Answer: Provide a mechanism for the following reaction

If we examine Table 21.1, we find that the methylphenols (cresols) are less acidic than phenol itself. For example, Phenol pKa 9.89 OH 4-Methylphenol pKa 10.17 CH3 OH This behavior is characteristic of phenols bearing electron-releasing groups. Provide an explanation.

If we examine Table 21.1, we see that phenols having electron-withdrawing groups Practice Problem 21.2 (Cli or O2Ni) attached to the benzene ring are more acidic than phenol itself. Account for this trend on the basis of resonance and inductive effects. Your answer should also explain the large acid-strengthening effect of nitro groups, an effect that makes 2,4,6-trinitrophenol (also called picric acid) so exceptionally acidic (pKa = 0.38) that it is more acidic than acetic acid (pKa = 4.76).

Your laboratory instructor gives you a mixture of 4-methylphenol, benzoic acid, and toluene. Assume that you have available common laboratory acids, bases, and solvents and explain how you would proceed to separate this mixture by making use of the solubility differences of its components.

Predict the products of each of the following reactions.

The labeling experiment just described eliminates from consideration a mechanism in which the allyl phenyl ether dissociates to produce an allyl cation (Section 13.4) and a phenoxide ion, which then subsequently undergo a FriedelCrafts alkylation (Section 15.6) to produce the o-allylphenol. Explain how this alternative mechanism can be discounted by showing the product (or products) that would result from it.

What are compounds A and B in the following sequence?

p-Benzoquinone and 1,4-naphthoquinone act as dienophiles in DielsAlder reactions. Practice Problem 21.7 Give the structures of the products of the following reactions: (a) 1,4-Naphthoquinone + butadiene (b) p-Benzoquinone + cyclopentadiene

Outline a possible synthesis of the following compound.

1-Fluoro-2,4-dinitrobenzene is highly reactive toward nucleophilic substitution through Practice Problem 21.9 an SNAr mechanism. (In Section 24.5B we shall see how this reagent is used in the Sanger method for determining the structures of proteins.) What product would be formed when 1-fluoro-2,4-dinitrobenzene reacts with each of the following reagents? (a) EtONa (b) NH3 (c) C6H5NH2 (d) EtSNa

When 2-bromo-1,3-dimethylbenzene is treated with sodium amide in liquid ammonia, no substitution takes place. This result can be interpreted as providing evidence for the eliminationaddition mechanism. Explain how this interpretation can be given

(a) Outline a step-by-step mechanism for the phenylation of acetoacetic ester by bromobenzene and two molar equivalents of sodium amide. (Why are two molar equivalents of NaNH2 necessary?) (b) What product would be obtained by hydrolysis and decarboxylation of the phenylated acetoacetic ester? (c) How would you prepare 2-phenylpropanoic acid from malonic ester?

Rank the following in order of increasing acidity.

Without consulting tables, select the stronger acid from each of the following pairs: (a) 4-Methylphenol and 4-fluorophenol (c) 4-Nitrophenol and 3-nitrophenol (e) 4-Fluorophenol and 4-bromophenol (b) 4-Methylphenol and 4-nitrophenol (d) 4-Methylphenol and benzyl alcoho

What products would be obtained from each of the following acidbase reactions? (a) Sodium ethoxide in ethanol + phenol : (c) Sodium phenoxide + aqueous hydrochloric acid : (b) Phenol + aqueous sodium hydroxide : (d) Sodium phenoxide + H2O + CO2 :

Describe a simple chemical test that could be used to distinguish between members of each of the following pairs of compounds: (a) 4-Chlorophenol and 4-chloro-1-methylbenzene (c) 4-Methylphenol and 2,4,6-trinitrophenol (b) 4-Methylphenol and 4-methylbenzoic acid (d) Ethyl phenyl ether and 4-ethylphenol

Complete the following equations: (a) Phenol + Br2 999: 5 C, CS2 (b) Phenol + concd H2SO4 99: 25 C (c) Phenol + concd H2SO4 99: 100 C (d) CH3 OH p-toluenesulfonyl chloride HO (e) Phenol + Br2 99:H2O (f) Phenol O O O (g) p-Cresol + Br2 99:H2O (h) Phenol C base 6H5 Cl O (i) Phenol C6H5 O O base 2 (j) Phenol + NaH 9: (k) Product of (j) + CH3OSO2OCH3 9: (l) Product of (j) + CH3I 9: (m) Product of (j) + C6H5CH2

Predict the product of the following reactions.

A synthesis of the b-receptor blocker called toliprolol begins with a reaction between 3-methylphenol and epichlorohydrin. The synthesis is outlined below. Give the structures of the intermediates and of toliprolol. 3-Methylphenol C10H13O2Cl Epichlorohydrin C10H12O2 (CH3)2CHNH2 toliprolol, C13H21NO2

When m-chlorotoluene is treated with sodium amide in liquid ammonia, the products of the reaction are o-, m-, and p-toluidine (i.e., o-CH3C6H4NH2, m-CH3C6H4NH2, and p-CH3C6H4NH2). Propose plausible mechanisms that account for the formation of each product

The herbicide 2,4-D can be synthesized from phenol and chloroacetic acid. Outline the steps involved.

The first synthesis of a crown ether (Section 11.16) by C. J. Pedersen (of the DuPont Company) involved treating 1,2-benzenediol with di(2-chloroethyl) ether, (ClCH2CH2)2O, in the presence of NaOH. The product was a compound called dibenzo-18-crown-6. Give the structure of dibenzo-18-crown-6 and provide a plausible mechanism for its formation

Provide a mechanism for the following reaction.

Provide a mechanism for the following reaction.

The widely used antioxidant and food preservative called BHA (butylated hydroxyanisole) is actually a mixture of 2-tert-butyl-4- methoxyphenol and 3-tert-butyl-4-methoxyphenol. BHA is synthesized from p-methoxyphenol and 2-methylpropene. (a) Suggest how this is done. (b) Another widely used antioxidant is BHT (butylated hydroxytoluene). BHT is actually 2,6-di-tert-butyl-4-methylphenol, and the raw materials used in its production are p-cresol and 2-methylpropene. What reaction is used here?

Provide a mechanism for the following reaction.

Account for the fact that the Dow process for the production of phenol produces both diphenyl ether (1) and 4-hydroxybiphenyl (2) as by-products:

Predict the outcome of the following reactions:

Phenols are often effective antioxidants (see Problem 21.26 and The Chemistry of. . .Antioxidants in Section 10.11) because they are said to trap radicals. The trapping occurs when phenols react with highly reactive radicals to produce less reactive (more stable) phenolic radicals. (a) Show how phenol itself might react with an alkoxyl radical (RO) in a hydrogen abstraction reaction involving the phenolic iOH. (b) Write resonance structures for the resulting radical that account for its being relatively unreactive.

A compound X (C10H14O) dissolves in aqueous sodium hydroxide but is insoluble in aqueous sodium bicarbonate. Compound X reacts with bromine in water to yield a dibromo derivative, C10H12Br2O. The 30004000-cm-1 region of the IR spectrum of X shows a broad peak centered at 3250 cm-1 ; the 680840-cm-1 region shows a strong peak at 830-cm-1 . The 1 H NMR spectrum of X gives the following: singlet at d 1.3 (9H), singlet at d 4.9 (1H), and multiplet at d 7.0 (4H). What is the structure of X?

Compound Z (C5H10O) decolorizes bromine in carbon tetrachloride. The IR spectrum of Z shows a broad peak in the 32003600-cm-1 region. The 300-MHz 1 H NMR spectrum of Z is given in Fig. 21.3. Propose a structure for Z.

Explain why, in the case shown, the allyl group has migrated with no change having occurred in the position of the labeled carbon atom within the allyl group:

In protic solvents the naphthoxide ion (I) is alkylated primarily at position 1 (C-alkylation) whereas in polar aprotic solvents, such as DMF, the product is almost exclusively the result of a conventional Williamson ether synthesis (O-alkylation): Why does the change in solvent make a difference?In comparing nucleophilic aromatic substitution

In comparing nucleophilic aromatic substitution reactions that differ only in the identity of the halogen that is the leaving group in the substrate, it is found that the fluorinated substrate reacts faster than either of the cases where bromine or chlorine is the leaving group. Explain this behavior, which is contrary to the trend among the halogens as leaving groups in SN1 and SN2 reactions (in protic solvents).

In the case of halogen-substituted azulenes, a halogen atom on C6 can be displaced by nucleophiles while one on C1 is unreactive toward nucleophiles. Rationalize this difference in behavior.

In the SommeletHauser rearrangement, a benzyl quaternary ammonium salt reacts with a strong base to give a benzyl tertiary amine, as exemplified below: Suggest a mechanism for this rearrangement.

Hexachlorophene was a widely used germicide until it was banned in 1972 after tests showed that it caused brain damage in test animals. Suggest how this compound might be synthesized, starting with benzene.

Compound W was isolated from a marine annelid commonly used in Japan as a fish bait, and it was shown to be the substance that gives this organism its observed toxicity to some insects that contact it. MS (m/z): 151 (relative abundance 0.09), 149 (M # +, rel. abund. 1.00), 148 IR (cm-1 ): 2960, 2850, 2775 1 H NMR (d): 2.3 (s, 6H), 2.6 (d, 4H), and 3.2 (pentet, 1H) 13C NMR (d): 38 (CH3), 43 (CH2), and 75 (CH) These reactions were used to obtain further information about the structure of W: W 999: NaBH4 X 999: C6H5COCl Y 999: Raney Ni Z Compound X had a new infrared band at 2570 cm-1 and these NMR data: 1 H NMR (d): 1.6 (t, 2H), 2.3 (s, 6H), 2.6 (m, 4H), and 3.2 (pentet, 1H) 13C NMR (d): 28 (CH2), 38 (CH3), and 70 (CH) Compound Y had these data: IR (cm-1 ): 3050, 2960, 2850, 1700, 1610, 1500, 760, 690 1 H NMR (d): 2.3 (s, 6H), 2.9 (d, 4H), 3.0 (pentet, 1H), 7.4 (m, 4H), 7.6 (m, 2H), and 8.0 (m, 4H) 13C NMR (d): 34 (CH2), 39 (CH3), 61 (CH), 128 (CH), 129 (CH), 134 (CH), 135 (C), and 187 (C) Compound Z had MS (m/z): 87 (M # +), 86, 72 IR (cm-1 ): 2960, 2850, 1385, 1370, 1170 1 H NMR (d): 1.0 (d, 6H), 2.3 (s, 6H), and 3.0 (heptet, 1H) 13C NMR (d): 21 (CH3), 39 (CH3), and 55 (CH) What are the structures of W and of each of its reaction products X, Y, and Z?

Phenols generally are not changed on treatment with sodium borohydride followed by acidification to destroy the excess, unreacted hydride. For example, the 1,2-, 1,3-, and 1,4-benzenediols and 1,2,3-benzenetriol are unchanged under these conditions. However, 1,3,5-benzenetriol (phloroglucinol) gives a high yield of a product A that has these properties: MS (m/z): 110 IR (cm-1 ): 3250 (broad), 1613, 1485 1 H NMR (d in DMSO): 6.15 (m, 3H), 6.89 (t, 1H), and 9.12 (s, 2H) (a) What is the structure of A? (b) Suggest a mechanism by which the above reaction occurred. (1,3,5-Benzenetriol is known to have more tendency to exist in a keto tautomeric form than do simpler phenols.)

Open the molecular model file for benzyne and examine the following molecular orbitals: the LUMO (lowest unoccupied molecular orbital), the HOMO (highest occupied molecular orbital), the HOMO-1 (next lower energy orbital), the HOMO-2 (next lower in energy), and the HOMO-3 (next lower in energy). (a) Which orbital best represents the region where electrons of the additional p bond in benzyne would be found? (b) Which orbital would accept electrons from a Lewis base on nucleophilic addition to benzyne? (c) Which orbitals are associated with the six p electrons of the aromatic system? Recall that each molecular orbital can hold a maximum of two electrons.

Thyroxine is a hormone produced by the thyroid gland that is involved in regulating metabolic activity. In a previous Learning Group Problem (Chapter 15) we considered reactions involved in a chemical synthesis of thyroxine. The following is a synthesis of optically pure thyroxine from the amino acid tyrosine (also see Problem 2, below). This synthesis proved to be useful on an industrial scale. (Scheme adapted from Fleming, I., Selected Organic Syntheses, pp. 3133. 1973 John Wiley & Sons, Limited. Reproduced with permission.) (a) 1 to 2 What type of reaction is involved in the conversion of 1 to 2? Write a detailed mechanism for this transformation. Explain why the nitro groups appear where they do in 2. (b) 2 to 3 (i) Write a detailed mechanism for step (1) in the conversion of 2 to 3. (ii) Write a detailed mechanism for step (2) in the conversion of 2 to 3. (iii) Write a detailed mechanism for step (3) in the conversion of 2 to 3. (c) 3 to 4 (i) What type of reaction mechanism is involved in the conversion of 3 to 4? (ii) Write a detailed mechanism for the reaction from 3 to 4. What key intermediate is involved? (d) 5 to 6 Write a detailed mechanism for conversion of the methoxyl group of 5 to the phenolic hydroxyl of 6.

Tyrosine is an amino acid with a phenolic side chain. Biosynthesis in plants and microbes of tyrosine involves enzymatic conversion of chorismate to prephenate, below. Prephenate is then processed further to form tyrosine. These steps are shown here: H O CO2 CO2 CO2 O HO H HO H CO2 chorismate mutase O prephenate dehydrogenase NAD NADH CO2 O2C Chorismate Prephenate OH 4-Hydroxyphenylpyruvate CO2 NH3 OH Tyrosine aminotransferase -ketoglutarate glutamate (a) There has been substantial research and debate about the enzymatic conversion of chorismate to prephenate by chorismate mutase. Although the enzymatic mechanism may not be precisely analogous, what laboratory reaction have we studied in this chapter that resembles the biochemical conversion of chorismate to prephenate? Draw arrows to show the movement of electrons involved in such a reaction from chorismate to prephenate.(b) When the type of reaction you proposed above is applied in laboratory syntheses, it is generally the case that the reaction proceeds by a concerted chair conformation transition state. Five of the atoms of the chair are carbon and one is oxygen. In both the reactant and product, the chair has one bond missing, but at the point of the bond reorganization there is roughly concerted flow of electron density throughout the atoms involved in the chair. For the reactant shown below, draw the structure of the product and the associated chair conformation transition state for this type of reaction: O CO2 H CO2 (c) Draw the structure of the nicotinamide ring of NAD+ and draw mechanism arrows to show the decarboxylation of prephenate to 4-hydroxyphenylpyruvate with transfer of the hydride to NAD+ (this is the type of process involved in the mechanism of prephenate dehydrogenase). (d) Look up the structures of glutamate (glutamic acid) and a-ketoglutarate and consider the process of transamination involved in conversion of 4-hydroxyphenylpyruvate to tyrosine. Identify the source of the amino group in this transamination (i.e., what is the amino group donor?). What functional group is left after the amino group has been transferred from its donor? Propose a mechanism for this transamination. Note that the mechanism you propose will likely involve formation and hydrolysis of several imine intermediates reactions similar to others we studied in Section 16.8.