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# Tag Info

## Hot answers tagged regioselectivity

31

Thermodynamic and kinetic control This is a classic example of the concept of thermodynamic versus kinetic control of a reaction. Take a look at this energy profile diagram.1 The horizontal axis is a reaction coordinate, and the vertical axis represents Gibbs free energy. In this scenario, the starting material $\ce{A}$ can react to form either $\ce{B}$ or ...

22

First part It won't decide the issue but the Organic Chemistry text by Clayden, Greeves, Warren and Wothers also mentions that the matter might not be as clear-cut as the majority of your textbooks make it seem. This might strengthen the position of the textbook you're using a bit. But again, there are no references given. Here is the relevant passage (...

21

how is anilinium ion meta directing for electrophiles? Actually, anilinium is not meta directing (I know it is often taught that way), but rather it inductively deactivates the entire aromatic ring. To explain the electrophilic substitution pattern observed with any aromatic system we must consider both resonance and inductive effects. Resonance Effects: ...

16

Extending the pattern of epoxides to bromonium ions and mercurinium ions is hazardous at best. Below the second row (the carbon row) bond lengths get much longer, and acid strengths are much lower than compared to sulfuric acid in methanol. In general acid-catalyzed reactions involving epoxides where selectivity is a concern will have carbocation ...

16

Neither $\ce{LiAlH_4}$ nor $\ce{NaBH4}$ are able to reduce an isolated $\ce{C=C}$ bond. But if you have an enal (a conjugated aldehyde) it can react (as an electrophile) either at the $\beta$-carbon or at the carbonyle group's carbon. According to the HSAB Principle the $\beta$-carbon is a "soft" center and would react preferably with "soft" nucleophiles ...

15

This is a really interesting question and the answer is that the reaction of benzenediazonium chloride with aniline is a bit different to most of the reactions of benzenediazonium salts in that the initial product is compound 1, diazoaminobenzene. It is possible to run the reaction to isolate diazoaminobenzene prep here. These diazoaminobenzene compounds ...

14

The correct answer is the 1,2-addition product (i.e. the allylic alcohol 1). In general, Grignard reagents and organolithium reagents add directly to the carbonyl carbon, while organocuprates (organocopper reagents) add to the beta-position of an unsaturated ketone. This exact transformation was reported by Akai and coworkers recently (Org. Lett. 2010, 12, ...

13

The cyanide anion is an example of an ambident nucleophile, these are nucleophiles which, usually due to delocalisation, are able to attack an electrophile from two or more atoms. In the case of the cyanide anion reaction from carbon leads to nitriles, whilst reaction from the nitrogen leads to isocyanides. To give the full IUPAC definition from the Gold ...

13

In general, for anilines reaction at nitrogen is kinetically faster than reaction at carbon. However, the C-substituted product is usually more stable than the N-substituted product, so can prevail under thermodynamic conditions. As noted by Mayr et al. (the discussion below is taken from the same article):[1] Similar regioselectivities are found in azo ...

12

The following figure shows the resonance structures we can draw to describe the intermediates produced by electrophilic at the 2- ($\alpha$) or 3- ($\beta$) positions in pyrrole. image source You can see that the intermediate produced by attack at the $\alpha$-position can be described by 3 resonance structures. Whereas attack at the $\beta$-position ...

12

Wow, this is an amazing question. The expected reactivity is strongly dependent on the exact structure. For starters, trimethylammonium is about the size of a tert-butyl group. So, expect an A value around 4.9, which is very large. So, put that group equatorial on the ring. Once you do this, you see that there are only 2 hydrogen atoms that are anti-...

12

First of all, I should clarify that hydrogenolysis of epoxides does not always proceed with such predictable regioselectivity simply based on a switch in catalyst. Often it depends on the substituents present, as well as their relative configuration (for example, cis/trans for 2,3-disubstituted epoxides).[1] In Reaxys I find no records of the epoxide in the ...

11

The Grignard reaction, although very well examined, there are still arguments about the mechanism and the overall process. The reagent is usually best described via the Schlenk equilibrium, but that is not only dependent on $\ce{X}$, but also on the solvent: $$\ce{2RMgX <=> R2Mg + MgX2}$$ There also have been some dimeric structures reported, i.e. ...

11

Here, both the α-$\ce{CH2}$ and α-$\ce{CH3}$ groups have very similar acidities since they are both α to only one carbonyl group. [This is different compared to, for example, a 1,3-dicarbonyl such as acetylacetone, where one $\ce{CH2}$ group is α to two carbonyl groups and is therefore significantly more acidic.] In our substrate, the two protons differ very ...

10

To provide a reason for the observed regioselectivity, it is helpful to draw anthracene's aromatic π-electron system in alternance of single and double bonds. In this instance, it is more beneficial than "the ring" symbolizing the delocalised electron system, as this helps you to account for the precise number of π-electrons before the reaction (starting ...

10

For the hydroboration of isobutene there is a steric aspect: And though sterics may play some part, it doesn't explain near 100% regioselectivity. More important in determining regiochemistry, I would say, are the electronics of the transition state: Boron is electrophilic, and as such will draw the electron density of the alkene π-bond towards itself. ...

10

Cinnamaldehyde (1) does not undergo 1,4-reduction but rather 1,2-reduction with LiAlH4. The product of the reduction is 3-phenylpropan-1-ol (2). If conjugate addition were to occur, enolate 3 would be produced (stable to the reductant; enolates can be prepared to protect ketones from this reductant) and aldehyde 4 would be expected, as long as the aqueous ...

9

Unsymmetrical ketones can produce two different enolates, as shown in your reaction scheme. The enolate pictured in the top row of your drawing is referred to as the thermodynamic enolate, while the enolate shown in the bottom row of your drawing is the kinetic enolate. More highly substituted double bonds are thermodynamically more stable than less ...

9

You hit it right on the nose. The real key piece of information is that given enough time, all the unsaturated bonds will be reduced. This tells you that though the reduction is thermodynamically favorable, it is the difference in the energy barriers ($\ce{\Delta \mathrm{G^{‡}}}$) that prevents the carbonyl reduction from occurring at the same rate as the ...

9

The different reactivities of $\ce{KCN}$ and $\ce{AgCN}$ with alkyl halide, giving nitriles and isonitriles, respectively, has often been cited as a prime example of Pearson’s hard and soft acids and bases (HSAB) theory. The reasoning was that ‘hard’ electrophiles preferentially attack the ‘hard’ nitrogen centre while ‘soft’ electrophiles prefer the ‘soft’ ...

9

The addition of Grignards to propargyl alcohols occurs via the alkoxide salt, after deprotonation:[1] Here: the reactivity may be explained by the stabilising influence of complexation; the regioselectivity may be explained by the preference of a five-membered chelate ring over a four-membered one; and the stereoselectivity arises because syn addition ...

8

For the enolates that can be formed, the others have already given comprehensive answers: All four enolates are possible and since we are under thermodynamic control (weak base), we expect o observe them all. Numbering the chain carbons according to IUPAC, and noting the non-carbonyl end of the enolate, I expect the enolate ratio to be $3>6>1\approx 8$....

8

This issue is discussed in the following references: Hydrogenation of chalcones using hydrogen permeating through a Pd and palladized Pd electrodes Electrochimica Acta vol. 55, pages 5831–5839. and On the role of promoters in hydrogenations on metals; α,β-unsaturated aldehydes and ketones Applied Catalysis A: General 149 (1997) 27-48 the latter of which ...

8

Markovnikov's rule is used to predict how (for example) HX, where X is a halide, adds to an unsymmetrical olefin. As the diagram below shows, Markovnikov addition follows the rule that the "H" will add to the least substituted carbon while the "X" will add to the most substituted carbon. This is due to the fact that these reactions proceed by protonaton of ...

8

Using proline as the catalyst provides enantioselectivity to the process, but also allows N vs O regioselectivity to be controlled (though not always perfectly). Houk (and subsequently others) applied computational methods to the reaction in an attempt to understand why the nitrosobenzene was acting as an electrophile at oxygen rather than nitrogen, as ...

8

So, how do I find the most activated position in this compound? Start by drawing resonance structures of the various possible intermediates (sigma complexes) formed when $\ce{Br^{+}}$ attacks the different ring positions in p-terphenyl. Whichever intermediate has the most resonance structures is likely to be the most stable (lowest energy) intermediate. The ...

7

Given that the reaction is starting from an α,β-unsaturated ketone, the dissolving metal reduction is a very useful way of generating a particular enolate regioselectively. The mechanism dictates that only one enolate can be produced. Dissolving lithium metal in ammonia releases an electron that can add to the unsaturated system giving a radical anion. The ...

7

O-protonated phenols direct in meta, according to an article on that topic. As it occurs, phenols can be, depending on acid, protonated on oxygen, but also on carbon, and even diprotonated (but not twice on the same atom), when most powerful mixtures of HF and SbF5 are used. O-protonated forms can be brominated, hydroxylated and alkilated. C-protonated forms ...

7

The halogenation of toluene is possible by two mechanisms. In German, they are referred to by the shorthands KKK and SSS, where KKK stands for Katalysator, Kälte, Kern (catalyst, cold and core) while SSS is Sonne, Siedehitze, Seitenkette (sun, sizzling heat and side chain). At low temperatures and in the presence of an activating catalyst such as \$\ce{FeCl3}...

7

There are several arguments. Firstly, five-membered ring formation is generally kinetically more favourable than 6-membered ring formation. As ring size increases, the entropy of activation also increases – this is explained in greater detail in Clayden 2ed, pp 805–807. It is true that six-membered rings are less strained, but that is generally more of a ...

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