[TPBN = Tetrakis (2-pyridylmethyl)-1,4 -butanediamine]
A: A substituted benzene is considered deactivated if the rate of electrophilic substitution is slower than for benzene. Activated is just the opposite, the rate of electrophilic substitution is faster than for benzene. The change in rate is attributed to the influence of the substituent on the pi-electrons of the aromatic ring. In general, if the net effect of the substituent is that it is electron withdrawing, the ring is deactivated. An electron withdrawing pulls electron density away from the aromatic ring making it electron deficient and consequently less nucleophilic. Electron donating groups push electron density toward the aromatic ring making it more electron rich and more nucleophilic.
The two components for determining if a substituent activates or deactivates the aromatic ring are its inductive and resonance effect. This is summarized on Table Table 16.2 and Figure 16.10. There is related discussion on these issue below.
Problem 16.31 asks you to predict where FC alkylation will occur on the given substituted benzene. FC alkylation is not compatible for all substituted benzenes and these limitations are noted in Figure 16.8. FC alkylation works for benzene, alkyl benzenes, phenols, anisoles, and halobenzenes. If does not work for other deactivated benzenes and for anilines. There is related discussion on this issue below.
(a) bromobenzene is slightly deactivated and there are no incompatible functional groups. It will undergo FC alkylation at the ortho or para-positions.
(b) m-bromophenol has a modest deactivating group and a strong activating group so overall it is activated. There are no incompatible functional groups. The directing effect for the two groups reinforce so you would expect FC alkylation to occur at the 4- and 6-positions
(c) p-chloroaniline, although aniline is an activating group it is incompatible with the FC alkylation reaction and therefore gives no reaction.
(d) 2,4 dichloronitrobenzene, this compound has three deactivating groups on it so it is strongly deactivated. A single nitro group is enough to prevent FC alkylation- no reaction
(e) 2,4-dichlorophenol. The two chloro groups are each modestly deactivating groups but the phenol is strongly activating. Overall, this is still an activated aromatic. There are no incompatible functional groups. The directing effect of the two chlorine atoms reinforce each other but are oppose the directing effect of the phenol. The phenol wins because it is the more powerful activator. FC alkylation occurs at the 6- position.
(f) benzoic acid is deactivated so this does not react in an FC alkylation
(g) p-methylsulfonic acid, the methyl group is a modest activator, the sulfonic acid group is a strong deactivator. The next effect is that the aromatic ring is deactivated and does not undergo FC alkylation.
(h) 2,5-dibromotoluene, The two bromine substituents are modestly deactivating while the methyl group is modest activator. The net effect is that the ring is probably not much different than benzene itself, perhaps very modestly activated, perhaps very modestly deactivated. It certainly is not strongly deactivated and there are no incompatible function groups. The directing effect of the two bromine oppose each other. The directing effect of the methyl group reinforces with the 5-bromo but is opposed to the 2-bromo. The methyl group is the stronger activating group and will direct the FC-alkylation to the 4-position.
Synthesis of 4-Trihalomethyl-2-Pyrimidinones
(aka 2,6-dimethyl-4-heptanone or ..
A: If you start with cyclohexene you can convert it to the epoxide with mCPBA. The expoxide is then opened with sodium methoxide. This is a base-catalyzed nucleophilic epoxide opening (section 18.8, page 653-4; slide 124). This gives trans-2-methoxycyclohexanol. The trans stereochemistry is because the expoxide opening is an SN2 reaction. This product is the, converted to trans-1,2-dimethoxycyclohexane by a Williamson ether synthesis (NaH and H3CI)
merck schuchardt ohg: 4-methoxy-2-nitrophenol for synthesis ..
A: This is a very complicated issue. The nature and reactivity of the nucleophiles figure into the equation as well and I think that this is beyond the scope of the course at the moment. It is based largely on experimental observations that have been formulated into a set of empirical rules rather than a theoretical analysis. It is known as hard-soft acid-base principles which takes into account the solvent conditions, the counterion and the nature of the nucleophiles and electrophiles.
To summarize the observation for conjugate (1,4-) addition versus direct (1,2-) addition:
All organometallic reagents, organolithiums, Grgnard reagents and diorganocopper reagents, will undergo direct addition to aldehydes including alpha,beta-unsaturated aldehydes.
Organolithium and Grignard reagents undergo direct addition to ketones, including alpha,beta-unsaturated ketones.