Thread: molecule reactivity

Hi, I am having trouble grasping the concept. If I want to find out which molecule is more reactive than another how would i go about it? is it to do with electronegativity and ionisation? for example,

Which compound would be more reactive:
tetracycline Tetracycline_structure.jpg
or minocycline minocycline.jpg (minocycline is a derivative of tetracycline)


now from what i can understand is :

minocycline would be less reactive than tetracycline as it has more CH3 groups. Which are more electronegative than the OH groups in tetracycline.

is this correct?

I would say you're correct, though I'm not sure in what sense you mean that methyl groups are more electronegative than hydroxyl groups. But in general, methyl groups are not very reactive, and hydroxyl groups are.

For example, a common reaction in organic chemistry is to expose a molecule with a hydroxy group to an acid such as , whereupon the disassociated bonds to the extra electron pair on the oxygen, creating , which then breaks off from the rest of the molecule allowing to bond at that site.

I don't know about reactivity in the absolute sense (because even though minocycline has one less -OH than tetracycline it has an added dimethyl amine, which is also a polar group) , but a famous reaction for this particular case which often results in the instability of tetracyclines under basic conditions (pH>8.5) is the intramolecular nucleophillic attack of the -OH at carbon 6, on the carbonyl opposite it (at carbon 11) and subsequent cleavage of the adjacent bond, resulting in the fomation of a lactonic structure called Isotetracycline (which is inactive as a drug). This is not possible with Minocycline, becasue there is no -OH at carbon 6, making it more stable (less reactive), under these conditions.

As a general principle, the more polarized a bond is (or the higher the difference in electronegativity between the atoms participating in a bond), the more likely it is to react, because there will be partial charges on the atoms, making the attack of nucleophiles for example, easier. These bonds are weaker, i.e. easier to break, so the molecule is more reactive.

hi, i am having trouble with chemistry again... thank god this is my last year of chem..... my question is this:

An improvement in the activity of molecule (A) has been found to be correlated with increased cationic ionisation. Provide an order of activity for the structures shown, explaining your reasoning
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I know the answer is b>a>c. but I'm not too sure why. is it because a and b are similar except for chain length and b has two amides close together so would be quite negative there and would want to make bonds?? I'm not too good at this stuff. Can someone explain it please? The whole cationic ionisation thing is throwing me off..

Are you sure that answer is correct? If it were me, I would say the most active is A, followed by B and then C, and here's my reasoning; "Cationic Ionization" means the molecule's ability to form a positive charge. The functional groups in a molecule that can form a positive charge are the basic functional groups, because these basic groups can accept a proton (an H+, i.e. a positive charge) from their medium and hence become positively charged (or "cationically ionized").

In this case, the compound with the more basic functional groups would be more cationically ionized ( I'm assuming in a physiological medium of pH around 7.4 - because the degree of ionization also depends on the pH of the medium) and therefore more active. But also, not all basic functional groups are basic to the same extent, some are more basic than others, so we also need to consider the degree of basicity. In order to understand why some groups are more basic than others, we need to understand what makes them basic at all. A base can be defined as an "electron pair donor". Which means that it has to have an atom that is capable of donating 2 electrons to, say, an H+. This is the case with Nitrogen. A Nitrogen atom has 5 outer shell electrons (it is in group 5 of the periodic table), 3 of which are participating in sigma (single) bonds (if you count the number of bonds around a nitrogen, they will always be 3), and this leaves 2 unbonded electrons; what is known as a "lone pair". It is this lone pair that can be donated to an H+. A carbon for example, on the other hand, has 4 electrons in its outer shell, and all 4 are participating in bonds, leaving no unbonded electrons, so it would have no basic properties at all. These are two extremes, but between them, basicity is graded because there are degrees of the availability of the lone pairs. This is a key concept here. Availability loosely means "localized" on the nitrogen, and not being pulled away from it by neighbouring groups. Two kinds of neighbouring groups can partially pull the electrons away from the nitrogen, namely, electron withdrawing groups (which have a high electronegativity and are always trying to pull electrons, as their name indicates), and groups that can form resonance. I don't know if you have studied about resonance or not, but it just means, again very loosely, that the electrons are "in motion" between more than one atom in a molecule. So, you can rationalize that they sort of "spends less time" (again loosely speaking) on the nitrogen, and so, they are less available to be donated by the nitrogen to an H+. An example of this is an amide function. The lone pair of the nitrogen participating in an amide is in resonance with the neighbouring carbonyl. This actually makes the amide nitrogen not basic at all. Same applies for the urea function (which is sort of like two amides fused together). They are both considered neutral.

In general, an index for the basicity of a functional group is its pka, you can look up the pka of a functional group if you are not sure of its degree of basicity. For bases, the higher the pka, the more basic the functional group is.

So now, going back to the question, we want to know which compound is most basic, because that would have the highest chance of cationic ionization, and hence, would be most active, right?
Comparing A and B, we can see that B has a urea function, which, as we explained earlier, is not basic at all. On the other hand, A has one nitrogen involved in an amide, which is again, not basic, but the other nitrogen is not involved in the amide bond (it is one carbon away), so it can donate its lone pair to an H+, making A definitely more basic than B, and hence more cationically ionized, and more active. (I'm not considering the other basic nitrogens since they are the same in all the three molecules, so they will not be the differentiating factor). Going to C, it has one nitrogen involved in an amide, which, as we said, is not basic, but not only that, it also has a free carboxyllic group ( -COOH), which is an acidic group, so this is likely to be negatively charged, which is actually quite the opposite of the effect we want for activity. So, we can then arrange the activity to be A>B>C.

HI, Thank you very much for the answer it is very thorough and actually makes sense... I got the answer from a friend who has studied chemistry longer than me so I just assumed they were right.

Can I just ask one question, can the carbonyl group not donate electrons? Oxygen has two lone pairs, are these not donated?

Thank you...