Pharmacist Blog about what I encounter and find useful/interesting

I currently have examinations so I'll have a break from blogging.

Alkanes and radicals Addition of radicals on an alkene Look at the two reactions below, the first reaction is in normal circumstances, which will result in a normal Markovnikov reaction  ( with the addition of a   protic acid  HX to an  alkene , the acid hydrogen (H) becomes attached to the carbon with fewer   alkyl   substituents , and the  halide  (X) group becomes attached to the carbon with more alkyl substituents). In the second reaction, peroxide is used as condition, this will result in an anti-Markovnikov  reaction. The peroxide will generate Br radicals in small amounts (this is the initiation for this anti-reaction).  Let's see the peroxide mechanism in detail. As stated above, an alkyl peroxide is a radical initiator. The electrophile will add on the sp2 carbon which carries the most hydrogens (where also the radical with most alkyl groups will be formed). The termination reactions will have several other outcomes....

Alkanes and radicals Selectivity & reactivity principle Radical bromation is more selective than radical chlorination. Have a look on following illustrations to get more insight in this process: Why is it that the Bromation radical is more selective? This can be explained using the Hammand postulate. Bromation is an endothermic process, while chlorination is exothermic . The postulate states the following: Endothermic process: a rather productish (radical) transition state Exothermic: a rather reagentic (alkane) transition state Thus the Bromine atom can see the difference between the 1°, 2° and 3° hydrogens more clearly.  The more reactive a particle is, the less likely it will react selective. ( More reactivity = less selectivity, vice versa ). Alkanes undergo Bromation and Chlorination, but no Fluoration or Iodisation. Iodisation simply does not occur, and Fluoration is a way to heavy reaction to be useful.

Alkanes & radicals Relative stabilities of alkyl radicals Alkyl  groups stabilize carbocations about 5 to 10 times better than when alkyl groups have to stabilize radicals:  Radicals: Resonance >> Hyperconjugation Carbocations: Hyperconjugation >> Resonance Hyperconjugation makes the carbocations more stabilized than when hyperconjugation occurs with radicals (not so stable). This is explained due to the fact that in carbocations, both electrons sit in the same binding orbital, with radicals however, one of the electrons is sited in the anti-binding orbital.  Product spread The product spread (product outcome) is determined by CHANCE and REACTIVITY. The chance (or probability) is based on the relative amount of primary and secundary protons (in the example below 6:4), but secundary hydrogens are more reactive than primary hydrogens, this means both chance and reactivity determine the outcome of the reaction.  Thus to det...

Alkanes and radicals Introduction Let's start with one of the most complex compounds consisting of alkanes and cycloalkanes (naftenes) that can be separated by distillation: Petroleum . Some tips when writing reactions with radicals, have a look on these reactions below, when an heterolytic bond gets cleaved, the arrowhead gets two barbs. When there is a homolytic bond that gets cleaved the arrowhead that shows the direction of the radical, gets one barb, have a look: Alkanes are little reactive, they will not react fast and heavily, because they only contain strong  sigma  σ bindings (single bonds). They also only have non-partial charged atoms. Although, alkanes DO react with Cl2 and Br2. The reactions are listed below, have a look, first the actual reaction, then shown in detail with different steps : 

Alkylhalides: Substitution Nucleophile substitution reaction ( Sn1 reaction ) Sn1 side reactions I will now discuss some side reactions that can occur when a Sn1 reaction takes place. Carbocation shift Illustrated in the scheme below: Benzyl- and allylhalides  Benzyl- and allylhalides can undergo Sn1 AND Sn2 reactions. How to distinct them? Sn1 conditions: protic solvent and by adding a weak attacking nucleophile. Note: Benzyl- and allylhalides easily undergo Sn1 reactions, because their carbocations are very stable. Sn2 conditions: aprotic solvent and by adding a strong attacking nucleophile. Note: tertiary benzylhalides and tertiary allylhalides will NOT undergo a Sn2 reaction because of the steric effects (see chapter Sn2 reaction blogposts). Sn2 reaction examples Sn1 reaction examples Sn1 and Sn2 reactions in biology, nature and medicines S-Adenosyl methionine This is a biological methylating agens, also known as SAM . It is a frequen...

Alkylhalides: Substitution Nucleophile substitution reaction ( Sn1 reaction ) Solvent effects To start off, have a look on the rate determing step of the Sn1 reaction, what happens with the compound becoming split into 2 ions: The dielectric constant is a measure on how the solvent insulates the opposite charges from eachother. F.e. water will either contain the positive charged ion by using its partial negative oxygen, and it will contain the negative charged ion by using its partial positive hydrogen, thus separating both ions from eachother. A visual picture below from the Organic Chemistry book from Bruice found below to clear this up, on the left side the negative ion gets contained, on the right side the positive ion.  Relative rates of water and ethanol solvents are the following: 100% water    1200 80% water / 20% ethanol   400 50% water / 50% water   60 100% ethanol   10 In the next blog post it wi...