Phenyl substituent

Aryl substituents enhance somewhat the reactivity of the ring atoms, the phenyl substituent being arylated in a proportion of 40 to 60% (396,406, 407). 

Additional phenyl substituents stabilize carbocations even more Triphenylmethyl The triphenylmethyl group is 1, , t 11 1. . 1. .. 

Aryl halides react too slowly to undergo substitution by the Sn2 mechanism with the sodium salt of diethyl malonate and so the phenyl substituent of phenobarbital cannot be introduced in the way that alkyl substituents can... 

Polystyrene with its bulky phenyl substituents shows the largest amount of hindrance of the polymers listed here. 

Researchers at Du Pont used hydroquinone asymmetrically substituted with chloro, methyl, or phenyl substituents and swivel or nonlinear bent substituted phenyl molecules such as 3,4- or 4,4 -disubstituted diphenyl ether, sulfide, or ketone monomers. Eor example,... 

Nitration of pyrazolones and alkoxypyrazoles takes place at the 4-position (or in the para position of the 1-phenyl substituent) (B-76MI40402). Treatment of propyphenazone (296) with fuming nitric acid results in at least 27 products (81AP532), amongst them (297) which was identified by H and C NMR data. 

A mechanism has been proposed to rationalize the results shown in Figure 23. The relative proportion of the A -pyrazolines obtained by the reduction of pyrazolium salts depends on steric and electronic effects. When all the substituents are alkyl groups, the hydride ion attacks the less hindered carbon atom for example when = Bu only C-5 is attacked. The smaller deuterohydride ion is less sensitive to steric effects and consequently the reaction is less selective (73BSF288). Phenyl substituents, both on the nitrogen atom and on the carbon atoms, direct the hydride attack selectively to one carbon atom and the isolated A -pyrazoline has the C—C double bond conjugated with the phenyl (328 R or R = Ph). Open-chain compounds are always formed during the reduction of pyrazolium salts, becoming predominant in the reduction of amino substituted pyrazoliums. 

Another example of the analogy between pyrazole and chlorine is provided by the alkaline cleavage of l-(2,4-dinitrophenyl)pyrazoles. As occurs with l-chloro-2,4-dinitrobenzene, the phenyl substituent bond is broken with concomitant formation of 2,4-dinitrophenol and chlorine or pyrazole anions, respectively (66AHC(6)347). Heterocyclization of iV-arylpyrazoles involving a nitrene has already been discussed (Section 4.04.2.1.8(i)). Another example, related to the Pschorr reaction, is the photochemical cyclization of (515) to (516) (80CJC1880). An unusual transfer of chlorine to the side-chain of a pyrazole derivative was observed when the amine (517 X = H, Y = NH2) was diazotized in hydrochloric acid and subsequently treated with copper powder (72TL3637). The product (517 X = Cl, Y = H) was isolated. 

Some active 5-pyrazolone derivatives (707) and (708) in which the 1-phenyl substituent of antipyrine was replaced by 2 -, 3 - and 4 -pyridyl groups have been prepared (66HCA272). A series of aminoesters substituted at the nitrogen atom of the ester grouping with an antipyryl residue (709) were found to possess local anesthetic properties (69MI40400). 

Benzisoxazole and its simple alkyl derivatives are liquids with b.p. s of 84°C/11 mmHg for the unsubstituted system, 92.5°C/11 mmHg for the 3-methyl compound, and 117 °C/11 mmHg for the 4,6-dimethylbenzisoxazole. 2,1-Benzisoxazole is also a liquid, b.p. 94.4-94.5 °C/11 mmHg, and its 3-methyl derivative has a b.p. of 115.5-116 °C/11 mmHg. Introduction of a 3-phenyl substituent in both systems results in crystallinity, with m.p. s of 83-84 °C and 52-53 °C, respectively. Polar substituents, as anticipated, also impart crystallinity to these systems. 

Under carefully controlled conditions, nitration of 3,5-diphenylisoxazole in AC2O/HNO3 at 20°C gave 4-nitro-3,5-diphenylisoxazole. However, 3,5-diphenylisoxazole in HNO3 underwent nitration first at the para position of the 5-phenyl substituent and then at the meta position of the 3-phenyl group (74KGS597). 

As would be anticipated, amino groups in the homocyclic ring of 1,2-benzisoxazoles behave as normal aromatic amines, forming mono- and bis-acyl derivatives, etc. (67AHC(8)277,p. 296). In th e isomeric 2,1-benzisoxazoles the 3-amino compound exists as such and not in the tautomeric 3-imino form (65CB1562). Amino groups in 3-phenyl substituents behave as normal aromatic amines (67AHC(8)277,p. 331). 

Both 1,2- and 2,1-benzisothiazoles react with electrophiles to give 5- and 7-substituted products (see Section 4.02.3.2). The isothiazole ring has little effect on the normal characteristics of the benzene ring. C-Linked substituents react almost wholly normally, the isothiazole ring having little effect except that phenyl substituents are deactivated (see Section 4.17.2.1). There are, however, considerable differences in the ease of decarboxylation of the carboxylic acids, the 4-isomer being the most stable (see Section 4.02.3.3). 

The isothiazole ring causes deactivation of phenyl substituents, particularly in 3-phenyl-isothiazoles. Nitration of arylisothiazoles, however, occurs only in the benzene ring, the pattern of substitution varying greatly with the position of the aryl group on the isothiazole... 

The 1-azirines obtained from the vapor phase pyrolysis of 4,5-disubstituted 1-phthalimido-1,2,3-triazoles (157) have been found to undergo further thermal reactions (71CC1S18). Those azirines which contain a methyl group in the 2-position of the ring are cleaved to nitriles and phthalimidocarbenes, whereas those azirines which possess a phenyl substituent in the 2-position rearrange to indoles. 

If there is no phenyl substituent in the 3-position the amination ability decreases. The acyloxaziridine (104) yields only 11% of a semicarbazide derivative with piperidine. In the presence of strong bases an intramolecular amination competes. Compound (104) reacts with methoxide within a couple of seconds to give phenylhydrazine carboxylic ester (106), and with cyclohexylamine to give the substituted semicarbazide (107). A diaziridinone (105) is assumed to be the common intermediate, formed by an intramolecular reaction from deprotonated (104) (67CB2600). 

Alkenes lacking phenyl substituents appear to react by a similar mechanism. Both the observation of general acid catalysis and the kinetic evidence of a solvent isotope effect are consistent with rate-limiting protonation with simple alkenes such as 2-metlQ lpropene and 2,3-dimethyl-2-butene. 

Table 11.2. Effect of Phenyl Substituents on Activation Enthalpy and Entropy of Cope...

The most advanced MO and DFT calculations support the idea of an aromatic transition state. The net effect on reaction rate of any substituent is determined by whether it stabilizes the transition state or the ground state more effectively. The aromatic concept of the transition state predicts Aat it would be stabilized by substituents at all positions, and this is true for phenyl substituents, as shown in Table 11.2. 

The reactivity of a series of hydrocarbons toward oxygen measured under a standard set of conditions can give some indication of the susceptibility of various structural units to autoxidation. Table 12.10 gives the results for a series of hydrocarbons. These data indicate the activating effect of alkyl, vinyl, and phenyl substituents. 

With 4,4-diarylcyclohexenones, the di-Tc-methane rearrangement occcurs. In compounds in which the two aryl groups are substituted differently, it is found that substituents which stabilize radical character favor migration. Thus, the p-cyanophenyl substituent migrates in preference to the phenyl substituent in 4 ... 

This addition to the aromatic ring is believed to be eoncerted, since the relative geometry of the substituents on the alkene is retained in the product. Lesser amounts of products involving addition to 1,2- or 1,4-positions of the aromatic ring are also formed in such photolyses. ° This type of addition reaction has also been realized intramolecularly when the distance between the alkene and the phenyl substituent is sufficient to permit interaction. 

Additional phenyl substituents stabilize carbocations even more. Triphenylmethyl... 

However, uranocene can be made more air-stable by use of sufficiently bulky substituents, and 1,3,5,7-tetraphenylcyclo-octatetraene yields the completely air-stable [U( -CgH4Ph4)2], in which the parallel ligands are virtually eclipsed but the phenyl substituents staggered and rotated on average 42° out of the Cg ring plane (Fig. 31.10). 

The mechanism of the asymmetric alkylation of chiral oxazolines is believed to occur through initial metalation of the oxazoline to afford a rapidly interconverting mixture of 12 and 13 with the methoxy group forming a chelate with the lithium cation." Alkylation of the lithiooxazoline occurs on the less hindered face of the oxazoline 13 (opposite the bulky phenyl substituent) to provide 14 the alkylation may proceed via complexation of the halide to the lithium cation. The fact that decreased enantioselectivity is observed with chiral oxazoline derivatives bearing substituents smaller than the phenyl group of 3 is consistent with this hypothesis. Intermediate 13 is believed to react faster than 12 because the approach of the electrophile is impeded by the alkyl group in 12. 

To understand the unpredictable nature of the Pictet-Gams reaction, Hartwig and Whaley conducted the first mechanistic studies in 1949. Their work focused on substituent effects when directly attached to the ethylamine side chain. They also investigated a variety of dehydration agents in order to identify optimal reaction conditions. It was determined that formation of the isoquinoline structure was virtually impossible when alkyl or phenyl substituents were placed in the 4-position of the ethylamine side chain. 

The Reimer-Tiemann reaction has also been used to formylate 2,5-dimethylpyrrole and its iV-methyl derivative and indoles having methyl, methoxyl, and phenyl substituents. Significantly, 3-methylindole gave only 3-chloro-4-methylquinoline. ... 

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