Aromatic hydrate acid-catalyzed

Ibuprofen (+) -2- (4-Isobutylphenyl) propionic acid Aromatic alkylation, HF-catalyzed aromatic acetylation, palladium-catlayzed carbonylation, alkene hydration... 

Those dihydro compounds which carry a leaving group attached to their single. vp -hybridized carbon atom exist in equilibrium with the corresponding aromatic compounds (e.g. the pseudobases 467= 468 see Section 3.2.1.6.3.iv). Another similar example is that of the covalently hydrated cations of neutral azines (see Section 3.2.1.6.3). A somewhat less obvious example is the acid-catalyzed cleavage (469) — (470) with the loss of MeC02H. 

Cyclohexadienol was prepared by Rickborn in 1970 from reaction of the epoxide of 1,4-cyclohexadiene with methyl lithium.100 A hydrate of naphthalene, 1-hydroxy-1,2-dihydro-naphthalene was prepared by Bamberger in 1895 by allylic bromination of O-acylated tetralol (1-hydroxy-l,2,3,4-tetrahydronaphthalene) followed by reaction with base.101 Hydrates of naphthalene and other polycylic aromatics are also available from oxidative fermentation of dihydroaromatic molecules, which occurs particularly efficiently with a mutant strain (UV4) of Pseudomonas putida.102,103 The hydrates are alcohols and they undergo acid-catalyzed dehydration to form the aromatic molecule by the same mechanism as other alcohols, except that the thermodynamic driving force provided by the aromatic product makes deprotonation of the carbocation (arenonium ion) a fast reaction, so that in contrast to simple alcohols, formation of the carbocation is rate-determining (Scheme 6).104,105... 

In all these cases it is possible to determine Kk directly by combining kn2o with ku, the rate constant for carbocation formation. The latter constant is readily determined spectrophotometrically by monitoring acid-catalyzed dehydration of the aromatic hydrate to the corresponding aromatic product. In principle, as we have seen, when the dehydration product is aromatic, carbocation formation is the rate-determining step of the reaction. However, the finite values of kp/kn2o for the phenanthrenonium ion and other areno-nium ions leading to moderately stable aromatic products imply a small correction for reversibility of this reaction step. 

In so far as in aqueous solution dehydration of alcohols to form alkenes is normally disfavored thermodynamically, it is clear why the rate-determining step in the acid-catalyzed dehydration (or hydration of the alkenes) is normally proton transfer. Only when the double bond of the product is strongly stabilized, for example by forming part of an aromatic ring, does deprotonation become faster than carbocation formation. 

Several examples in previous sections fall under the heading of acid-base catalysis. Nitration of aromatics with catalyst acid HB and its conjugate base B is one of these (see reaction 4.6 in Section 4.1). Also, acid-catalyzed hydrolysis and hydration reactions such as 8.3 and 8.7 can be viewed as belonging to this category because the original catalyst actually is H30+ rather than H+ and is reconstituted in a step that involves its conjugate base, H20, as co-reactant. 

On one hand, the aliphatic acetylenic alcohols are relatively stable in the acid itself (in protonated form) and undergo reaction only in the presence of an electroactive metal surface. On the other hand, aromatic acetylenic alcohols tend to react further with the acid, as well as with the metal surface, forming products which themselves are active inhibitors. - These secondary products may function as intermediates and continue to react, either on the surface or in solution, to yield an adherent low-molecular-weight polymer film. For example, 3-phenyl-2-propyn-1-ol undergoes acid-catalyzed hydrolysis (protonation and hydration) in the solution to... 

Pt-catalyzed hydration of various aliphatic and aromatic alkynes under phase transfer conditions in (CH2C1)2/H20 in the presence of Aliquat 336 led to either a Markovnikov product, mixtures of two ketones, or ketones with the carbonyl group positioned away from the bulky side.72 In the absence of the phase transfer reagent, Aliquat 336, hardly any reaction took place. Recently, a hydrophobic, low-loading and alkylated polystyrene-supported sulfonic acid (LL-ALPS-SO3H) has also been developed for the hydration of terminal alkynes in pure water, leading to ketones as the product.73 Under microwave irradiation, the hydration of terminal arylalkynes was reported to proceed in superheated water (200°C) without any catalysts.74... 

Si. rra(pentafluorophenyl)boron was found to be an efficient, air-stable, and water-tolerant Lewis-acid catalyst for the allylation reaction of allylsilanes with aldehydes.167 Sc(OTf)3-catalyzed allylations of hydrates of a-keto aldehydes, glyoxylates and activated aromatic aldehydes with allyltrimethylsilane in H2O-CH3CN were examined. a-Keto and a-ester homoallylic alcohols and aromatic homoallylic alcohols were obtained in good to excellent yields.168 Allylation reactions of carbonyl compounds such as aldehydes and reactive ketones using allyltrimethoxysilane in aqueous media proceeded smoothly in the presence of 5 mol% of a CdF2-terpyridine complex (Eq. 8.71).169... 

The microsomal epoxide hydrolases (microsomal EH, mEH), predominantly found in the endoplasmic reticulum, regio- and stereoselectively catalyze the hydration of both alkene and arene oxides, including oxides of polycyclic aromatic hydrocarbons. These enzymes have been purified to homogeneity from various species and tissues [22] [41 - 46], The human microsomal EH contains 455 amino acids (Mr 52.5 kDa) and is the product of the EPHX1 gene [47] (also known as HYL1 [48]). 

Although electrophilic reactions involving dications with deactivated arenes may suggest the formation of superelectrophilic intermediates, there are a number of well-known examples of monocationic electrophiles that are capable of reacting with benzene or with deactivated aromatic compounds. For example, 2,2,2-trifluoroacetophenone condenses with benzene in triflic acid (eq 12).13 A similar activation is likely involved in the H2SO4 catalyzed reaction of chloral (or its hydrate) with chlorobenzene giving DDT (eq 13). 

It must, nonetheless, be emphasized that the products of reduction of pyrimidine have not been unequivocally identified, largely due to their instability in the presence of air (oxygen). Furthermore, the UV absorption spectra of the reduction products of waves I and II (kmax284 nm, smax 1.5 x 103) are suggestive of rapid conversion (proton-catalyzed hydration ) of the products, since both the dimer and the dihydro derivative possess a reduced system of aromatic bonds relative to the parent pyrimidine, as a result of which the UV absorption maximum should be shifted to the violet, whereas it is, in fact, shifted 44 nm to the red (from 240 nm to 284 nm) for both products. Of possible relevance to this is the fact that the reduced rings of 4-aminopyrimidine 102) and nicotinamide 103) undergo acidic hydration to form products absorbing at 280 to 290 nm. 

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