a plot of one parameter versus the other) can be plotted using Vista. • Generate a scattergram of the MoC distance versus the CO distance. This is done by selecting the grey tabs at the top of the DIST1 and DIST2 columns, then by hitting the Scattergram button in the Data Visualization section of the interface.

CSDS Teaching Modules • If the scattergram is not in the orientation shown above, hit the Flip Axes button. • What do you notice about the plot? There is a linear relationship between the MoC and the CO distances. • Plot a linear regression by hitting the Plot Options button, activating the Linear regression button, then hitting OK . This will make it apparent that as one distance increases, the other decreases.

7.4.4 Try and rationalise what you are seeing • Carry out an electron count on carbon monoxide, CO. It has 10 electrons, 6 of which are involved in bonding. The remaining 4 are divided between the C and the O atom, meaning the C atom has 2 electrons for metal bonding (note that the following is only one of the resonance forms of carbon monoxide).

34 CSDS Teaching Modules • Thus the C is bonded to the Mo via a sigma bond; the lone pair on the C is donated to an empty metal sigma orbital:

• There is a secondary bonding effect: the Mo atom is 6-coordinate and is d6, thus the orbital splitting diagram will resemble the following:

i.e. the t 2g orbitals are filled however the e g orbitals are empty. • The donation of electrons from the CO to the metal via the sigma bond effectively increases the electron density on the metal. The vacant carbon monoxide pi antibonding orbitals are of similar size to the filled metal t 2g orbitals, thus the additional electron density on the metal (arising from the MoC bond) is donated from the metal t 2g orbitals back to carbon antibonding orbitals as shown below.

CSDS Teaching Modules • As the bonding is from the metal to the ligand rather than the usual ligand to metal, and because it involves pi orbitals, the phenomenon is termed pi back-bonding . This effect occurs in all metals however the effect is observer more commonly in metals with at least d4 electron configurations (fewer d electrons mean the metal has less electron density to donate back to the CO). We have used Mo in this example only to restrict the hitlist size. • But how does this affect the MoC and CO distances? • Donation of electrons from the CO to the Mo strengthens the MoC bond. But this effect increases the amount of electron density on the metal, which in turn means the metal has more electron density which it donates back to the CO. As the electron density involved in back- bonding is donated to the CO antibonding orbitals, this effectively lengthens the CO bond. • Return to ConQuest and look at refcodes DUSHAA and FOFTOK .

DUSHAA FOFTOK

MoC distance 1.887Å 2.012Å

CO distance 1.228Å 1.140Å

• These structures are at opposing ends of the scattergram and illustrate the effect described above.

7.5 ADVANCED EXCERCISES

7.5.1 What are the other resonance forms of CO? • Only one of the resonance forms of CO was used above to describe how CO bonds to a metal. There are another two resonance forms: can you draw them?

36 CSDS Teaching Modules 7.5.2 How could the phenomenon of pi backbonding be studied in the laboratory? • There is a simple analytical technique that can be used to monitor the CO bond strength. Hint: think of a technique that illustrates that a CO functional group is present in a structure... • CO stretching frequencies can be monitored using IR Spectroscopy. The stronger the CO bond, the higher the stretching frequency (cm -1 ).

7.5.3 Analyse other transition metal carbonyl complexes: does this effect occur for all metals? • This question is best answered by looking at the oxidation states for some of the complexes in our hitlist. What do you notice? • For the vast majority of complexes, the oxidation state is 0 e.g. BILMIS , OGAZAX . There are some complexes where the oxidation state is 2 e.g. FIRFUI , SONROC . The highest oxidation state is 4 ( CECZEP , CECZIT ). In short, all the complexes in our hitlist have fairly low oxidation states. • This is the case for metal carbonyls: for effective pi back bonding to occur there must be sufficient electron density on the metal. Metals in higher oxidation states will not have enough electron density to facilitate the back bonding.

7.6 SUMMARY OF KEY CONCEPTS • Searching the CSD for molybdenum carbonyl complexes and monitoring the MoC and CO bonds illustrates there is an effect whereby as the MC bond distance lengthens, the corresponding CO bond distance shortens (and vice versa). • The complementarity of this effect can be seen when the MoC distance is plotted against the CO distance in a statistical analysis package such as Vista: a linear relationship between the two distances is observed. • This phenomenon is called pi back-bonding and can be explained by electron donation between bonding and anti-bonding orbitals. • Pi back-bonding is found not only in MoCO complexes, but also other transition metal CO complexes. • The strength of pi back bonding in a metal carbonyl complex can be monitored using IR spectroscopy. • For optimal pi back bonding to occur, the metal must be in a low oxidation state.

CSDS Teaching Modules 38 CSDS Teaching Modules 8 DETERMINING MOLECULAR DIMENSIONS

8.1 INTRODUCTION • The accumulated data in the Cambridge Structural Database provides a wealth of structural information which, with rare exceptions, can be used to determine precise and unbiased estimates of molecular dimensions and conformational preferences. • When using experimentally determined results the ability to inspect and evaluate the underlying data is a key advantage and one that is not readily afforded by theoretical methods. In this module you will determine the preferred value of a Sb-Cl bond length and evaluate the precision of your findings using statistical criteria.

8.2 OBJECTIVES • To determine the preferred value of a Sb-Cl bond length in hexachloro-antimony by generating a bond length distribution from structures in the Cambridge Structural Database. • Evaluate the precision of the results you obtain using statistical criteria. • To examine the outliers in the Sb-Cl bond length distribution and attempt to distinguish those due to error from those that happen to be an interesting new discovery like a very short bond length.

8.3 GETTING STARTED • This module requires full access to the Cambridge Structural Database System. Specifically, the following software components will be used: • Mogul , a library of molecular geometry. • Mercury , for visualisation and examination of crystal structures. • The file bond_lengths.gcd is provided and contains the reference codes (refcodes) just those crystal structures which are specifically referred to in this tutorial.

8.4 STEPS REQUIRED

8.4.1 Background • The Cambridge Structural Database (CSD) is a primary source of experimental information on molecular geometries. For crystallographers and structural chemists, the main interest is often in bond lengths and angles. Comparison of the dimensions of a newly determined small- molecule crystal structure with the bond lengths and angles of similar structures in the CSD is useful as a check against refinement errors and to highlight unusual geometrical features. • Indeed, CSD-based printed compilations of the means, medians, and standard deviations of organic and organometallic bond lengths have been widely used to set up dictionaries for the restrained refinement of new crystal structures.

CSDS Teaching Modules • Mogul is a library of molecular geometry derived from the Cambridge Structural Database (CSD) and provides rapid access to the preferred values of bond lengths, valence angles and acyclic torsion angles. • Mogul is primarily used for structure validation, e.g. checking the molecular dimensions of new crystal structures, or validating the conformations of calculated, or modelled molecules. However, Mogul can also be used to very quickly look up the value of e.g. a particular bond length in a given query molecule.

8.4.2 What is the typical Sb-Cl bond length in hexachloro-antimony? • Start Mogul and hit the Draw button to open the Draw window. • Sketch hexachloro-antimony as shown below. In order to change the current element type to Sb click on the More... button, then select Other Elements... from the pull-down menu. Sb can then be selected from the Periodic Table.

• Hit Done to transfer the sketched structure to the Build query pane in the main Mogul window. • Select the two atoms that are needed to define one of the Sb-Cl bond lengths by clicking on them with the left-hand mouse button (if you make a mistake hit Reset to clear the current selection). Selected atoms will be highlighted within the query:

40 CSDS Teaching Modules • Hit Search to run the search. • Mogul will retrieve all crystal structures in the CSD that contain a Sb-Cl bond in the same chemical environment as the query molecule. The results are then presented as a histogram which shows the Sb-Cl bond length distribution calculated from those matching entries:

CSDS Teaching Modules • What is the average Sb-Cl bond length taken over all hit structures, i.e. what is the Mean of the bond length distribution? • How many Sb-Cl bond length fragments were found in the CSD, i.e. how many observations does the histogram contain? • A single crystal structure can, of course, contain more than one Sb-Cl bond length fragment e.g. a hexachloro-antimony ion will contain six. How many different crystal structures are represented in the histogram? You can view the CSD entries contributing to the histogram by clicking on the View structures tab. The refcodes of hit structures will appear in the list on the right-hand side, you can use the << and >> buttons to browse the hit structures.

8.4.3 Evaluating the precision of the data. • Return to the histogram by clicking on the Results and analysis tab. How confident are you that the Mean of the bond length distribution is an accurate estimate of a typical Sb-Cl bond length? In other words, since we are dealing with real data, might the results be influenced by experimental errors in individual observations? • The precision with which Mogul can predict molecular dimensions will be determined by the

42 CSDS Teaching Modules dispersion of the geometry distributions it produces. The reported Standard deviation of the distribution therefore serves as a measure of the precision of those measurements. A large Standard deviation would indicate that the data points are far from the mean and a small Standard deviation would indicate that they are clustered closely around the mean. • The Standard deviation of the Sb-Cl bond length distribution is reported under the Statistics listed on the left-hand side of the window. With a value around 0.06Å, the Standard deviation is higher than we would like. • The high Standard deviation is due to a number of severe outliers in the distribution i.e. CSD structures have unusually short or long Sb-Cl bond lengths. • What are the minimum and maximum Sb-Cl bonds lengths observed in the CSD? Are these observations valid, or could they be from structures that contain experimental errors?

8.4.4 Evaluate the outliers in the Sb-Cl bond length distribution. • In order to inspect just those CSD structures that contain unusually short Sb-Cl bond lengths: first deselect all hits in the histogram by clicking on the Deselect button, then highlight the two histogram bins located around 1.85Å using the horizontal bar located directly under the histogram:

• Click on the View structures tab to see the CSD entries that contribute to the selected bins. You will notice that all of the selected observations come from a single crystal structure: (CSD refcode: NARLEY ). • Use the Information , Diagram and 3D_Visualiser buttons on the left of the View structures tab to examine the structure. Can you account for the unusually short Sb-Cl bonds? • After an initial inspection the structure looks reasonable, further investigation is clearly

CSDS Teaching Modules needed. To view the original publication reporting the crystal structure, click on the Information button, then click on the Digital Object Identifier (DOI) hyperlink in the Literature Reference field. Note that a subscription to the publication in question will normally be required to view the on-line article. • The structure in question is referred to as 8b in the publication. Does the information given in the Results and Discussion section provide any clues to the reason for the unusually short Sb- Cl bond lengths? - - • The structure is reported as containing a SbF 6 counter-ion, not SbCl 6 . It is possible that the structure was incorrectly deposited with the database as the hexachloro-antimony ion, where, in fact, it should be a hexafluoro-antimony ion. Are the reported bond lengths of around 1.85Å more consistent with that expected for a Sb-F bond? Check this by running a Mogul search on SbF 6. Should this structure (CSD refcode: NARLEY ) be included in our Sb-Cl bond length analysis?

8.4.5 Evaluate the structure that contains the longest observed Sb-Cl bond length. • We have already determined that the shortest observed Sb-Cl bond lengths (~1.85Å) are in error. The hit structure containing these bond lengths is actually a hexafluoro-antimony ion. • Return to the Sb-Cl bond length distribution by selecting Searches from the top level menu, followed by Draw1: Sb1 Cl2 . • The longest Sb-Cl bond length is reported to be 3.1Å. Could this unusually long bond length also be due to error? • Examine the CSD structure that contains the long Sb-Cl bond (CSD refcode: CUMMON ). Use the Information , Diagram and 3D_Visualiser buttons on the left of the View structures tab to examine the structure in detail. 3- • Using the 3D_Visualiser you will see that the SbCl 6 anion has a strongly distorted octahedral geometry:

44 CSDS Teaching Modules • The structure contains three short (2.41 - 2.52Å) and three long (2.83 -3.11Å) Sb-Cl bonds. • The angles involving atoms which are mutually cis range from 81.73 (Cl6-Sb1-Cl5) to 97.97 (Cl4-Sb1-Cl5), while the trans angles are 174.47, 173.3 and 170.50, the last involving Cl3 and Cl6. The deviations of these bond angles from the ideal values of 90 and 180 are consistent with the presence of the long bonds, the largest deviations from 90 degrees involve the more weakly bonded chlorine atoms, Cl4-Sb1-Cl5 = 97.97, Cl5-Sb1-Cl6 = 81.7. • To investigate the reason for this strongly distorted octahedral geometry open Mercury and read in the file bond_lengths.gcd . Click on the refcode CUMNON in the Structure Navigator on the right hand side of the main Mercury window to view the structure. • Click on the tick box next to the words H-Bond Default definition in the list box underneath the 3D display. This finds all the hydrogen bonds formed by the two molecules that are currently displayed. Some of the hydrogen bonds are shown as broken red lines. Place the cursor anywhere on one of the broken red lines and left-click. This causes the complete molecule at the other end of the hydrogen bond to be shown. Repeat this process to build up a picture of the hydrogen bonding in this structure:

CSDS Teaching Modules • It is reasonable to conclude that the presence of multiple hydrogen bonds, mainly involving the three long-bonded chlorine atoms is responsible for the octahedral distortion. • Diethylenetriammonium hexachloroantimonate(III) (CSD refcode: CUMNON ) is an unusual and interesting structure. However, the reported Sb-Cl bond lengths are not in error.

8.5 SUMMARY OF KEY CONCEPTS • The CSD tries to report objectively what is presented in the literature. Therefore, in order to guarantee that the CCDC do not impose their idea of what is right or wrong but leave this judgement up to the crystallographers and the peer review process, suspicious crystal structures are not usually actively corrected without the authors consent. Inevitably this will mean that a small number of CSD entries will contain errors. • It is extremely important, for any scientist, to question the validity of any results or data they might obtain or be provided with. • When using experimentally determined results the ability to inspect and evaluate the underlying data is a key advantage and one that is not readily afforded by theoretical methods. • The accumulated crystal structure data in the CSD provides a wealth of structural information which, with rare exceptions, can be used to determine precise and unbiased estimates of molecular dimensions and conformational preferences.

46 CSDS Teaching Modules 9 ANALYSING 4-COORDINATE METAL GEOMETRY

9.1 INTRODUCTION • Conformation rearragements are well known in five coordinate species, involving interconversion between square pyramid and trigonal bipyramidal geometries. See R. R. Holmes, Acc. Chem. Res., 1979, 12, 257 and R. R. Holmes and J. A. Deiters, J. Am. Chem. Soc, 1977, 99, 3318 . • Four coordinate metals have a tendency to adopt one of two geometries: square planar or tetrahedral. However, these geometries can be affected by external factors, e.g. substituents, and thus not all metal complexes have idealised conformations. The geometries can be described using the four cis-ML 2 angles as well as the two trans-ML 2 angles. Clearly these would be expected to be around 90 o and 180 o respectively for square planar complexes while all angles would be around 109.5 o for tetrahedral complexes. • The 3D search facility available in ConQuest can be used to facilitate the study of such systems and potential interconversion ‘transition states’.

9.2 OBJECTIVES • Search for 4-coordinate transition metal complexes in the CSD and for each hit structure retrieve the values of the ML 2 angles (four ‘cis’ and two ‘trans’). • Determine the preferred geometries adopted by 4-coordinate transition metal complexes by analysing the collected geometric data. • Investigate some structures with non-idealised coordination geometries.

9.3 GETTING STARTED • This module requires full access to the Cambridge Structural Database System. Specifically, the following software components will be used: • ConQuest , for search and retrieval of crystal structure data. • Vista , for numerical analysis of ConQuest search results. • The file geometry_interconversion.gcd is provided and contains the reference codes (refcodes) just those crystal structures which are specifically referred to in this tutorial.

9.4 STEPS REQUIRED

9.4.1 Find 4-coordinate transition metal complexes in the CSD • Start ConQuest and hit the Draw button to open the Draw window. • Click on the More... button at the bottom of the Draw window and select Any Transition Metal from the resulting menu. Then click in the display area to draw the transition metal TR atom.

CSDS Teaching Modules • To specify that the transition metal must be uncharged right click on TR and select Charge followed by Zero from the resulting menus. This will produce a superscript 0ve on the right hand side of the TR . • To specify that the metal must have 4 bonded atoms (i.e. be 4 coordinate) right click on TR and select Number of Bonded Atoms , followed by 4 from the resulting menus. This will create a label T4 which should appear on the left hand side of TR .

• To specify that the transition metal can be bound to four ligands of any type click on the Bond button at the bottom of the Draw window and select Any from the resulting menu. Next, click on the atom type Any button at the bottom of the Draw window. Then, draw four Any atoms, which are represented by the letter X, and connect them to the metal with the bond type Any.

48 CSDS Teaching Modules • In this example we are only interested in monodentate ligands which are not connected or linked, therefore to specify that the X atoms must be acyclic click on Atoms in the main menu, then Cyclicity followed by Acyclic from the resulting menus. Select all four X atoms by clicking on them in the Draw window.

CSDS Teaching Modules • Once you have identified all of the acyclic atoms, click Done . • Next, to specify that the X atoms must have no direct cyclic links click on Bonds in the main menu and select Exclude . Click on the Direct Links tab, then once again select all of the ligand X atoms. Doing this means that none of the X atoms will be directly linked to one another. Once you have selected all of the X atoms, click on OK .

9.4.2 Run the search • Hit the Search button at the bottom right-hand corner of the drawing window. • A Search Setup window will pop up which allows you to specify which database you wish to search and also allows you to add filters to your search. For the purposes of this search, this will be left as it is. Hit Start Search at the bottom left of the screen to begin the search. • As soon as you start the search, the ConQuest interface moves to the View Results pane. After a few moments, the reference codes ( refcodes ) of hit structures will start to appear in the list on the right-hand side. How many hits are found? • Click on any structures refcode to see its chemical diagram, the transition metal substructure will be highlighted in red. Alternatively, use the << and >> buttons to scroll though some of the hits.

50 CSDS Teaching Modules Select 3D Visualiser from the tabs on the right hand side of the View results pane and inspect some of the hits. What metal coordination geometries are observed? • You should notice that the hits predominantly contain structures with square planar (e.g. AGLCUD and BDMIUP ) and tetrahedral (e.g. CETXOO and FOJBUB02 ) geometries.

left: square planar geometry in AGLCUD; right: tetrahedral geometry in CETXOO

9.4.3 Define geometric parameters • In order to analyse the 3D geometry of our 4-coordinate transition metal complexes we need to define some geometric parameters. The values of defined parameters can then be retrieved for each hit structure and analysed collectively.

• We will start by defining the angle between two unique ML 2 planes. Return to the Build Queries pane and click on Edit next to the query you just submitted. This should take you back to the Draw window. Click on the ADD 3D button on the left of the Draw window then select one of the X atoms, then the TR , then the next X atom, and finish by hitting the Define button next to Plane in the Geometric Parameters window.

CSDS Teaching Modules • Repeat with the remaining two ligand atoms and the transition metal to define the second plane in the same way. PLN1 and PLN2 should now have appeared in the Defined Objects box in the Geometric Parameters window. • Click on both PLN1 and PLN2 . This should allow you to define the angle between the two planes by clicking on the Define button next to Angle in the Geometric Parameters window.

52 CSDS Teaching Modules • We will now define the ML 2 angles: four ‘ cis ’ ones and two ‘ trans ’ ones. Click on one of the X atoms, then the TR , then the next X atom, similarly to the previous angle between the plane definition, except this time hit the Define button next to Angle .

CSDS Teaching Modules • Now click the Options... button underneath Angle and specify that the angle must lie between 0 and 150 o. This will restrict the ‘ cis ’ angles to less than 180 degrees, meaning that they must be ‘cis ’ angles, not ‘ trans ’.

54 CSDS Teaching Modules • Click OK to close the Limits and Options window. • Define the other three ‘ cis ’ angles in the same way. • Finally, define the two ‘ trans ’ angles with no angle constraints, then click on Done in the Geometric parameters window.

9.4.4 Run the search and export the data • Hit the Search button at the bottom right-hand corner of the drawing window (when prompted with the Overwrite query pop-up screen, select Yes - this will replace the initial query with the edited one). • Inspect some of the resultant hits. The angles you defined earlier should be given in the top right hand corner of the 2D visualiser. • Geometric parameters retrieved from a ConQuest search can be exported to Vista for analysis. Click on the Analyse Hitlist button in the View Results pane and select View in Vista , then in the resulting window click on the View in Vista button. The main Vista TABLE SPREADSHEET window should appear:

CSDS Teaching Modules • Vista displays the defined angles i.e. the angle between the planes, ANG1, and the TRX 2 angles, ANG2...ANG7 , for each entry in the database matching the substructure.

9.4.5 Analyse the geometric data

• Sum the TRX 2 angles by selecting Create... in the Parameters box on the left side of the Vista interface. This will generate a creating TRN10 window. Click on ANG2 , then the + button, then ANG3 etc. Once you have done this for all of the TRX 2 angles, i.e. summed all of the TRX 2 angles, press OK .

• This will create a new column in the table, labelled TRN10 . • To plot the summed angle data as a histogram select the parameter TRN10 by clicking on the grey numbered button at the top of the relevant column, then select Histogram from the Data Visualization options on the right hand side of the window.

56 CSDS Teaching Modules • Inspect the histogram, what does this tell you about the preferred geometries of 4-coordinate transition metal complexes? • Structures with tetrahedral geometries can be found around 660 degrees in the histogram (6 x 109.5 o) while the square planar structures are found close to 720 degrees (4 x 90 o plus 2 x 120 o). • Return to the spreadsheet window by clicking on RETURN .

• To plot a scattergram of the summed angles versus ANG1 (the angle between the two TRX 2 planes) click on the grey buttons above TRN10 and ANG1. This should highlight the appropriate columns. Then, select Scattergram , within the Data visualisation section on the right of the screen.

CSDS Teaching Modules • It is possible to link back to the original CSD entries by selecting data points in the scattergram then clicking on View Refcodes . What conclusions can you draw? • The scattergram shows that most four coordinate complexes are either square planar (in the top left of the scattergram) or tetrahedral (bottom right). However this is not always clear cut, exemplified by the fact that there are many database entries linking the two geometries resulting in a continuum. Closer inspection of the structures which are neither square planar nor tetrahedral represent the interconversion between the two geometries e.g. CCXAPT , COBZAU , CMTUCU10 .

9.5 SUMMARY OF KEY CONCEPTS

• Four coordinate metals (ML 4) predominantly adopt one of two geometries: square planar or tetrahedral. • In some complexes the energy difference between these two preferred geometries is small. Indeed, in a few specific complexes the difference in stability of the two possible stereochemical forms (square planar or tetrahedral) is so small that each can exist in the same crystal structure.

58 CSDS Teaching Modules • Dibromo-bis(benzyldiphenylphosphine) nickel(ii) (CSD refcode DBBZPN ) is one such structure. The term allogons (Greek: allos , other, different; andgonia , angle) is used to describe such isomers. This crystal is thus an interallogon compound.

Both square planar and tetrahedral forms exist together in dibromo-bis(benzyldiphenylphosphine) nickel(ii) (CSD refcode DBBZPN)

• The preferred square planar and tetrahedral geometries can be affected by e.g. the nature of the substituents, and thus not all metal complexes have idealised conformations. In fact there are many database entries linking the two idealised geometries resulting in a continuum. • The structures which are neither square planar nor tetrahedral can be regarded as snapshots of transition states along the interconversion pathway. i.e. proceeding along the continuum in the Vista distribution and viewing successive entries will allow the pathway for the interconversion between the square planar and tetrahedral geometries to be mapped out.

CSDS Teaching Modules 10 REACTION INTERMEDIATES: HALONIUM IONS

10.1 INTRODUCTION • Under certain circumstances reaction intermediates can be stable enough to be characterized by x-ray crystallography. The Cambridge Structural Database contains evidence of such species. • By examining the structure of intermediates we can gain insights into reaction mechanisms. In this module the mechanism for the electrophilic addition of halogens to an alkene will be explored using crystallographic data.

10.2 OBJECTIVES

• To evaluate possible mechanisms for the electrophilic addition of Br 2 to an alkene based on the stereochemistry of the products that are formed. • To search the Cambridge Structural Database for evidence of the existence of a cyclic bromonium ion intermediate. • To account for the observed stability of the adamantylidene-adamantane-bromonium ion.

10.3 GETTING STARTED • This module requires full access to the Cambridge Structural Database System. Specifically, the following software components will be used: • ConQuest , for search and retrieval of crystal structure data. • Mercury , for visualisation and examination of crystal structures. • The file halonium_ions.gcd is provided and contains the reference codes (refcodes) just those crystal structures which are specifically referred to in this tutorial.

10.4 STEPS REQUIRED

10.4.1 Electrophilic Addition of Br 2 to an Alkene

• A possible mechanism for the electrophilic addition of Br 2 to an alkene is outlined below.

60 CSDS Teaching Modules • As a bromine molecule approaches the nucleophilic alkene, the Br-Br bond becomes polarized. The electron pair from the double bond then attacks the polarized bromine forming a C-Br bond and displacing a bromide ion. The intermediate electrophilic carbocation then immediately reacts with the nucleophilic bromide ion to give the dibromo addition product. • Although this mechanism looks reasonable it is not consistent with the know facts. In particular, it does not explain the stereochemistry of halogen addition.

10.4.2 Investigate the stereochemistry of halogen addition • Lets look again at the addition reaction of bromine with cyclopentene. We will assume that Br + adds to cyclopentene from the bottom face to form the carbocation intermediate shown below:

• Since the positively charged sp 2 carbon is planar, it could be attacked by the bromide ion in the second step of the reaction from either the top or bottom face to give a mixture of products. One product has the two bromine atoms on the same side of the ring ( cis ), the other has the bromines on opposite sides ( trans ). • However, we actually find that only trans -1,2-dibromocyclopentene is produced. None of the cis product is formed. Therefore, the mechanism proposed above cannot be correct. • In order to explain the stereochemistry of halogen addition it has been suggested that the true reaction intermediate is not a carbocation, but is instead a bromonium ion. A bromonium ion is a symmetrical three-membered ring containing a bridged bromine atom carrying a positive charge. • If a bromonium ion is formed as an intermediate it would shield one face of the molecule. Attack by the bromide ion in the second step could then only occur from the opposite, unshielded face to give the trans product exclusively.

CSDS Teaching Modules • This mechanism would explain the observed stereochemistry of halogen addition reactions. However, can we find further evidence for the existence of the bromonium ion intermediate?

10.4.3 Search for evidence, in the Cambridge Structural Database, that the cyclic bromonium ion actually does exist. • Start ConQuest and hit the Draw button to open the Draw window. • Sketch the cyclic bromonium ion shown below. Remember to specify a charge of +1 on the bromine. This can be done, e.g. by right-clicking on the Br atom at selecting Charge , followed by Positive and then +1 from the resulting pull-down menus.

• Hit Search, then in the Search Setup window hit Start Search . • As soon as you start the search, the ConQuest interface moves to the View Results pane. After a few moments, the refcodes of any hit structures will appear in the list on the right-hand side. • You should retrieve two hits (refcodes DAKVUG and WEVPIW ). Both are examples of adamantylidene-adamantane-bromonium ions. Examine these two structures. • We can now confirm that bromonium ions are indeed real.

10.4.4 Find other examples of halonium ions • Search for other examples of halonium ions (F, Cl, I) in the Cambridge Structural database (CSD). • Write out the journal references for any halonium ions you find.

62 CSDS Teaching Modules • To write out a file containing the journal references click on File in the top-level menu and select Export Entries as... from the pull-down menu. Then click on the file type bar and select TXT: Text representation from the pull-down menu. Turn the output off for everything except Bibliographic information (using the check-boxes in the Select options section of the window). Hit Save to save the file of journal references. • When viewing CSD entries that which have a Digital Object Identifier (DOI) a clickable hyperlink to the original literature source will be available from the Author/Journal tab in the View Results pane. Articles are normally accessed via CrossRef ( http://www.crossref.org ) though links are also available where appropriate through the IUCr and LitLink. A subscription to the publication in question will normally be required to view the on-line article.

10.4.5 Explain the stability of the halonium ions found in the CSD. • Halonium ions are electrophiles and react immediately to form the addition product. However, the structures we have examined are clearly stable enough to be characterized by x- ray crystallography. What structural characteristics, possessed by all examples of halonium ions in the CSD, give rise to this special stability? • Open Mercury and read in the file halonium_ions.gcd . Browse the structures by clicking on each of the refcodes in the Structure Navigator on the right hand side of the main Mercury window. • You will notice that all examples of halonium ions in the CSD are produced by halogen addition to 2-(adamant-2-ylidene)adamantane (refcode ADYLAD01 ). This very hindered alkene forms halonium ions that are resistant to nucleophilic attack. • Examine closely the structure of adamantylidene-adamantane-bromonium tribromide (refcode DAKVUG ). The dihedral angle between the substituent planes of the carbons connecting the adamantyl rings is 32.76 degrees. This distortion from planarity results in close interatomic contacts between the H atoms on some of the carbons of the two adamantane groups. Consequently, there is severe steric crowding on the bottom face. The relevant distances are: 2.00 Å for H10 and H15 on C8 and C12, respectively; 2.01 Å, for H1, H24 on C2, C18; 2.14 Å for H9, H17 on C7, C13; and 2.15 Å for H13, H25 on C10, C19. • It is this severe crowding at the side opposite to the Br atom which prevents access of a nucleophile to the ion. This unusual feature is the likely source of the stability of the bromonium ion.

CSDS Teaching Modules Image showing the dihedral angle between the substituent planes of the carbons connecting the adamantyl rings in CSD refcode DAKVUG.

64 CSDS Teaching Modules Image showing severe crowding at the side opposite to the Br atom prevents access of a nucleophile to the ion

10.5 SUMMARY OF KEY CONCEPTS • The electrophilic addition of halogens to an alkene proceeds via a three-membered halonium ion intermediates to give the trans addition product.

• Halonium ions were first postulated in 1937 by Roberts and Kimball to account for the observed diastereoselectivity in halogenation of alkenes, see: The Halogenation of Ethylenes Irving Roberts, George E. Kimball J. Am. Chem. Soc .; 1937 ; 59(5); 947-948. The halonium ion postulate is a excellent example of deductive logic: from experimental results the mechanistic details of alkene electrophilic reactions were deduced.

CSDS Teaching Modules • Very hindered alkenes form halonium ions that are resistant to nucleophilic attack. Such ions are sufficiently stable to be characterized by x-ray crystallography. Thus, almost 50 years after haloniums ions were first proposed we have structural evidence that confirms their existence.

66 CSDS Teaching Modules 11 HAPTICITY

11.1 INTRODUCTION • The naming of organometallic compounds is similar to the naming of coordination compounds, but certain ligands can exhibit multiple modes of bonding, referred to as the hapticity. • Over half of the compounds in the Cambridge Structural Database are organometallic in nature, making the database an ideal resource for examining the bonding of such compounds.

11.2 OBJECTIVES • To investigate the concept of hapticity by analysing experimental crystal structure data. • To learn the nomenclature of hapticity by analysing experimental crystal structure data. • To examine the structural perturbations of ligands as a function of their hapticity.

11.3 GETTING STARTED • If you do not subscribe to the Cambridge Structural Database (CSD) System: • Open free Mercury (the free version of Mercury can be downloaded from http:// www.ccdc.cam.ac.uk/free_services/mercury/ ) • Open the free teaching subset of the CSD (downloadable from http://www.ccdc.cam.ac.uk/ free_services/teaching/downloads ) by selecting File from the top-level menu, followed by Open in the resulting menu, and then selecting the database file teaching_subset.ind • Database reference codes ( refcodes ) of the structures in the teaching database will appear in a list on the right hand side of the main Mercury window. To view a structure select the corresponding refcode in the list. • Once the teaching database has been loaded Mercury can then read text files containing lists of database reference codes ( refcodes ). To read in a file containing just those structures required for this tutorial hit File in the top-level menu, followed by Open , then select the file hapticity.gcd. • If you subscribe to the Cambridge Structural Database (CSD) System: • Open MercuryCSD. • The full database should be detected and opened within the Structure Navigator on the right hand side of the main Mercury window. • Once a database has been loaded Mercury can then read text files containing lists of database reference codes ( refcodes ). To read in a file containing just those structures required for this tutorial hit File in the top-level menu, followed by Open , then select the file hapticity.gcd. • Within the Structure Navigator loaded crystal structures are presented in a hierarchical tree organised first by file type ( Databases , Structures , Refcode Lists , ConQuest Hits , or Mercury Files ) and subsequently by filename and then by individual refcode . The file hapticity.gcd can be found under Refcode Lists . To view a structure select the corresponding refcode .

CSDS Teaching Modules 11.4 STEPS REQUIRED

11.4.1 Investigating metal-carbon bonding • Examine the structures of the first 4 entries in the file (these include csd refcodes: VADRAU , IGODIR , TODDUL , OKUSES ). • You will notice that each of these structures contains at least one metal-carbon bonding interaction. Each may be selected by clicking on the identifier (such as VADRAU ) from the Structure Navigator on the right hand side of the main Mercury window. Bonds between metal and carbon atoms are referred to as organometallic bonds. A ligand that contains a carbon atom which bonds to a metal is an organometallic ligand.

To manipulate structures in Mercury

1. Structures can be rotated by moving the cursor in the display area while keeping the left-hand mouse button pressed down.

2. To zoom in and out move the cursor up and down in the display area while keeping the right-hand mouse button pressed down.

4. At any stage the display area can be returned to the default view by hitting the Reset button at the bottom of the window.

• Change the display style from wireframe to spacefill. In spacefill, atoms are displayed as standard van der Waals radii. Generally when these radii overlap significantly, a bond between the two atoms is present. Mercury will automatically connect bonding atoms, based on a predetermined set of maximum bonding distances. Notice that in these five examples, each carbon atom bonded to a metal is from a separate ligand.

To change the display style:

Set the required style in the tool-bar Style box, located near the top of the main Mercury window. Al- ternatively, right-click in the display-area background, pick Styles from the pull-down menu, and select the required style (Wireframe, Capped sticks, Ball and stick, Spacefill, Ellipsoid).

• Inspect the structure of OKUSES closely. Which atoms are in van der Waals contact with the

68 CSDS Teaching Modules magnesium ion? Notice that the allyl ligand bonds to the magnesium ion with only one carbon atom. • Next, inspect the structure of ALPHPD01 closely. Again, identify which atoms are in van der Waals contact with the palladium ion. Notice that the allyl ligand has all three carbon atoms sufficiently close to the palladium ion to consider them all to be bonding to the palladium ion. • Clearly there is a difference in the way the allyl ligand is bonding to the different ions in the OKUSES and ALPHPD01 complexes. The nature of the bonding is not important to this exercise. All examples in this exercise utilize structural data from molecules which have been synthesized, crystallized and characterized by single crystal X-ray crystallography. • Now let's focus upon nomenclature. The number of contiguous ligand atoms bonding to a singular metal atom is defined as hapticity and is denoted using the Greek symbol η, eta, followed by a superscript indicating the number. The allyl ligand in OKUSES is attached to the metal by one carbon atom, so it is designated η1-allyl. The allyl ligand in ALPHPD01 is attached to the metal by three contiguous carbon atoms, so it is designated η3-allyl. • The allyl ligand may be described with the following Lewis structure.

• When the allyl ligand bonds to a metal with only one of its carbon atoms, the bonding is η1-allyl:

• The allyl anion may be represented by two resonance structures:

• The allyl anion has a delocalized pi system and may also be represented as follows:

CSDS Teaching Modules • A metal may interact with this delocatized pi system so as to have bonding interactions with all three allyl carbon atoms, that is the bonding is η3-allyl

• Closely examine the orientation of the η3-allyl ligand with respect to the metal in structure ALPHPD01 . Notice that the allyl carbon and hydrogen atoms are essentially coplanar; however, the metal does not reside in this plane. • With refcode ALPHPD01 selected in the Structure Navigator , click the More Info button followed by Structure Information from the resulting menu. Notice that the compound name is (η3-allyl)chlorotriphenylphosphinepalladium. The hapticity of the allyl ligand has been clearly denoted. While keeping the information window opened, select OKUSES in the Structure Navigator . Notice the compound name is cis-allylbromobis(dimethoxyethane)magnesium. In cases where the ligand binds η1 to the metal, the η1 binding mode is assumed and need not be noted. This is particularly true in cases where there is only one atom likely to bond to the metal. See for example the names for VADRAU and IGODIR . • WARNING: Although formally the lack of a hapticity notation implies the ligand bonds η1, very often chemists neglect to indicate hapticity, even when it is other than η1. Such omission often occurs when a ligand is bonding with its most commonly observed hapticity. Be sure to consider the chemistry when assigning hapticity to ambiguously named compounds.

11.4.2 Acyclic ligands • Examine the structures of the next 5 entries in the file (these include refcodes: KCEYPT , DUMVEM , BIPJEP , LAXLAY , DIJHIN01 ). • Identify the hapticity of the organometallic ligands and complete the table below. For diagrams, provide standard organic stick diagrams (Note: LAXLAY has two different organometallic ligands).

70 CSDS Teaching Modules CSD Refcode Compound Uncoordinated Hapticity Name Ligand

LAXLAY η1 (eta-1) (3,3,3- trifluoroethynyl phenylmercury(II)

LAXLAY

KCEYPT

BIPJEP

DIJHIN01

CSDS Teaching Modules CSD Refcode Compound Uncoordinated Hapticity Name Ligand

DUMVEM

• Notice that metal bonding fragment of all of the organometallic ligands in the above table are acyclic ligands.

11.4.3 Cyclic ligands • Examine the structure of Refcode entry FEROCE27 . • The metal bonding fragments of organometallic ligands are not restricted to being acyclic. In fact there are many (tens of thousands of examples in the Cambridge Structural Database alone†). The classic example is that of ferrocene which is comprised of two pentahapto - 5 cyclopentadienyl ligands bound to an iron(II) ion. That is, two C 5H5 ligands are bonding η to an iron ion, as depicted in the following diagram:

- • Like some of the above acyclic organometallic ligands, the atoms of the C 5H5 ligand are - essentially planar. The ferrocene iron ion is situated between two parallel C 5H5 ligands, halfway between the two rings and along the perpendicular connecting the ring centroids. These features are highlighted below, and are more clearly illustrated when you manipulate FEROCE27 in Mercury.

72 CSDS Teaching Modules Ferrocene (refcode FEROCE27) ring centroids are shown in blue

• Ferrocene is properly named bis( η5-cyclopentadienyl)iron(II) and may be represented by the 5 5 formula: ( η -C 5H5)2Fe. The cyclopentadienyl fragment is often abbreviated Cp, i.e. ( η - 5 Cp) 2Fe. The η coordination mode is so common for Cp that when hapticity is not noted, i.e. 5 Cp 2Fe, the η is assumed.‡ • Examine the structures of the next 6entries in the file. (These include refcodes: NOFPON , MULJIM , PEVHUT , FURROZ , ZOZLAB , TPCPCQ .) • Excluding any η1- ligands, identify the hapticity of the organometallic ligands and complete the table below. For diagrams, provide standard organic stick diagrams.

CSD Refcode Compound Uncoordinated Hapticity Name Ligand

η3 (eta-3)

η4 (eta-4)

CSDS Teaching Modules CSD Refcode Compound Uncoordinated Hapticity Name Ligand

MULJIM η5 (eta-5) carbonyl ( η5- cyclopentadienyl) diiodocolbalt (III)

η6 (eta-6)

η7 (eta-7)

η8 (eta-8)

† Over 40,000 structures containing η2- or greater hapticity carbon atom rings ranging in size from three to eight carbon atoms were in the CSD (database version 5.28, 2007 release).

‡ Over 15,000 η5--Cp containing structures were in the CSD (database version 5.28, 2007 release).

11.4.4 Variable hapticity • Many organometallic ligands are capable of variable hapticity. Earlier we saw that the allyl ligand can bond either η1 or η3 to a metal. In cis-allylbromobis(dimethoxyethane)magnesium, sterics dictate that the allyl ligand bonds η1 to the magnesium ion (see OKUSES ). In contrast, there is sufficient space in η3-allylchloro(triphenylphosphine)palladium(II) for the allyl ligand to bond η3 to the palladium ion (see ALPHPD01 ). It is even possible to isolate compounds where the same type of ligand bonds with variable hapticity to the same metal. A fine example is the compound ( η3-allyl)bis( η1-allyl)(1,2-bis(diphenylphosphino)benzene)iridium(III) (see WIZKEV ). - - • The cyclopentadienyl ligand, C 5H5 , or Cp is also versatile in it’s bonding modes, examples include CSD refcodes CACWOS , PEJGAM , and MULJIM . For each of these structures identify

74 CSDS Teaching Modules the mode of bonding of the Cp - ligand.

11.4.5 Heteroatoms in rings • Examine the structure of Refcode entry EBEDUK . • To this point, all the examples illustrated have only used hapticity to describe metal to carbon bonding; however, the use of hapticity terminology may be used to describe the bonding of any organic moiety to a metal. For example, bis( η5-2,3,4,5-tetramethylpyrrolyl)ruthenium(II). That 5 is, two C 4Me 4N- ligands are bonding η to a ruthenium ion, as depicted in the following diagram:

• In the case of (C 4Me 4N) 2Ru, all ring carbon atoms AND the nitrogen heteroatoms are bonding to the metal, so the η5 designation is appropriate. A heteroatom in a ring need not necessarily bond to the metal, in which case it would not be included in the hapticity count. For example, the compound C 13 H11 FeNO 6 below has tetrahapto coordination to four carbon atoms; however, the nitrogen in the ring does not bond to the metal.

CSDS Teaching Modules • A good name for the this compound is 4,5,6,7- η4-(3-formyl-N- ethoxycarbonylazepine)tricarbonyl iron(0). The "4,5,6,7"preceding the " η4" is necessary to explicitly distinguish between this compound and other isomers such as the 2,3,4,5- η4 isomer. Sketch the 2,3,4,5- η4 isomer.

11.5 SUMMARY OF KEY CONCEPTS • Often a ligand with carbon donor atoms can exhibit multiple bonding modes. For example, we have seen that the cyclopentadienyl ligand can bond to d-metal atoms in three different ways. Thus we need additional nomenclature to describe these different modes of bonding. • Use of the Greek prefix η (eta) accompanied by a superscript number (e.g. η4) describes the number of atoms in a ligand that are considered formally to be bonded to the metal atom. This is the hapticity of the ligand. • For example, ( η3-Allyl)-( η4-butadiene)-( η5-cyclopentadienyl)-molybdenum(ii) (CSD refocde RATQUY ), shown below.

• In 1968, F. A. Cotton proposed the hapticity nomenclature in a letter to the Journal of the American Chemical Society. (Cotton, F. A. J. Am. Chem. Soc . 1968 , 90( 22 ), 6230-6232: http:// dx.doi.org/10.1021/ja01024a059 .) The notation he proposed remains the standard today. • Cotton illustrates the notation using 16 examples. If you have full access to the Cambridge Structural Database (CSD) then, as an additional exercise, use ConQuest to find structure entries which match the 16 examples. Which of the 16 have CSD entries which exactly match the structures as depicted by Cotton? Which, if any have matching formulas, but are structurally different than depicted by Cotton? For those examples that lack exact formula matches, find the CSD entries which are most similar. In each case, give the name, according to Cotton's nomenclature, that correctly describes each molecule.

76 CSDS Teaching Modules 12 CONFORMATIONS OF RINGS

12.1 INTRODUCTION • In 1885 Adolf von Baeyer proposed that if carbon prefers to have a tetrahedral geometry with bond angles of 109.5 degrees, then ring sizes other than 5 and 6 may be too strained to exist. The basis for this proposal was that all ring system are planar, clearly this is not the case. Ring systems can adopt many different conformations just a easily as acyclic compounds do. • The Cambridge Structural Database is a unique resource providing a wealth of information on the preferred conformations of rings. Indeed, the database has been used extensively to map the conformational space of medium ring-sized cyclic and heterocyclic compounds ( Acta Cryst ., B49 , 910, 1993) and of macrocyclic ether and thioether ligands ( Acta Cryst ., B 53 , 241, 1997). • By examining crystal structures we can and understand why the observed conformations are adopted in terms of the strain present in these systems

12.2 OBJECTIVES • To investigate and understand the reason for angle strain in fully saturated planar carbocyclic rings. • For cyclohexane, determine the angle strain in actual compounds by analysing experimental crystal structure data. • To compare the predicted angle strain (in planar rings) against that observed in actual compounds and account for the differences. • To closely examine the conformations of 3- to 6-membered carbocyclic rings and understand why these conformations are adopted in terms of the strain present in these systems.

12.3 GETTING STARTED • If you do not subscribe to the Cambridge Structural Database (CSD) System: • Open free Mercury (the free version of Mercury can be downloaded from http:// www.ccdc.cam.ac.uk/free_services/mercury/ ) • Open the free teaching subset of the CSD (downloadable from http://www.ccdc.cam.ac.uk/ free_services/teaching/downloads ) by selecting File from the top-level menu, followed by Open in the resulting menu, and then selecting the database file teaching_subset.ind • Database reference codes ( refcodes ) of the structures in the teaching database will appear in a list on the right hand side of the main Mercury window. To view a structure select the corresponding refcode in the list. • Once the teaching database has been loaded Mercury can then read text files containing lists of database reference codes ( refcodes ). To read in a file containing just those structures required for this tutorial hit File in the top-level menu, followed by Open , then select the file ring_conformations.gcd.

CSDS Teaching Modules • If you subscribe to the Cambridge Structural Database (CSD) System: • Open MercuryCSD. • The full database should be detected and opened within the Structure Navigator on the right hand side of the main Mercury window. • Once a database has been loaded Mercury can then read text files containing lists of database reference codes ( refcodes ). To read in a file containing just those structures required for this tutorial hit File in the top-level menu, followed by Open , then select the file ring_conformations.gcd. • Within the Structure Navigator loaded crystal structures are presented in a hierarchical tree organised first by file type ( Databases , Structures , Refcode Lists , ConQuest Hits , or Mercury Files ) and subsequently by filename and then by individual refcode . The file ring_conformations.gcd can be found under Refcode Lists . To view a structure select the corresponding refcode .

12.4 STEPS REQUIRED

12.4.1 Investigate angle strain in planar rings. • Ideally the sp 3 hybridised carbon atoms of fully saturated carbocyclic rings would adopt bond angles of 109.5 degrees. However, in planar rings the internal bond angles will depend on the number of atoms in the ring.

• The table below gives values for the internal angles for the regular planar polygons shown above and an indication of angle strain per carbon atom due to deviation from the ideal sp 3 angle of 109.5 degrees.

No. atoms Internal angle in planar Measure of angle strain in ring ring (degrees) abs(internal angle - 109.5) 3 60 49.5 4 90 19.5 5 108 1.5 6 120

78 CSDS Teaching Modules No. atoms Internal angle in planar Measure of angle strain in ring ring (degrees) abs(internal angle - 109.5) 7 128.5 8 135

• Complete the table above by calculating the angle strain (angle stain = internal angle - 109.5) for 6- to 8-membered rings. • This data is best presented as a graph. Plot the predicted angle strain against ring size (for three- to eight-membered planar rings). What conclusions can you draw? • Strain is predicted to be largest for three-membered rings but rapidly decreases and reaches a minimum for a five-membered ring. In fact, a planar five-membered ring is predicted to be virtually free of angle strain. After the minimum at five, angle strain increases steadily as the rings get larger.

12.4.2 Calculating angle strain in actual compounds • So far we only have a predicted value of angle strain in planar rings. We need a measure of angle strain in actual compounds, so that we can compare this to the predicted values. • The preferred angle in actual compounds can be determined, for an n-membered carbocyclic ring, by taking the average internal angle across a large number crystal structures. Angle strain can then be calculated as the difference between this average internal angle and the ideal sp 3 angle of 109.5. • Calculate, from crystal structure data, the actual angle strain in cyclohexane. For this task you are provided with 5 structures each containing a cyclohexane ring (CSD refcodes: ALIPIU , AZANUK , CYCHEX , CHXDCA and BCYHAC ). To view a structure click on its refcode in the Structure Navigator on the right hand side of the main Mercury window. For each structure measure all six internal C-C-C angles, then calculate the average internal angle of each structure and the overall average across the whole set.

To measure angles in Mercury

1. Set Picking Mode in the tool bar (near the top of the main Mercury window) to the required parameter type, viz. Measure Distance , Measure Angle or Measure Torsion

2. Geometrical measurements (intramolecular or intermolecular) can now be made by clicking on e.g., two atoms for a distance, three atoms for an angle or four atoms for a torsion angle.

3. To remove all geometrical measurements from the display click on the Clear Measurements button in the tool bar near the top of the main Mercury window.

CSDS Teaching Modules • Note: For the purpose of this task only a small number of representative structures are provided. However, if you have full access to the Cambridge Structural Database (CSD) the average internal angle can be calculated across a large number of cyclohexane fragments (see SUPPLEMENTARY MATERIAL: DETERMINING THE PREFERRED INTERNAL BOND ANGLE IN CYCLOHEXANE USING THE FULL CSD, page 85).

12.4.3 Compare predicted angle strain against that calculated from actual compounds • The table below shows both the predicted angle strain (in planar rings) and the angle strain calculated from actual compounds. • Complete the table by entering the angle strain in cyclohexane calculated from actual compounds. Angle strain = average internal angle across all 5 structures - 109.5.

No. Atoms Measure of Angle Strain in Ring (internal angle - 109.5) Predicted Calculated (in planar rings) (crystal structure data) 3 49.5 49.5 4 19.5 21 5 1.5 6 6 10.5 7 19 6.5 8 25.5 7

• Add the angle strain data calculated from actual compounds to the graph we plotted previously. This will allow us to easily compare the predicted angle strain against that observed in actual compounds.

80 CSDS Teaching Modules Plot comparing predicted angle strain in planar rings against that calculated from actual compounds

• Compare the two data series. What conclusions can we draw? • The observed angle strain is greatest in cyclopropane. Angle strain then decrease rapidly with ring size but reaches a minimum for cyclohexane, not cyclopentane (as predicted for the planar structure). Angle strain then increases again but not nearly as quickly as predicted. • Why are six-membered rings essentially free of angle strain? and why is there some angle strain in five membered rings even though the bond angles in the planar structure are almost 109.5 degrees? • The answer, at least to the first question, is that rings in actual compounds are not planar, they can adopt many different conformations just a easily as acyclic compounds do. To help answer the second question, lets look at some ring conformations in more detail.

12.4.4 Examine the conformation of cyclopropane • Display the structure of cyclopropane by clicking on the refcode QQQCIS01 from the Structure Navigator on the right hand side of the main Mercury window. • Examine the structure. The three carbon atoms of cyclopropane lie in a plane. Three membered rings must be planar since it is always possible to draw a plane through any three points.

CSDS Teaching Modules • We know already that there is considerable angle strain in this planar molecule. This is due to the bond angles deviating from the ideal tetrahedral value of 109.5 degrees. However, there is a further cause of strain in cyclopropane. Can you identify what this is? ( hint : it may help to view along one of the C-C bonds).

To view along bonds in Mercury

1. The view direction in Mercury can be changed so that you are looking down a particular bond.

2. To view along a bond, right-click on the bond and select View along bond from the resulting pull- down menu.

3. At any stage the display area can be returned to the default view by hitting the Reset button at the bottom of the window

• All the C-H bonds in cyclopropane are eclipsed. This is energetically unfavourable and any rotation would lead to a more stable conformation. however, C-C bond rotation is impossible and so all the C-H bonds are forced to eclipse their neighbours. The strain resulting from eclipsed conformations is called Pitzer strain.

12.4.5 Examine the conformation of cyclobutane • Display the structure of octachlorocyclobutane by clicking on the refcode CLCBUT from the Structure Navigator on the right hand side of the main Mercury window. • Examine the structure. In octachlorocyclobutane the ring distorts from a planar conformation in order to reduce the eclipsing interactions, even though this increases the angle strain. Octachlorocyclobutane therefore adopts a wing-shaped conformation, with an angle between the planes of about 26 degrees. • View along one of the C-C bonds in order to see how this deviation from planarity relieves the C-Cl eclipsing interactions.

82 CSDS Teaching Modules left: wing-shaped conformation of octachlorobutane (CLCBUT) showing angle between planes; right: this wing-shaped conformation relieves the C-Cl eclipsing interactions.

• By comparison, oxetane ( CIVXIO10), in which eclipsing is less, is closer to planarity. Measure the distance between the two C-C-C planes in oxetane.

12.4.6 Examine the conformation of cyclopentane • This eclipsing effect explains why is there some angle strain in five membered rings even though the bond angles in the planar structure are almost 109.5 degrees. • We now know that in the planar molecule there would be considerable strain caused by eclipsing of adjacent C-H bonds. Therefore the ring distorts (as in cyclobutane) to reduce these eclipsing interactions, but this increases the angle strain. Whatever happens there will always be some strain present. The minimum energy conformation adopted is therefore a balance of the two opposing types of strain. • There are two puckered conformations of cyclopentane, the envelope (IHIPOE, ACUHUB) and the half-chair (LISLOO, ABIKUR) . There is little energy difference between the two forms and many five-membered ring systems adopt conformations somewhere between the two.

CSDS Teaching Modules conformations of cyclopentane, left: envelope (IHIPOE); right: half-chair (LISLOO)

12.4.7 Examine the conformation of cyclohexane • Display the structure of cyclohexane by clicking on the refcode CYCHEX from the Structure Navigator on the right hand side of the main Mercury window. • From our analysis of crystal structure data we have determined that six-membered rings are essentially free of angle strain. Inspect the structure of cyclohexane and explain why this is. • Cyclohexane adopts a puckered conformation that relieves all strain. This conformation is called the chair . • In the chair conformation of cyclohexane all bond angles are close to the ideal tetrahedral angle of 109.5 degrees. In addition, viewing along any of the C-C bonds clearly shows that there are no eclipsing C-H interactions. All bonds are fully staggered, i.e. in a gauche arrangement, giving the lowest possible energy. This is why cyclohexane is essentially strain-free. • In the vast majority of compounds containing a cyclohexane ring, the molecule exist almost entirely in the chair form. However, other cyclohexane conformations are know. These conformations and substituted cyclohexanes are dealt in detail elsewhere ( CSD teaching module #n ).

84 CSDS Teaching Modules Chair conformation of cyclohexane (CYCHEX)

12.5 SUMMARY OF KEY CONCEPTS • Angle strain can occur in cycloalkanes due to deviation from the ideal sp 3 angle of 109.5 degrees. • Strain can also occur when neighboring bonds are forced to be eclipsed, or partially eclipsed. The strain resulting from eclipsed conformations is called Pitzer (or torsional ) strain. • Cyclopropanes are forced to be planar and are highly strained because of both angle strain and the eclipsing of C-H bonds. • Cyclobutanes adopt a wing-shaped conformation. This deviation from planarity occurs in order to relieve the eclipsing of neighboring bonds. • Cyclopentanes are not planar even though the bond angles in the planar structure would be almost 109.5 degrees. Again, this distortion occurs in order to relieve eclipsing of adjacent C-H bonds. The minimum energy conformation adopted is therefore a balance between the two opposing types of strain. • Cyclohexane is strain free because of its puckered chair conformation, in which all bond angles are close to 109.5 degrees and all neighboring C-H bonds are staggered. Cyclohexane rings are the most important of all ring sizes because of there wide occurrence. As such, cyclohexanes are dealt with in detail elsewhere ( CSD teaching module #n ).

12.6 SUPPLEMENTARY MATERIAL: DETERMINING THE PREFERRED INTERNAL BOND ANGLE IN CYCLOHEXANE USING THE FULL CSD

• Start ConQuest and hit the Draw button to open the Draw window.

CSDS Teaching Modules • Draw a cyclohexane substructure ( hint : this can be done quickly by selecting the appropriate ring template from the bottom left-hand corner of the Draw window and then clicking in the white drawing area). Since we also want to retrieve substituted cyclohexanes don’t include any hydrogen atoms when sketching your search substructure. • For each hit structure retrieved by the search we need to record the average of the six internal bond angles in the cyclohexane fragment. To define the required geometric parameters click on the Add 3D button. This will open the Geometric Parameters window. Click on the All Parameters... button, then in the resultant dialogue box select Define all: Valence Angles from the drop down menu. Choose to tabulate the average of these angles by enabling the tick-box next to the word Average .

• Hit OK , to define the selected parameters and then Done to close the Geometric Parameters window. • Hit Search, then in the Search Setup window set the filters R factor <= 0.1 , Not disordered and No errors , and then hit Start Search . • As soon as you start the search, the ConQuest interface moves to the View Results pane. After a few moments, the refcodes of hit structures will start to appear in the list on the right-hand side. Click on any structures refcode to see its chemical diagram, the cyclohexane substructure will be highlighted and the average value of the internal valence angles will also be displayed. • The blue progress bar indicates how much of the CSD has been searched so far. There is no need to allow the search to go to completion, you can stop it after about 20% by hitting the Stop

86 CSDS Teaching Modules Search button in the bottom right-hand corner. • Geometric parameters retrieved from a ConQuest search can be exported to Vista for statistical analysis. Select File from the top-level menu followed by View in Vista..., then in the resulting window click on the View in Vista button. The main Vista TABLE SPREADSHEET window should appear:

• To determine the mean value of the average internal angle across all hit structures select the parameter AVG1 by clicking on the grey numbered button at the top of the relevant column, then select Histogram from the Data Visualization options on the right hand side of the window. • The resulting histogram shows the distribution of the average internal cyclohexane valence angle across a large number of crystal structures.

CSDS Teaching Modules • The mean value is given on the right hand side of the plot. Calculate the angle strain by subtracting this value from 109.5 (the ideal sp 3 angle). The angle strain should be close to zero.

88 CSDS Teaching Modules 13 STEREOCHEMISTRY

13.1 INTRODUCTION • Stereoisomers are molecules whose atomic connectivity is the same but whose three- dimensional arrangement of atoms in space is different. • This has sweeping implications in biological systems. For example, most drugs are often composed of a single stereoisomer of a compound, and while one stereoisomer may have positive effects on the body (since it has the right three-dimensional shape to bind to the protein receptor), another stereoisomer may not bind, or could even be toxic. An example of this is the drug thalidomide which was used during the 1950s to suppress morning sickness. The drug, unfortunately, was prescribed as a mixture of stereoisomers, and while one stereoisomer actively worked on controlling morning sickness, the other stereoisomer caused serious birth defects. Ultimately the drug was pulled from the marketplace. • Because of these implications, a great deal of work done by synthetic organic chemists is in devising methods to synthesize compounds that are purely one stereoisomer. • The ability to visualise and manipulate molecules in three-dimensions is vitally important in order to study and understand the structural features that give rise to stereoisomerism.

13.2 OBJECTIVES • Recognise a stereogenic (chiral) centre in a molecular structure. • Use the sequence rules for specification of configuration to identify and name correctly stereoisomers and individual stereogenic (chiral) centres having R or S absolute configurations. • To be able to predict, identify and distinguish between enantiomers and diastereoisomers. • To recognise a meso compound given its structure. • To be able to recognise other structural features that can give rise to chirality, including quadrivalent chiral atoms, tervalent chiral atoms, restricted rotation, and helical shape.

13.3 GETTING STARTED • If you do not subscribe to the Cambridge Structural Database (CSD) System: • Open free Mercury (the free version of Mercury can be downloaded from http:// www.ccdc.cam.ac.uk/free_services/mercury/ ) • Open the free teaching subset of the CSD (downloadable from http://www.ccdc.cam.ac.uk/ free_services/teaching/downloads ) by selecting File from the top-level menu, followed by Open in the resulting menu, and then selecting the database file teaching_subset.ind • Database reference codes ( refcodes ) of the structures in the teaching database will appear in a list on the right hand side of the main Mercury window. To view a structure select the corresponding refcode in the list. • Once the teaching database has been loaded Mercury can then read text files containing lists

CSDS Teaching Modules of database reference codes ( refcodes ). To read in a file containing just those structures required for this tutorial hit File in the top-level menu, followed by Open , then select the file stereochemistry.gcd. • If you subscribe to the Cambridge Structural Database (CSD) System: • Open MercuryCSD. • The full database should be detected and opened within the Structure Navigator on the right hand side of the main Mercury window. • Once a database has been loaded Mercury can then read text files containing lists of database reference codes ( refcodes ). To read in a file containing just those structures required for this tutorial hit File in the top-level menu, followed by Open , then select the file stereochemistry.gcd. • Within the Structure Navigator loaded crystal structures are presented in a hierarchical tree organised first by file type ( Databases , Structures , Refcode Lists , ConQuest Hits , or Mercury Files ) and subsequently by filename and then by individual refcode . The file stereochemistry.gcd can be found under Refcode Lists . To view a structure select the corresponding refcode .

13.4 STEPS REQUIRED

13.4.1 Investigate the structure of the amino acid alanine. • Examine and compare two crystal structures of alanine (CSD refcodes ALUCAL04 and ALUCAL05 ). A structure can be display by selecting its refcode from the Structure Navigator on the right hand side of the main Mercury window. What is the relationship between these two structures, are they identical?

90 CSDS Teaching Modules To manipulate structures in Mercury

1. Structures can be rotated by moving the cursor in the display area while keeping the left-hand mouse button pressed down.

2. To zoom in and out move the cursor up and down in the display area while keeping the right-hand mouse button pressed down.

4. At any stage the display area can be returned to the default view by hitting the Reset button at the bottom of the window.

• Although the two structures initially look identical, after careful inspection, we can see they are not the same. The structures are non-superimposable. However we orientate the structures we cannot directly overlay one onto the other such that all four substituents align. Note that if you have full access to the Cambridge Structural Database then you will be able to display both structures together and manipulate them independently. Try to overlay one structure onto the other. However the structures are orientated all four substituents cannot be aligned. • In fact, the two structures are mirror-images of each other. If we reflected ALUCAL04 in a mirror, we would get a structure that is identical to ALUCAL05 .

• Two structures that are not identical, but are mirror images of each other are called enantiomers. Structures that are not superimposable on their mirror image and can therefore exist as two enantiomers are called chiral. • Enantiomers are identical in all physical properties except for the direction in which they rotate the plane of polarised light. Compounds that are able to rotate the plane of polarized light are said to be optically active.

CSDS Teaching Modules 13.4.2 Identifying chirality. • How can we predict whether or not a molecule is chiral? • A molecule can’t be chiral if it contains a plane of symmetry. If a molecule has a plane of symmetry then it will be superimposable on its mirror image and will be achiral. • Any molecule containing a carbon atom carrying four different groups will not have a plane of symmetry and must therefore be chiral. Such carbon atoms are know as stereogenic or chiral centers. • All amino acids have a carbon carrying an amino group, a carboxyl group, a hydrogen atom and an R group (for alanine R=methyl). Therefore, all amino acids (except for glycine where R=H, see CSD refcode GLYCIN ) are chiral. • Natural alanine, extracted from plants, consists of one enantiomer only. Samples of chiral molecules that contain only one enantiomer are called enantiomerically pure. However, alanine produced in the lab from achiral starting materials will be a 50:50 mixture of enantiomers and is referred to as being racemic. In fact, nearly all chiral molecules in living systems are found as single enantiomers not as racemic mixtures. • Examine each of the following structures and determine whether or not they are chiral. • Toluene (CSD refcode: TOLUEN ) • Lactic acid (CSD refcode: YILLAG ) • Citric acid (CSD refcode: CITARC ) • 2,2,2-Trifluoro-1-(9-anthryl)ethanol (CSD refcode: SOCLIF )

13.4.3 Describing the configuration of a chiral centre. • How do chemists explain which enantiomer they are talking about? One way is to use a set of rules to assign a letter R or S , to describe the configuration of groups at a chiral centre. • Display the structure of alanine (CSD refcode: ALUCAL04 ) by selecting it from the Structure Navigator on the right hand side of the main Mercury window. • First, look at the four atoms directly attached to the stereogenic centre and assign priorities in order of decreasing atomic number. The group with the highest atomic number is ranked first, the lowest atomic number is ranked fourth. If two or more of the atoms are identical, then we assign priorities by assessing the atoms attached to those atoms, continuing on as necessary until a difference is found.

• So, we assign priority 1 to the NH 3 group. Priorities 2 and 3 will be assigned to the CO 2 and CH 3 groups respectively since the CO 2 group carries oxygen atoms whereas the CH 3 only carries hydrogen atoms. Finally, priority 4 is assigned to the hydrogen atom. • Now, orientate the molecule in the display so that the lowest priority substituent (the hydrogen) is pointed away from you. The hydrogen should be almost eclipsed by the chiral carbon atom.

• Next, mentally trace a path from substituent priority 1 (NH 3) to 2 (CO 2) to 3 (CH 3). If we are

92 CSDS Teaching Modules moving in a clockwise direction, then we assign the label R to the chiral centre; if we move in an anticlockwise direction, we assign the label S.

• What is the configuration of our alanine molecule? Is it the ( S)-alanine, or ( R)-alanine enantiomer? • Some further examples of chiral molecules are provided. Identify the chiral centre in each of the following molecules and assign their configuration using R and S notation: • Carvone (spearmint oil) (CSD refcode: RERXIV ) • Adrenaline (CSD refcode: ADRENL ) • Ibuprofen (CSD refcode: JEKNOC10 ).

13.4.4 Compounds containing more than one stereogenic center. • Alanine is relatively simple to deal with, it contains only one chiral center and can therefore only exist in two enantiomeric forms. • Now, examine the structure of threonine (2-amino-3-hydroxybutanoic acid) (CSD refcode: LTHREO01 ). You will see that threonine has two stereogenic centers (on C2 and C3). Assign R and S configuration to each stereogenic center. • You should find that LTHREO01 has a (2S,3R) configuration. This can be drawn in 2D as shown below:

CSDS Teaching Modules • What other stereoisomers could exist for threonine? Draw all possible stereoisomers, identifying the configuration at each chiral center. What is the relationship between these stereoisomers? • There are four stereoisomers of threonine. These can be classified into two mirror image pairs of enantiomers. The 2R,3R stereoisomer is the mirror image of 2S,3S, and the 2R,3S stereoisomer is the mirror image of 2S,3R. But what is the relationship between any two configurations that are not mirror images (e.g. between 2R,3R and 2R,3S)? • Stereoisomers that are not mirror images are called diastereoisomers. Note the difference between enantiomers and diastereoisomers: enantiomers must have opposite (mirror image) configurations at all stereogenic centers; diastereoisomers must have opposite configurations at some stereogenic centers, but the same configuration at others. These relationships are summarised below:

94 CSDS Teaching Modules • Lets look at another example. Ephedrine (CSD refcode: EPHEDR01 ) and pseudoephedrine (CSD refcode: PSEPED01 ) each contain two stereogenic centers and are stereoisomers. Ephedrine is used in nasal sprays as a decongestant and pseudoephedrine is the active component of the decongestant Sudafed. • Examine these two structures in detail, identify the two chiral centres in each molecule and assign their configuration using R and S notation. Describe the relationship between these two stereoisomers.

13.4.5 Compounds that contain stereogenic centers but are achiral. • Tartaric acid, like threonine, contains two stereogenic centers so again we might expect four stereoisomers: two diastereoisomers, each existing as a pair of enantiomers:

CSDS Teaching Modules • However, we actually find there are only three stereoisomers of tartaric acid (CSD refcodes: TARTAC , TARTAL04 and TARTAM ). Can you determine why this is? Examine all three structures closely. For each structure, assign the configuration at both stereogenic centers and match the structure with the corresponding stereoisomer in the diagram above. • You should find that TARTAM can be matched against both the R,S and S,R configurations shown in the diagram above. R,S -Tartaric acid and S,R -tartaric acid are identical, this can be seen by rotating one structure 180 degrees. The identity of the R,S and S,R structures results from the fact that the molecule has a plane of symmetry. This plane cuts through the C2-C3 bond, making one half of the molecule a mirror image of the other. • Compounds that contain stereogenic centers but are achiral (due to a symmetry plane) are called meso compounds. Tartaric acid therefore exists as three stereoisomers: two enantiomers (CSD refcodes: TARTAC and TARTAL04 ) and one achiral meso form (CSD refcode: TARTAM ).

13.5 ADVANCED EXCERCISE

• So far we have only considered compounds containing chiral carbon atoms. However, other kinds of molecules can also display chirality. In the following sections, we will look at some examples of these.

13.5.1 Compounds with quadrivalent chiral atoms other than carbon. • Any molecule containing an atom that has four bonds orientated towards the corners of a tetrahedron will be optically active if the four groups are different. For an example of a compound with a quadrivalent chiral Si atom see CSD refcodes: YONMET and YONMIX .

96 CSDS Teaching Modules • Examine each of these two stereoisomers in turn by clicking on their refcodes in the Structure Navigator on the right hand side of the main Mercury window. Assign R or S configuration to the Si atom in each structure.

13.5.2 Substituted adamantanes. • Molecules that resemble an expanded tetrahedron will have the same symmetry properties as a regular tetrahedral atom and can therefore be chiral. For example, adamantanes containing four different substituents at the bridgehead positions are chiral and optically active. • Display the structure of 1-bromo-3-chloro-5-fluoro-7-iodoadamantane by clicking on the refcode XUKFIS from the Structure Navigator on the right hand side of the main Mercury window. • Inspect the structure. Click on the Packing tick box in the bottom left-hand corner of the main window to display the unit cell of the structure. Notice that both the R and S enantiomers are present in the unit cell.

13.5.3 Compounds with tervalent chiral atoms. • Pyramidal nitrogen atoms might be expected to give rise to optical activity if they are connected to three different groups. This is because the unshared pair of electrons is analogous to a fourth group and necessarily different from the others:

• In practice, chirality is rarely observed in such systems due to pyramidal inversion. This is the rapid movement of the unshared pair from one side of the XYZ plane to the other which thus interconverts the molecule into its enantiomer. • However, inversion is less rapid for nitrogen atoms in a three membered ring, and for nitrogen atoms connected to an atom with an unshared electron pair. When both of these features are present in a molecule the barrier to inversion is sufficient to allow isolation of separate isomers. This can result in compounds which are optically active due to a chiral tervalent nitrogen atom. • An example of this is 1-chloro-2-methoxycarbonyl-2-methylcarbamoylaziridine, for which both the cis - and trans epimers have been isolated:

CSDS Teaching Modules • Examine each of these two stereoisomers in turn by clicking on their refcodes in the Structure Navigator on the right hand side of the main Mercury window. • You should be able to see that KIRCOD has a (1R,2R) configuration at the chiral N(l) and C(2) atoms, whereas the crystal structure of KUBZOW is made up of racemic pairs of discrete molecules with (1S,2R) and (1R,2S) configurations.

13.5.4 Chirality due to restricted rotation, • Some compounds are chiral, yet have no stereogenic centres. Consider 2,2'-dihydroxy-4,4',6,6'- tetramethylbiphenyl, the mirror images (enantiomers) shown below are not superimposable and so the molecule is chiral:

• The presence of the ortho substituents means that the central bond linking the two phenyl groups cannot rotate freely due to steric hindrance. This hindered rotation prevents the enantiomers from interconverting and therefore gives rise to chirality. • Examine this molecule for yourself (CSD refcodes: NIYQUH and NIYRAO ). The crystal structure of NIYQUH consists of a single enantiomer, whereas the crystal structure of NIYRAO has both enantiomers present in the unit cell (click on the Packing tick box in the bottom left- hand corner of the main window to display the unit cell of the structure). • Another example of a molecule that is chiral by virtue of restricted rotation is 2,2- bis(diphenylphosphino)-1,1'-binaphthyl , known as BINAP (CSD refcodes: PASRAC and HUZGUE ). This is an important ligand used in asymmetric hydrogenation reactions.

98 CSDS Teaching Modules • In order for the enantiomers of BINAP to interconvert, the PPh 2 group would have to force its way past either the other PPh 2 group or past the hydrogen. Both pathways are too strained for racemization to occur:

13.5.5 Chirality due to helical shape. • Helicenes are a further another example of compounds that lack asymmetric carbon atoms yet are chiral. Helicenes’ chirality results from the fact that clockwise and counterclockwise helices are non-superimposable. • Examine the following hexahelicenes (CSD refcodes: HEXHEL and MEHXHE ). In both structures see how one side of the molecule must lie above the other because of crowding.

CSDS Teaching Modules 13.6 SUMMARY OF KEY CONCEPTS • A molecule that is not superimposable on its mirror image is said to be chiral. • A chiral molecule is one that does not contain a plane of symmetry. The most common cause of chirality is the presence of a tetrahedral sp 3-hybridised carbon atom bonded to four different groups, this is referred to as a stereogenic center. • Compounds that contain such stereogenic centers exist as a pair of non-superimposable mirror image stereoisomers called enantiomers. • Enantiomers are identical in all physical properties except for the direction in which they rotate the plane of polarised light. • The configuration of a stereogenic center can be described as either R or S by applying sequence rules. • Diastereoisomers are stereoisomers that are not mirror images. Diastereoisomers have different spectra and physical properties. • Some molecules have more than one stereogenic center. Enantiomers have opposite configuration at all stereogenic centers, whereas diastereoisomers have the same configuration in at least one center but opposite configurations at the other(s). • Compounds that contain stereogenic centers but are achiral (due to a symmetry plane) are called meso compounds. • Molecules can also display optical activity due to other structural features, including:

100 CSDS Teaching Modules quadrivalent chiral atoms other than carbon, tervalent chiral atoms, restricted rotation about a particular bond, and helical shape.

CSDS Teaching Modules 102 CSDS Teaching Modules