Directing Group Preferences

These rules are very useful when trying to make new compounds. The chemist sometimes has to devise cunning plans to get groups into the correct positions on a ring. This makes interesting reading but is beyond the coverage of this text. 

This is a fast reaction and can be done with even dilute nitric acid. The reaction makes a mixture of the two products. 

If you score less than 80%, then work through the text and re-test yourself at the end using this same test. If you still get a low score then re-work the topic at a later date. 

1 The structure of C6H6 is different from a six-carbon alkane 

3 The names of all three compounds are 1,2-dimethylbenzene, 1,3-dimethylbenzene and 1,4-dimethylbenzene (see above). 

---

The focus of this chapter is the development of a technique often called wholecell matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) or whole-cell MALDI-TOF MS. Some groups prefer to use terms such as intact or unprocessed rather than whole, but the intended meaning is the same regardless of which word is used. As noted in the first chapter of this book, there are many different methods for the analysis of bacteria. However, for the analysis of intact or unprocessed bacteria, whole-cell MALDI-TOF MS is the most commonly used approach. This method is very rapid. MALDI-TOF MS analysis of whole cells takes only minutes because the samples can be analyzed directly after collection from a bacterial culture suspension. Direct MALDI MS analysis of fungi or viruses is similar in approach1,2 but is not covered in this chapter. MALDI-TOF MS of whole cells was developed with very rapid identification or differentiation of bacteria in mind. The name (whole cell) should not be taken to imply that the cells are literally intact or whole. Rather, it should be taken to mean that the cells that have not been treated or processed in any way specifically for the removal or isolation of any cellular components from any others. In whole-cell analysis the cells have been manipulated only as necessary to... 

The most conventional investigations on the adsorption of both modifier and substrate looked for the effect of pH on the amount of adsorbed tartrate and MAA [200], The combined use of different techniques such as IR, UV, x-ray photoelectron spectroscopy (XPS), electron microscopy (EM), and electron diffraction allowed an in-depth study of adsorbed tartrate in the case of Ni catalysts [101], Using these techniques, the general consensus was that under optimized conditions a corrosive modification of the nickel surface occurs and that the tartrate molecule is chemically bonded to Ni via the two carbonyl groups. There were two suggestions as to the exact nature of the modified catalyst Sachtler [195] proposed adsorbed nickel tartrate as chiral active site, whereas Japanese [101] and Russian [201] groups preferred a direct adsorption of the tartrate on modified sites of the Ni surface. 

Therefore, direct Group I methods for the determination of enantiomeric purity are generally preferred. A most important merit of the direct methods is the fact that the chiral auxiliary compounds, e.g., the chromatographic stationary phase, need not be enantiomerically pure. 

In the second approach the carbonyl function is incorporated in a chiral adjuvant (or auxiliary) which then stereoselectively directs a preferred attack of the organometallic reagent on the si- or re-faces of the carbonyl group, as determined by steric and electronic interactions. This results in two diastereoisomeric products in a ratio dependent on the relative free energies of activation. One such auxiliary is (12), derived from the readily available and optically pure ( + )-pulegone. 

In these cases, the interplay of a preferred substrate conformation as well as catalyst delivery via the catalyst-directing group form the basis for the diastereoselectivity observed... 

The green methyl group prefers to be equatorial in the transition state and directs the formatio of the two new chiral centres. The transition state (in the frame) is like a tmm-decalin with two fuse six-membered chair rings. Both new substituents go equatorial in the product while the Lewis aci binds to the oxygen and accelerates the reaction, as it would for a Diels-Alder reaction. 

It has now become clear that in the 1,3-dioxane series 17 certain compounds in which a chair conformation would require 1,3-syw-diaxial methyl groups, prefer a twist conformation n ). Unfortunately the 1,3-interactions which favour the twist conformation also lower barriers to interconversion, so that no direct nmr evidence or barriers have been obtained. 

The pATa data listed in Table 1 note that tertiary amides are mote acidic than several other functional groups, suggesting thermodynamic acidity as an important component of the mechanistic rationale for their lithiation. Indeed tertiary amides are the strongest ortho directing group, taking preference over all other functional groups tested in both intra- and inter-molecular competition experiments. - N.. A -Tetramethylphosphonic diamides also promote efficient ortho metalation. The use of tertiary amides as ortho directors was reviewed in 1982, so this discussion will focus only on developments since then. 

---