Substituent, aromatic

Thallium(III) acetate reacts with alkenes to give 1,2-diol derivatives (see p. 128) while thallium(III) nitrate leads mostly to rearranged carbonyl compounds via organothallium compounds (E.C. Taylor, 1970, 1976 R.J. Ouelette, 1973 W. Rotermund, 1975 R. Criegee, 1979). Very useful reactions in complex syntheses have been those with olefins and ketones (see p. 136) containing conjugated aromatic substituents, e.g. porphyrins (G. W. Kenner, 1973 K.M. Smith, 1975). 

Seemingly the presence of an aromatic substituent in the 4-position of the selenazole ring is necessary for obtaining well-crystallized products compounds with an alkyl group in the 4-position are amorphous and quite difficult to obtain as crystals. 

FIGURE 12 1 Potential energy diagram for elec trophilic aromatic substitu tion... 

Aniline and its derivatives are so reactive in elec trophilic aromatic substitu tion that special strategies are usually necessary to carry out these reactions effec tively This topic is discussed in Section 22 14... 

Isoquinoline reacts with aliphatic carboxylic acids photolyticaHy or with a silver catalyst to give excellent yields of alkylation products by decarboxylation (155). This method is useful in the synthesis of 2-benzoyhsoquinolines bearing a variety of aromatic substituents in the 1-position (156). 

R = vinyl. With aromatic substituents the fulvenes ate deep ted. The aldehyde condensation products ate also strongly colored but tesinify so easily that it is difficult to isolate them in the pure form. 

Frustrated chain packing in this approach aromatic substituents are pendantly attached to the main chain rings. 

Tertiary pyrrolines (49, = 1) and piperideines (49, = 2) (if R = H and the enamine can exist in the monomeric form or if R = aryl) evidently possess an endocyclic -double bond (79,155,156). The stretching frequency of the double bond can be lowered to 1620-1635 cm by conjugation with an aromatic substituent. The double bond of an analogous compound with aliphatic substituents in position 2 may occupy either the endo or the exo position. Lukes and co-workers (157) have shown that the majority of the five-membered-ring compounds, traditionally formulated with the double bond in a position, possess the structure of 2-alkylidene derivatives (50) with an exocyclic double bond, infrared absorption at 1627 cm . Only the 1,2-dimethyl derivative (51) is actually a J -pyrroline, absorbing at 1632 cm . For comparison, l,3,3-trimethyl-2-methylene pyrrolidine (52) with an unambiguous exocyclic double bond has been prepared (54). 

Since the rate of aliphatic acylation is higher than that of aromatic acylation, the olefin may possess aromatic substituents yields are lower, however, than with aliphatic olefins. Tlie types of olefins with aliphatic or aromatic substituents, undergoing diacylation, are shown in Table I. Systematic variation of the structure of the olefin... 

Concerning the mechanism of this reaction, calculations suggest that, in the presence of aromatic substituents on the oxazole ring, the ICI mechanism might be favored (83JA1753). 

Benzylmercaptan reacts with diacetylenes 57 under base-catalyzed conditions in aregio- and stereoselective fashion to form diadducts Z,Z-l,4-di(benzylthio)buta-1,3-dienes (59). In this case, monoadducts 58 can be isolated (96T12677). The reaction with r-butylmercaptans gives good results for diacetylenes with aromatic substituents. 

Cycloaddition of 2-nitrosopyridine 48 with nitrile oxides can give either di-A -oxides such as 49 or 3-mono-A -oxides such as 50 (93JHC287). In general, greater electron withdrawing character in the aromatic substituent appears to favor formation of the di-A -oxides. Sulfur ylides such as compound 51 are obtained from aryl isothiocyanates and l-amino-2-methylthiopyridinium iodides (84JCS(P1)1891) nitrogen ylides can be obtained from a similar reaction (86H(24)3363). 

On the basis of this successful application of 23d, this catalyst was applied in a series of reactions (Scheme 6.22). For all eight reactions of nitrones 1 and alkenes 19 in which 23d was applied as the catalyst, diastereoselectivities >90% de were observed, and most remarkably >90% ee is obtained for all reactions involving a nitrone with an aromatic substituent whereas reactions with N-benzyl and N-alkyl nitrones led to lower enantioselectivities [65]. 

Further illustration for the lack of structural specificity required for antihistaminic activity comes from the finding that ethylenediamines carrying both a benzylamine and an additional aromatic substituent on one of the nitrogens afford a series of useful therapeutic agents. Alkylation of benzylaniline with JV-... 

Ring opening occurs mainly at the least hindered carbon-nitrogen bond, unless the more hindered is activated by unsaturation or aromatic substituents 53,101,102,108). 

Cyclobutanes are cleaved less readily than are cyclopropanes, but, nonetheless, hssion occurs without difficulty if the ring has additional strain UI3,I74b,I76), adjacent unsaturation 72b,J53a), or aromatic substituents... 

Many drug-like molecules have aromatic substituents and thus have limited aqueous solubility. A routine practice is to dissolve stock drugs in a solvent known to dissolve many types of molecular structures. One such solvent is... 

The substrate scope is limited, as electron-withdrawing groups (X = p-N02 or p-CF3) on the aromatic substituent are not tolerated. However, this route does provide valuable intermediates to unnatural a-amino phosphonic acid analogues and the sulfimine can readily be oxidized to the corresponding sulfonamide, thereby providing an activated aziridine for further manipulation, or it can easily be removed by treatment with a Grignard reagent. 

For acyclic systems, the anti diastereoselectivity of the (i )-enolates is lower than the syn diastereoselectivity of comparable (Z)-enolates. For example, carboxylic acid esters, which form predominantly ( )-enolates, react with aldehydes with high anti selectivity only in those cases where bulky aromatic substituents are in the alcoholic part of the ester22 25. 

All the derivatives examined above owe their instability to the presence of the furan ring similar aldehydes, carbinols, chlorides, etc. bearing aliphatic and aromatic substituents are not prone to resinify. An analogous singularity of behaviour is encountered in furan polymers, as underlined at the beginning of this chapter. In a polymer prepared from a furan derivative three different situations must be considered ... 

The synthesis and mechanism of formation of a triazene from an arenediazonium ion and an amine with one or two aliphatic substituents (see Scheme 13-1, R = alkyl, R = H or alkyl) will be discussed in Section 13.2. Here we will briefly mention Dimroth s method (1903, 1905 a) for synthesis of wholly aliphatic triazenes (Scheme 13-6, R and R = alkyl). Dimroth obtained these by the action of Grignard reagents on alkyl azides followed by isolation via copper(i) salts. The Grignard method can also be applied for the synthesis of triazenes with an aromatic substituent by using an aryl azide. 

Also in the 1940s sulfonates without aromatic substituents were prepared [3]. Secondary alkane- or paraffmsulfonates are widely used in liquid detergents. Olefmsulfonates [4] play only a small role in Europe but found their place in the United States for household and cleaning. 

Oxa-tetrahydropyridines are interesting intermediates for the preparation of pharmaceuticals and natural product based alkaloid systems. A modified Hantzsch reaction was developed under microwave irradiation for the preparation of 2-oxa-tetrahydropyridines 173 by reaction of Meldrum s acid, a /3-ketoester and an aldehyde, using NH4OAC as the source of ammonia (Scheme 62). Yields ranged from 81 to 91% at temperatures of 100-130 °C depending on the substrate (the aldehyde) employed. All the products obtained have the same structure except for the aromatic substituent in position 4 [109]. 

Aromatics and compounds with aromatic substituents e.g. ephedrine [1, 2]... 

Dibenzobicyclo[2.2.2]octadienones (34) bearing an aromatic substituent were designed to probe the unsynunetrization of the carbonyl it orbital arising from the aromatic % orbitals [103,104], Reduction of the carbonyl moiety of 2- (R H) and 3-substituted (R3 H) dibenzobicyclo[2.2.2]octadienones (34) was studied by using sodium borohydride in methanol at - 3 °C. The 2- (34a) and 3-nitrodibenzo-bicyclo[2.2.2]octadienones (34d)... 

Halterman et al. agreed with this proposal to show the selectivity of 5-aryl-5-phenylcyclopentadiene favoring the reactions on the anti side of a more electron rich aromatic system with significant correlation between the Hammet constants for the aromatic substituents and the facial selectivity [19] (Scheme 29). 

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