Trisubstituted compounds

It will be observed that most syntheses yield pyrylium salts in which positions 2,4, and 6 are substituted. Since according to formulas Ib-lc these positions have a partial positive charge, it can readily be understood why electron-donating substituents (hydroxy, alkoxy, alkyl, or aryl) in these positions stabilize the pyrylium salts. Only three pyrylium salts which do not have substituents in either a-position have been reported and few unsubstituted in y or in one a-position they are less stable toward hydrolysis, and in the case of perchlorates they explode more easily, than 2,4,6-trisubstituted compounds. In fact, the former are secondary, the latter tertiary carbonium ions. This fact also explains why the parent compound (1) was prepared only in 1953. 

An unusual dependence of the structure of the reaction product on the acylating agent (catalyst and acyl group) was observed by Balaban and Nenitzeseu in the diacylation of olefins 195, where R = Me (2-methyl-2-butene ) or R = Ph (2-methylpropenyl-benzene ) strong catalysts like AlClg or SbCls promote the formation of the 2,4,6-trisubstituted compound 197, whereas weaker... 

The tautomeric behavior of compounds of type 59 has been discussed by Meyer and Vaughan. An intramolecularly hydrogen-bonded 0X0 structure has been assigned to 60 on the basis of its infrared spectrum," whereas unambiguous chemical evidence, i.e., ozo-nolysis to succimide, confirmed the isolation of 61 in the oxo form. The foregoing results may be summarized as follows potential a-hydroxypyrroles exist as pyrrolones. Substituents in the 3-position and in the 5-position favor the A and the A -pyrrolone structure, respectively, as is to be expected. For 3,4,5-trisubstituted compounds, such as 61b, the A -sti ucturc appears to be preferred. An electron-... 

It should be noted that uses of the trisubstituted organotins and uses of the mono- and disubstituted compounds do not overlap. Thus, for example, mono-and disubstituted compounds are not suitable for use as biocides, and trisubstituted compounds are not suitable as PVC stabilizers. 

Tris(trinitromethyl)-l,3,5-triazine reacts with nucleophiles such as alcohols and amines to give products in which the trinitromethyl groups are displaced in turn to yield mono, di, then trisubstituted compounds. Some of the products which have been obtained are shown in Scheme 12 <95CHE(31)596>. 

Among the routes for preparing phosphinous amides, the most frequently used method is the aminolysis of halophosphanes, most usually chlorophosphanes [32-34], because a number of such halophosphanes are easily accessible from commercial sources. These reactions usually provide the target species, i.e., trisubstituted compounds 1 in Scheme 1, in high yield. The HCl liberated from the reaction forms a salt with an organic base (either excess of the starting amine or externally added as, for example TEA or DBU, sometimes in the presence of DM AP) which is insoluble in the reaction solvent, typically diethyl ether... 

Will the other 2,4,5-things spawn 2,4,6-things that are active Without a shadow of a doubt. Chemically, they are much more difficult to synthesize. The 2,5-dimethoxy orientation made the 4-position a natural and easy target. The 2,6-dimethoxy orientation pushes for 3-substitution, and the 4-position is completely unnatural. Tricks are needed, but tricks have now been found. The above synthesis of pseudo-2C-T-4 shows one such trick. This is, in my opinion, the exciting chemistry and psychopharmacology of the next decade. Well over half of all the psychedelic drugs mentioned in Book IT are 2,4,5-trisubstituted compounds, and every one of them has a (potentially active) 2,4,6-pseudo-counterpart. 

It goes yet further. The antidepressant series of Ariadne compounds are 1 -phenyl-2-aminobutanes. Butthe 1 -phenyl is againa 2,4,5-trisubstituted compound. The 2,4,6-isomer will give rise to a pseudo-Ariadne family, and I will bet that they too will be antidepressants. The 1 -phenyl-2-aminobutane analog of t-2C-T-4 is the 2,4,6-analogue and it has been prepared as far as the nitrostyrene. It has not yet been reduced, so it is not yet been evaluated, but it could be a most remarkable psycho-pharmacological probe. 

To summarize the conclusions from the foregoing data, which of course are not sufficient for broad generalizations, we found that the additivity principle predicts reactivities of a correct order of magnitude for 1,2-disubstituted and 1,3,5-trisubstituted compounds. In general, the observed reactivities were somewhat lower than the predicted ones, with the exception of sites located para or ortho to a phenolic hydroxyl adjacent... 

The fact that methyl 2,3- and 2,6-di-O-benzyl galactopyranosides give the same 2,3,6-trisubstituted compound has been utilized in the synthesis of the trisaccharide moiety of gangliotriosyl-ceramide. The intermediate methyl lactoside having only the axial OH-4 of the galactose unit free resulted from a mixture of both penta-O-benzyl lactosides, thus avoiding the separation of the 4,6- and 3,4-O-isopropyIidene precursors [164],... 

Very little is known about the reactivity of imidazo[5,l-h]thiazoles. It seems that for 3,5-di, and 2,3,5-trisubstituted compounds, nitrosation occurs at the 7-position (64LA144). 

In the quinoline system the nature of the substituent groups also can govern the position of entry of a nucleophile. When R in 9.43A (Figure 9.43) is electron-donating, methoxyl for example, then a 2,4,7-trisubstituted compound 9.44A is obtained (Figure 9.44), because 9.43A is preferred to 9.43B but when R is electron-withdrawing, CF(CF3)2 for example, then a 2,4,6-trisubstituted compound 9.44B is obtained [115] because perfluoro-alkyl groups stabilise 9.43B relative to 9.43A. 

Tetrafluoroethene leads only to the 2,4,5-trisubstituted compound [124], which does not rearrange, whilst perfluoroisobutene gives only the 2,4,6-trisubstituted compound the 2,4,5-isomer, in this case, is probably very crowded. This variation in the orientation of trisubstitution products obtained with the aUcene used is related to the reversibility of the process and to the crowding occurring in the 2,4,5-isomer. Carbanion stabihties decrease in the series (CF3)3C > (CF3)2CF- > CT3CF2 and therefore reversibility and crowding also follow this series (Figure 9.52). 

Electron impact mass spectrometry studies of 1,3-di- and 1,2,3-tri-substituted imidazolines show ionization preferences depending on the substitution pattern (Scheme 23). Ions corresponding to R N were detected for all substrates (path 2). In 2-substituted 1,3-diarylimidazolidines, loss of substituents at C-2 ([M-R], path 3) is favored over the loss of hydrogen (path 4). In 1,2,3-trisubstituted compounds, azirinium ions (c, path 4A) were abundant, especially when R = aryl. 2-Phenylimidazolidines fragment to the characteristic tropylium ion (C7H7+, mjz 91). l-Aryl-3-benzylimidazolidines readily lose a benzyl group as radical or cation ([M-benzyl], path 1) <2000JHC57>. 

However, it was not generally possible to obtain trisubstituted compounds from phosphines (except for trimethylphosphine 19)), while the phosphites give the trisubstituted derivatives 131) easily. Later Bigorgne 19) described all the possible substitution derivatives of carbonyl nickel with trimethylphosphite and triethylphosphite. 

Finally, some chelating triphosphines (4 ), such as C6H5P[o-C6H4P-( 2115)212 and CH3P[CH2P(C6115)2]2, yield very easily the trisubstituted compounds so difficult to obtain with tertiary monophosphines. 

The di- and trisubstituted compounds 6 - 8 are obtained as statistical mixtures of cis/tram isomers. Isolation and purification of the least soluble isomer can be achieved by crystallization from 2-propanol. Single-crystal X-ray diffraction studies of 6 and 7 exhibit the cyclohexasilane ring in a slightly distorted chair conformation and the bulky -OSiMe2 u groups in equatorial sites in order to minimize non-bonding interactions (Fig. 1). 

Allenes react with dibromocarbene in a similar manner to the way they react with dichloro-carbene 1,1-di- and trisubstituted compounds afford adducts at the more highly substituted double bond, e.g. formation of 3. °... 

We have seen that vinyl silanes can be prepared by hydrosilylation of alkynes by three different mechanisms giving good control over geometry of these inevitably terminal vinyl silanes. Vinyl silanes are stable compounds and can be isolated, unlike most of the vinyl metals we have seen so far, and other ways of making vinyl silanes allow the more-or-less controlled synthesis of mono-or trisubstituted compounds with reasonable control over selectivity. These include the Peterson reaction with two SiMe3 groups on the same carbon atom 183 and, more relevant to this chapter, reactions of vinyl lithiums with silyl chlorides.44... 

The prototype of the trisubstituted compounds is (fig. 11 (VI)), with 10 electrons instead of 6. Once again, only the low lying 7Ti and 7t2 are bonding along C-0 (C-S). As expected, the more electronegative the halogen, the higher barrier. 

The orientation for nitration is correct steric hindrance will prevent formation of much 1,2,3-trisubstituted compound. 

Stronger electrophiles240 lead to di-, tri-, or tetra-substituted derivatives. Thus, nitration or bromination yield polysubstituted derivatives (Scheme 12). In the case of disubstituted products (225, 226) a 5,7-substitution pattern is observed. The trisubstituted compound 227 has also apparently been prepared by Flitsch and Kramer,234,237 who originally assigned the structure as the 5,6,7-tribromo derivative. The weight of available evidence favors the 3,5,7-tribromo structure 227 for this material, as proposed by Zupan el a/.240... 

The majority of studies have focused on MBT, DBT, and TBT, but there are a smaller number of methods for the methyl-, phenyl-, cyclohexyl-, and octyltin compounds. Although some OTCs, particularly the tetra species, are readily amenable to analysis by GC methods, the more environmentally important mono-, di-, and trisubstituted compounds require derivatization to a volatile and thermally stable analog. 

---