Toluene substitution pattern

An increase in toluene concentration, from 0.1tol.0M,didnot affect the substitution pattern when using acetonitrile as solvent [13]. 

GL 1] [R 4] [P 2] Variation of solvent affects also the substitution pattern to a certain extent [13], A ratio of ortho-, meta- and para-isomers for mono-fluorinated toluene amounting on average to 3.5 1 2 was found in the dual-channel micro reactor at room temperature, using acetonitrile as solvent [13]. Using methanol as solvent, the ratio was on average 5.5 1 2.4. Hence more products referring to an electrophilic substitution were formed [13]. 

Oxabicyclo [3.2.1]octenes give a poor yield of the ring-opened product in low ee if reacted at room temperature with BU2AIH in the presence of the Ni(COD)2/BINAP catalyst in either toluene or THF solution (Scheme 2-21). However, if the reaction is carried out at 60°C, high yields and enantioselectivities are obtained [78]. Various substitution patterns and protective groups are tolerated (entries 11-15). 

The first step of a free radical aromatic substitution, the formation of the a-com-plex, is also an addition step. The o,m,p-product ratio therefore also responds to steric effects. This is shown for the free radical phenylation and dimethylamination of toluene and r.-butylbenzene in Table 8. The larger the substituent on the aromatic system and the bulkier the attacking radical, the more p-substitution product is obtained at the expense of o-substitution. In the phenylation reaction the yield of m-product also increases in contrast to the dimethylamination reaction. The substitution pattern of this latter reaction is, in addition to the steric effect, governed heavily by polar effects because a radical cation is the attacking species113. ... 

Manipulation of the number of phenyl groups R1 to R3 on the rosaniline nucleus and their substitution pattern has proven a useful tool in producing a variety of commercially important derivatives. Currently, compounds with two (R1, R2 = C6H4CH3/C6H5 R3 = H) and especially three phenyl and/or toluene moieties (R1, R2, R3 = QH5/QH4CH3) are technically important. The CH3 groups are primarily located in m-position relative to the secondary amino group. 

Schneider and Rehfeuter68 have reported that enantiomerically pure 1,6-disubstituted-1,5-dienes with an aldol substitution pattern can undergo stereoselective Cope rearrangements in good yield. For example, 1,5-diene 97 underwent Cope rearrangements in toluene in sealed flasks at 180 °C for 2 h to afford, after chromatography, an 89% yield of a 97 3 diastereomeric mixture of 98 and 99, respectively (equation 54). 

The two remaining aromatic positions in 4-hydroxy-3,5-dimethoxy-toluene are analogous to the 2-position in 4-hydroxy-3-methoxytoluene, and the additivity principle would predict/0Me values of equal magnitude. The observed values differ, however, by a factor of 10. The lower reactivity of the former compound is again related to the sterically crowded substitution pattern. 

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. 

A BINOL-dimethylaminopyridine hybrid was seen to be efficient in mediating the MBH reaction (Table 5.14) [96], with optimal reaction conditions being found as —15 °C with a mixed solvent system consisting of toluene and cyclopentyl methyl ether (CPME) in a 1 9 ratio. The reaction was sensitive to the structure of the catalyst 112, the position of the Lewis base attached to BINOL, the substitution pattern of the amino group, and the length of the spacer. It should be noted that the bulky i-Pr substituent on the amino group showed the best selectivity and kinetic profile (Table 5.14, entry 5) [98]. (For experimental details see Chapter 14.10.4). 

First, one of the classical reactions of aromatic chemistry the nitration of toluene. The methyl group directs the nitration to the para position, so we get the right substitution pattern for benzocaine. But we also get the wrong oxidation levels first, the nitro group needs reducing to NH2 this can be done with catalytic hydrogenation (Chapters 22 and 24). 

Reduction of a-silyloxy ketones. a-Hydroxy ketones are reduced by zinc boro-hydride with the expected anf/-selectivity, the extent of which varies somewhat with the substitution pattern. Preparation of the isomeric, v /i-diols can be effected by reduction of the a-r-butyidiphenylsilyloxy ketones with SMEAH in toluene at —78° followed by desilylation (equation I). Again, the selectivity varies with the nature of R and R-, and is low when R is a bulky alkyl group. 

In a typical reaction, a solution of alkyne in THF is cooled to —20°C for 5 min. An equimolar amount of the dialkylzinc is added in toluene (ratio of THF toluene = 1 3). After 15 min, 10 mol % of the ligand is added, followed by the aldehyde. HPLC analysis shows complete reaction usually within 18 h. Both electron-rich and electron-poor aldehydes have been used along with aromatic and aliphatic alkynes. Yields are normally 70-90% with ee being 65-85%. Once again the optimal ligand structure may involve variation of the amine substitution pattern. 

Additions of Dialkylzinc Reagents. (lR,2S)-A/-Pyrrolidinyl-norephedrine (1) is an effective catalyst for the enantioselective addition of dialkylzinc reagents to aromatic aldehydes (eq 1). Optimized conditions involve reaction in toluene at 0°C with 10 mol % of the ligand and 2.2 equiv of the dialkylzinc reagent. Normal work-up after 20 h affords the product from addition to the Si face of the aldehyde. Product yields for a variety of alkylzinc reagents (1° and 2°) and an array of aromatic aldehydes are normally 80-100% with ee being nearly 90%. While similar results can be obtained for pyrazole-4-carbaldehydes, aliphatic aldehydes, and 1,2-phthalic dicarbaldehydes, the optimal ligand structure may involve variation of the amine substitution pattern (aliphatic tertiary amine rather than pyrrolidine structure). 

Generation of substituted aryl radical cations in the presence of nucleophiles can lead to products of side-chain substitution (processes such as anodic benzylic substitution of toluenes, which are dealt with in a separate chapter) or to products of addition to the aromatic ring itself. Nuclear addition products in /j /m-substituted systems have been proposed to form in essentially one of two ways, depending on substitution pattern and reaction conditions. Radical cations formed by electrochemical reaction (E) may be trapped by chemical reaction (C) with a nucleophile (or its anion). Repeating this sequence leads to nuclear addition products (LXV), formed by what is referred to as the ECEC mechanism [Eq. (31)] [74]. An analogous pattern may be inferred for or / (9-substituted systems. 

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