Substitution in the phenyl ring

The two diastereomeric amides exhibit different retention times. Other l-aryl-2-aminopropanes substituted in the phenyl ring as well as a-methylbenzylamine have also been investigated by this method.[44]... 

In strongly acidic media the conjugate acid is nitrated leading to para substitution in the phenyl ring. In acetic anhydride an intermediate such as (28) may be formed, resulting in the favored 4-attack in the pyrazole ring (Fig. 9). 

In the case of 5-bromo-3,4-dimethyl-l-phenyl-l/f, 6//-pyrano[2,3-c]pyrazol-6-one (59), mixed acid nitration results not only in para substitution in the phenyl ring, but also in ipso attack at the 5-position to yield... 

Phenyloxazolo[4,5-6]pyridine (294) and 2-phenyloxazolo[5,4-6]pyridine substituted in the phenyl ring have good antiinflammatory and analgesic activity. Some compounds possess activity comparable to phenylbutazone or indomethacin without producing the irritation in the gastrointestinal tract that acidic antiinflammatory compounds cause (78JMC1158). 

Much of the work on nitration of azoles has concerned the phenyl derivatives. These substitute in the phenyl ring at positions that depend on the reaction conditions and the relationship of the phenyl ring to the heteroatoms. Preferential nitration in the phenyl ring does not necessarily mean that the azole is intrinsically less reactive than benzene, because the phenyl ring may be strongly activated by one of the heteroatoms whereas the azole is relatively weakly activated by the phenyl group. The combination of bond-order effects and relationship to the heteroatom means that the preferred sites of substitution are as shown by arrows in structures 7.37-7.42. The effect of protonation is discussed later. 

Within five years after its discovery in 1879, 7 saccharin (1) became an industrial product as the first non carbohydrate sweetener,5 and it is still holding an important position in the market.29-31 Substantial quantities are used as additives in the electroplating industry.32 Numerous synthetic approaches are known.4,29-31 More recent synthesis of 1 and derivatives substituted in the phenyl ring are based essentially on the following procedures. 

Chlorobenz[d]isothiazole-l, 1-dioxide ( pseudosaccharin chloride ) (6)3,24.25, lee, 25i, 26i, 262 displays the reactivity of a cyclic imidoyl chloride263 resembling very much carboxylic acid halides. In previous sections preparation of 3, 4, 5, 13, 68, 86, 89 from 6 has been mentioned. Derivatives of 6 substituted in the phenyl ring have been described.250 Interestingly, Meadow observed231 that crude 6 and material that contained phosphorus pentachloride reacted with thiols more readily than the pure compound. In the reaction of 6 with aromatic sulfonamides, aluminum chloride had been added for activation.252... 

It was also found by H-NMR spectroscopy that the phenyl ring in arylidenebarbiturates (5) is twisted in relation to the plane of the ylidenebarbi-turate.114115 A detailed analysis of chemical shifts of particular aromatic protons and their coupling constants with the vinyl proton leads to the conclusion that the value of the dihedral angle 6 (Fig. 9) depends on the nature and position of substitution in the aromatic ring. Ortho substitution in the phenyl ring, where steric effects predominate, results in hindrance to rotation. Thus of the two possible conformations conformer A (Fig. 10) is favored. Moreover, for o-nitro substituted derivative 5 the dihedral angle is 43°.115... 

Fig. 10. Two conformations of 5-arylidenebarbiturates o-substituted in the phenyl ring (only arylidene moiety shown).

Stepwise substitution in the phenyl rings of phosphines such as BDPP creates new diastereomeric pairs due to chirality on phosphorus. In a detailed investigation into the hydrogenation of (Z)-a-acetamidocinnamic acid, its methyl ester and dimethyl itaconate, the catalyst was prepared from [Rh(cod)Cl]2 plus 2 equiv. of (2S,4S)-BDPP or its mono-, di-, tri-, or tetrasulfonated derivative (25-28) [93],... 

Steric factors appear to be of major importance in determining activity. Ortho substitution in the phenyl ring of the 1,4-dihydropyridines restricts the phenyl group orientation such that its ring plane is perpendicular to the dihydropyridine ring to minimize steric interactions between this substituent and the... 

Pyridyl triflates in the benzenoid 3-position readily couple with terminal acetylenes (88JOC386). When the phenylacetylene is substituted in the phenyl ring by an o-amino group, the alkynylated product (56) can be cyclized by Pd(II)-catalysis to an indole, in this case to 2-(3-pyridyl)indole (89TL2581). 

The 2-phenyl derivative (261) undergoes ready electrophilic substitution in the phenyl ring selected examples are given in Scheme 44 <88JOC2898>. 

The hydrolysis of 25 borazine derivatives in dilute 90% THF-10%H2O solutions follow pseudo-first-order kinetics. The hydrolysis rates were determined using a new analytical procedure, KBrOa-KBr solutions being used to brominate the arylamine liberated. In A-phenylborazines, ortho-substitution in the phenyl ring decreases the rate of hydrolysis markedly. 

Hammett treatment showed that substitution in the phenyl ring of the sulphone influenced the reaction more than substitution in the thiol, indicating that the transition state resembles a carbanion intermediate. The second-order rate constant for the nucleophilic addition of p-MeCgH4S-to phenyl vinyl sulphone has been detected at 0-45°C, the energy, free... 

C. Substitution in the phenyl ring at the a-position raises Jg to 115 °C. Jg in the case of a naphthalene substitution has a value of 135 °C. Jg for biphenyl is 145 °C. Tg of the more sterically hindered poly(a-methylstyrene) is 175 °C and that of polyacenaphthalene is 265 °C. A further illustration of the influence of subtle changes on T g can be seen in the case of poly(butyl methacrylate)s. The normal butyl methacrylate has a T g value of 56 °C, that of secondary butyl methacrylate is 22 °C and that of isobutyl methyacrylate is 43 °C. Once more, the greater the steric interaction the higher the value of T g. 

Taking Dh h = 436 kJ moE [5] and the generic values of Drs-sr and Drs-h = 277 and 366 kJ mol" , respectively, from Table 4, a value of -19 kJ mol" is calculated for I>rs-sr - 2Drs-h + h-h)- The good agreement with the value in equation (4) supports the view that Drs-sr and Drs-h are independent of the alkyl structure. The value for Dphs-sph 2Dri,s-h + Dh-h) from present BDEs is -18 kJ mol", and also fits expression (4), but there is insufficient data to test the effects of substitution in the phenyl ring. 

---