The angle of nucleophilic attack on aldehydes and ketones

Any other portions of the molecule that get in the way of (or, in other words, that cause steric hindrance to) the Biirgi-Dunitz trajectory will greatly reduce the rate of addition and this is another reason why aldehydes are more reactive than ketones. The importance of the Biirgi-Dunitz trajectory will become more evident later—particularly in Chapter 34. 

Nucleophilic attack by the hydride ion, H , is not a known reaction. This species, which is present in the salt sodium hydride, NaH, is so small and has such a high charge density that it only ever reacts as a base. The reason is that its filled 1 s orbital is of an ideal size to interact with the hydrogen 

Although we now know precisely from which direction the nucleophile attacks the C=0 group, this is not always easy to represent when we draw curly arrows. As long as you bear the Biirgi-Dunitz trajectory in mind, you are quite at liberty to write any of the variants shown here. 

Nevertheless, adding H to the carbon atom of a C=0 group would be a very useful reaction, as the result would be the formation of an alcohol. This process would involve going down from the aldehyde or ketone oxidation level to the alcohol oxidation level (Chapter 2, pp. 25-36) and would therefore be a reduction. It cannot be done with NaH, but it can be done with some other compounds containing nucleophilic hydrogen atoms. 

In Chapter 4, we looked at isoelectronic BH3 and CHj. Here, we haws effectivaly j ust added H to both of them. 

The size of substituents plays a role in very many organic reactions—it s the reason aldehydes (with an H next to the C=0 group) are more reactive than ketones, for example. Steric hindrance affects reaction rates, but also makes molecules react by completely different mechanisms, as you will see in the substitution reactions in Chapter 15. You will need to get used to thinking about whether the presence of large substituents, with all their filled C—H and C—C bonds, is a factor in determining how well a reaction will go. 

The reversibility of cyanohydrin formation is of more than theoretical interest. In parts of Africa the staple food is cassava. This food contains substantial quantities of the glucoside of acetone cyanohydrin (a glucoside is an acetal derived from glucose). We shall discuss the structure of glucose later in this chapter, but for now, just accept that it stabilizes the 

The glucoside is not poisonous in itself, but enzymes in the human gut break it down and release HCN. Eventually 50 mg HCN per 100 g of cassava can be released and this is enough to kill a human being after a meal of unfermented cassava. If the cassava is crushed with water and allowed to stand ( ferment ), enzymes in the cassava will do the same job and then the HCN can be washed out before the cassava is cooked and eaten. 

The cassava is now safe to eat but it still contains some glucoside. Some diseases found in eastern Nigeria can be traced to long-term consumption of HCN. Similar glucosides are found in apple pips and the kernels inside the stones of fruit such as peaches and apricots. Some people like eating these, but it is unwise to eat too many at one sitting  

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