Aromatics substitution patterns

In an effort to more closely mimic the aromatic substitution pattern found in morphine (see A) the pethidine analog containing the m-hydroxy group was prepared as well. Thus, in a synthesis analogous to that used to prepare the parent compound, double alkylation of m-methoxyphenylacetonitrile with the chloroamine. 

Various phenallcylamines were shown to produce either DOM-like or AMPH-like stimulus effects the structure-activity requirements for these activities are different from the standpoints of aromatic substitution patterns, terminal amine substituents, and optical activity. Thus, it has been possible to formulate two distinct SARs. It should be realized, however, that phenalkylamines need not produce only one of these two types of effects certain phenallcylamines can produce pharmacological effects like neither DOM nor AMPH. Moreover, they can produce effects that are primarily peripheral, not central, in nature (Glennon 1987a). The fact that an agent produced DOM- or AMPH-like effects does not imply that it carmot produce an additional effect conversely, if an agent does not produce either DOM- or AMPH-like stimulus effects, it is not necessarily inactive. 

Pasti-Grigsby MB, Paszczynski A, Goszczynski S et al (1992) Influence of aromatic substitution patterns on azo dye degradability by Streptomyces spp. and Phanerochaete chrysosporium. Appl Environ Microbiol 58 3605-3613... 

The structures of vanicosides A (1) and B (2) and hydropiperoside (3) were established primarily by one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy techniques and fast atom bombardment (FAB) mass spectrometry (MS).22 The presence of two different types of phenylpropanoid esters in 1 and 2 was established first through the proton (4H) NMR spectra which showed resonances for two different aromatic substitution patterns in the spectrum of each compound. Integration of the aromatic region defined these as three symmetrically substituted phenyl rings, due to three p-coumaryl moieties, and one 1,3,4-trisubstituted phenyl ring, due to a feruloyl ester. The presence of a sucrose backbone was established by two series of coupled protons between 3.2 and 5.7 ppm in the HNMR spectra, particularly the characteristic C-l (anomeric) and C-3 proton doublets... 

Aromatic substitution patterns have been correlated fairly successfully with activation energies... 

Fig. 3.63 First order splitting patterns for aromatic protons. Data reproduced from M. Zanger (1972). The Determination of Aromatic Substitution Patterns by Nuclear Magnetic Resonance , Organic Magnetic Resonance, 4,4. Published by Heyden and Son Ltd.

The strong characteristic i.r. absorption of the S02 (or SO) group exhibited by all these compounds is clearly apparent in the spectrum of toluene-p-sulphonamide (Fig. 3.40). In addition, the absorption arising from the presence of the OH, Cl, NH2 or OR groups is usually easily assigned. The confirmation of aromatic substitution patterns by inspection of the p.m.r. spectra is described in the preparative examples below, wherein the fragmentation patterns observable in the m.s. are also discussed. 

Table 4.1 B iophore models for series from different target families and therapeutic indications. For GABA A and MM P-8 some compounds were excluded since Feature Trees do not distinguish stereoisomers or aromatic substitution patterns.

Aromatic compounds Monosubstituted Q- 3100-3000 1600-1500 770-730 (s) 710-690 (s) All show weak combination and overtone bands between 2000 and 16,500 cm-1 see aromatic substitution pattern chart... 

Obviously, proton NMR spectrometry is a powerful tool for elucidating aromatic substitution patterns—as is, 3C NMR (see Chapter 4). Two-dimensional NMR spectrometry offers another powerful tool (see Chapter 5). 

Aromatization of the enaminone moiety may sometimes be of interest as a method to yield an aromatic substitution pattern which is, not accessible starting with the aromatic compound. An example is the reaction of simple acyclic tertiary enaminones derived from acetylacetone which on treatment with gaseous HC1, are condensed to aniline derivatives211" (equation 149). 

Since the triazin-3-ones appear to be Hill reaction inhibitors and may be considered as a class of cyclic ureas, disubstitution of the aromatic ring would be expected to Increase activity. The 2-(3,4-dichlorophenyl)-1,2,4-triazin-3-one, however, was found to require >4 kg/ha for acceptable weed control, despite a respectable PI50 of 6.9 (Table II). This difference in weed control between the two compounds suggests the aromatic substitution pattern in this class is quite different from that of a "urea" like compound. This, apparently, is the case (Table III). 2,4-Disubstitution as well as the choice of halogen is important for activity. The most effective combination appears to be a fluorine at the 2-position of the aromatic ring with either a chlorine or bromine at the 4-position. However, it is only with the fluorine/bromine combination that some degree of crop tolerance is observed, and then only at the lowest acceptable weed control rate. 

Several alkaloids based on the isoindoloisoquinoline, isoind-olobenzazepine, isoindolobenzazocine and isoquinolinobenzaze-pine skeletons have been discovered. In all of these except two the aromatic substitution pattern is the same as that in tetrahydroberberine, the exceptions being related to tetrahy-dropalmatine. They are assumed to be derived from alkaloids of the berberine series, from which some transformations have been effected. 

Weigel, U.-M. and Herges, R., Automatic Interpretation of Infrared Spectra Recognition of Aromatic Substitution Patterns Using Neural Networks, J. Chem. Inf. Comput. ScL, 32, 723, 1992. 

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