What happens when Koc (CH3) 3 is used instead of t-butoxide?
When KOC (CH3)3 is used instead, the less highly substituted alkene product predominates. Offer an explanation. The unhindered ethoxide produces the more stable alkene product (ie, the more highly substituted alkene possible). When the bulky t-butoxide is used, the most accessible hydrogen is removed.
Does bicyclooctyl 3-chloride undergo elimination with KOH?
For example, the bicyclooctyl 3º-chloride shown below appears to be similar to tert-butyl chloride, but it does not undergo elimination, even when treated with a strong base (e.g. KOH or KOC 4 H 9 ).
What is the nature of the halogen substituent on the alkyl halide?
The nature of the halogen substituent on the alkyl halide is usually not very significant if it is Cl, Br or I. In cases where both S N 2 and E2 reactions compete, chlorides generally give more elimination than do iodides, since the greater electronegativity of chlorine increases the acidity of beta-hydrogens.
What is the mechanism of elimination of 1° halide?
Rationale: A strong base or nucleophile favors SN2 or E2, but 1° halides are the least reactive halide type in elimination; therefore, only an SN2 reaction occurs. E2. Rationale: A strong, sterically hindered base cannot act as a nucleophile, so elimination occurs and the mechanism is E2
What is the reaction of benzyl halides to ethanol?
Benzyl Halide. Benzyl halides react with the sodium salt of 2-nitropropane in ethanol giving moderate to good yields (68–77%) of simple 4-substituted benzaldehydes containing substituents such as alkyl, halo, keto, cyano, ester and trifluoromethyl groups (Equation (13)) <49JA1767, 63OSC (4)932>.
What is the reaction of ammonia and halides?
The initial nucleophilic reaction of ammonia with halides occurs to generate the corresponding amines. The amine is oxidized with molecular iodine or DIH through the aldimines to the nitriles. Trichloroisocyanuric acid is also used for the same reaction. 198 In this reaction, aliphatic nitriles cannot be observed.
What are the alkylating agents of arenes?
Methyl and benzyl halides were the earliest alkylating agents for the Friedel–Crafts alkylation of arenes. In fact Friedel and Crafts themselves reported the alkylation of benzene with methyl and benzyl chloride catalyzed by AlCl3. 30 An earlier review by Price 31 covers the field until 1946, but more extensive treatment of this subject was presented by Olah in 1964 and 1973. 32 Further developments up to 1984 have been dealt with by Roberts and Khalaf in their book. 5 No repetition of the detailed and exhaustive discussion of the topic is, therefore, necessary. Instead, we point out briefly some of the significant work carried out to highlight the most important aspects of the reaction.
How are S-benzyl derivatives formed?
S-Benzyl derivatives can be formed using the robust synthesis of the appropriately substituted benzyl halide in combination with thiourea (Scheme 4 ). The tethered thiouronium salts 64–68 are routinely prepared by S N 2 reactions in 78–82% yield. Since the second synthetic step is analogous to that involving the amidinium salts ( Section 6.11.8.1.2 ), as outlined in Equation (8), a number of derivatives 69–73 can be generated in respectable yields (60–73%) <2002ARK224>. This chemistry clearly relies on the use of thiourea, which is a known carcinogenic reagent. However, when handled correctly there exists a great deal of scope, using this synthetic route, due to the number of alkyl halides commercially available.
What oxidants are used in Kornblum oxidation?
Other oxidants used in Kornblum-type oxidations include bis (4-methoxyphenyl) selenoxide < 84CL891 > and either dimethyl selenoxide or potassium benzene selenite in the presence of potassium hydrogen phosphate < 84S747 >. Excellent yields are reported for a wide range of polysubstituted benzyl halides.
What is the nucleophilic sulfhydryl group?
Glutathione is present at a concentration of about 1–5 mM in most animal cells. It participates in several enzyme-catalyzed reactions. In some reactions, glutathione acts as a reducing agent. In others, its nucleophilic sulfhydryl group reacts with certain toxic intermediates that are produced when drugs are metabolized in liver cells. The type of reaction that occurs depends on the cell type, and the nature of the enzyme that catalyzes the reaction.
Can benzyl bromides be oxidized?
However, benzyl bromides and benzyl chlorides can be directly oxidized to carboxylic acids with sodium hypochlorite (NaOCl) in the presence of TBA + HSO 4− ( Scheme 74 ). 203 Secondary benzyl halides are also converted to ketones. Oxidation of p -fluorobenzyl chloride to the corresponding carboxylic acid as a major product using NaOCl in water is ...
What oxidizing agent oxidizes benzylic carbon?
Oxidation of the Benzylic Carbon. Strong oxidizing agents such as KMnO 4 and Na 2 Cr 2 O 7 oxidize a primary or secondary benzylic carbon to the carboxy group. The only requirement here is to have at least one hydrogen on the benzylic carbon. Therefore, the oxidation only works for primary and secondary alcohols:
What is benzylic oxidation?
The benzylic oxidation is a great way preparing substituted benzoic acid s since the carboxy group cannot be added directly by electrophilic aromatic substitution and it allows achieving it through a Friedel-Crafts reaction followed by oxidation:
Why is benzylic a reactive position?
The reason for this reactivity is the resonance stabilization of the benzylic carbon regardless if the reaction goes through an ionic or radical mechanism. We will discuss each of these in the next sections.
What is the NBS in bromination?
The bromination can also be done using N-Bromosuccinimide ( NBS) like in the allylic bromination: All the halogenation reactions go by a radical mechanism and the reactivity of the benzylic carbon is again explained by its resonance-stability. Remember, radicals can also be resonance-stabilized:
Does methylation of nitrobenzene work?
Well, since the methylation of nitrobenzene does not work, we need to go the other way, i.e. install the carboxy group first and then do the nitration which will occur at the meta position since the carbonyl group is a meta director:
Is phenyl carbocation a sp2 carbon?
Don’t confuse the benzylic carbocation with the phenyl carbocation. Yes, they are both sp2 carbons but unlike the benzylic carbon, t he positive charge of the phenyl cation is a result of the empty sp2 orbital which lies perpendicular to the conjugated aromatic system and cannot be resonance stabilized: This is the reason, for example, why aryl and ...
Why does the hypothetical alkene not exist?
Because a pi-bond cannot be formed, the hypothetical alkene does not exist. Structural prohibitions such as this are often encountered in small bridged ring systems, and are referred to as Bredt's Rule . Bredt's Rule should not be applied blindly to all bridged ring systems.
What is the E2 elimination reaction?
E2 elimination reactions of certain isomeric cycloalkyl halides show unusual rates and regioselectivity that are not explained by the principles thus far discussed. For example, trans-2-methyl-1-chlorocyclohexane reacts with alcoholic KOH at a much slower rate than does its cis-isomer. Furthermore, the product from elimination of the trans-isomer is 3-methylcyclohexene (not predicted by the Zaitsev rule), whereas the cis-isomer gives the predicted 1-methylcyclohexene as the chief product. These differences are described by the first two equations in the following diagram.#N#Unlike open chain structures, cyclic compounds generally restrict the spatial orientation of ring substituents to relatively few arrangements. Consequently, reactions conducted on such substrates often provide us with information about the preferred orientation of reactant species in the transition state. Stereoisomers are particularly suitable in this respect, so the results shown here contain important information about the E2 transition state.
What color is the alpha carbon?
In both cases there are two different sets of beta-hydrogens available to the elimination reaction (these are colored red and magenta and the alpha carbon is blue ).
Is Zaitsev a good predictor?
The Zaitsev Rule is a good predictor for simple elimination reactions of alkyl chlorides, bromides and iodides as long as relatively small strong bases are used. Thus hydroxide, methoxide and ethoxide bases give comparable results.
Is E1 the same as S N 1?
Just as there were two mechanisms for nucleophilic substitution, there are two elimination mechanisms. The E1 mechanism is nearly identical to the S N 1 mechanism, differing only in the course of reaction taken by the carbocation intermediate. As shown by the following equations, a carbocation bearing beta-hydrogens may function either as a Lewis acid (electrophile), as it does in the S N 1 reaction, or a Brønsted acid, as in the E1 reaction.
Can trans-cycloalkenes be prepared?
This is similar to recognizing that trans-cycloalkenes cannot be prepared if the ring is small (3 to 7-membered), but can be isolated for larger ring systems .
Is t-butyl bromide polar or polar?
We know that t-butyl bromide is not expected to react by an S N 2 mechanism. Furthermore, the ethanol solvent is not sufficiently polar to facilitate an S N 1 reaction. The other reactant, cyanide anion, is a good nucleophile; and it is also a decent base, being about ten times weaker than bicarbonate.
What is the effect of adding triethylsilane to palladium on charcoal?
In situ generation of molecular hydrogen by addition of triethylsilane to palladium on charcoal results in rapid and efficient reduction of multiple bonds, azides, imines, and nitro groups, as well as deprotection of benzyl and allyl groups under mild, neutral conditions.
How are benzyl ethers generated?
General. Benzyl ethers can by generated using the Williamson Ether Synthesis, for example, where initial deprotonation of the alcohol and subsequent reaction with benzyl bromide delivers the protected alcohol . Use of NaH as base for the deprotonation is convenient, but when selective substitution is needed - for example, ...
What is the pathway of deprotection?
various protection and deprotection pathways. Deprotection is normally performed as palladium-catalyzed hydrogenation, delivering the alcohol and toluene. In the presence of other reducible groups, a hydrogen transfer source such as 1,4-cyclohexadiene can be used to limit the availability of hydrogen.
Can p-methoxybenzyl ethers be cleaved?
For example: p - methoxybenzyl ethers can also be cleaved using single electron oxidants such as DDQ, because the attached methoxy group stabilizes intermediates better due to resonance. Recently, a more reliable method for the use of DDQ with simple benzyl ethers has been reported using photoirradiation.
Substitution and Elimination Reactionsat The Benzylic Position
Halogenation of The Benzylic Position
- Chlorination and bromination of the benzylic position are achieved when Lewis acid catalyst are not used: The bromination can also be done using N-Bromosuccinimide (NBS) like in the allylic bromination: All the halogenation reactions go by a radical mechanism and the reactivity of the benzylic carbon is again explained by its resonance-stability. Remember, radicals can also be re…
Oxidation of The Benzylic Carbon
- Strong oxidizing agents such as KMnO4 and Na2Cr2O7 oxidize a primary or secondary benzylic carbon to the carboxy group. The only requirement here is to have at least one hydrogen on the benzylic carbon. Therefore, the oxidation only works for primary and secondary alcohols: Notice that even for longer alkyl groups the remaining carbon atoms are cleaved off in the oxidationan…
Reduction of The Benzylic Carbon
- Aryl ketones prepared by the Friedel-Crafts acylation can be reduced to alkyl benzenes by the Clemenson or Wolff-Kishner reactions: The mechanism and more details of these reactions are covered in this article. Notice also that other ketones are reduced to alcohols and only aryl ketones can be reduced to a methylene group by catalytic hydrogenation (H2+ Pt or Pd/C):
Reduction of The Nitro Group
- Even though this is not a reaction at the benzylic position, I’d still like to add here the reduction of the nitro group on a benzene ring: This reaction is important since there is no direct way of converting benzene into anilinewhich is an essential precursor in the preparation of many aromatic compounds. It is also used to prepare arenediazonium saltswhich are again a great so…
Synthetic Strategies
- The benzylic oxidation is a great way preparing substituted benzoic acids since the carboxy group cannot be added directly by electrophilic aromatic substitution and it allows achieving it through a Friedel-Crafts reaction followed by oxidation: In addition, benzene can be converted into ortho, para or a meta activated ringdepending on the order of these reactions. For example, how could …
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Significance
Example
- To see an animated display of the E2 elimination To examine Jmol models of the E2 elimination of 2-bromobutane by ethoxide base To see the effect of steric hindrance at a beta carbon on the E2 transition state
Analysis
- Having arrived at a useful and plausible model of the E2 transition state, we can understand why a bulky base might shift the regioselectivity of the reaction away from the most highly substituted double bond isomer. Steric hindrance to base attack at a highly substituted beta-hydrogen site would result in preferred attack at a less substituted site.
Mechanism
- Just as there were two mechanisms for nucleophilic substitution, there are two elimination mechanisms. The E1 mechanism is nearly identical to the SN1 mechanism, differing only in the course of reaction taken by the carbocation intermediate. As shown by the following equations, a carbocation bearing beta-hydrogens may function either as a Lewis acid (electrophile), as it doe…
Formation
- To summarize, when carbocation intermediates are formed one can expect them to react further by one or more of the following modes:
Introduction
- Having discussed the many factors that influence nucleophilic substitution and elimination reactions of alkyl halides, we must now consider the practical problem of predicting the most likely outcome when a given alkyl halide is reacted with a given nucleophile. As we noted earlier, several variables must be considered, the most important being the structure of the alkyl group …
Reactions
- The following table summarizes the expected outcome of alkyl halide reactions with nucleophiles. It is assumed that the alkyl halides have one or more beta-hydrogens, making elimination possible; and that low dielectric solvents (e.g. acetone, ethanol, tetrahydrofuran & ethyl acetate) are used. When a high dielectric solvent would significantly inf...