Benzylic protons

The large sulfur atom is a preferred reaction site in synthetic intermediates to introduce chirality into a carbon compound. Thermal equilibrations of chiral sulfoxides are slow, and parbanions with lithium or sodium as counterions on a chiral carbon atom adjacent to a sulfoxide group maintain their chirality. The benzylic proton of chiral sulfoxides is removed stereoselectively by strong bases. The largest groups prefer the anti conformation, e.g. phenyl and oxygen in the first example, phenyl and rert-butyl in the second. Deprotonation occurs at the methylene group on the least hindered site adjacent to the unshared electron pair of the sulfur atom (R.R. Fraser, 1972 F. Montanari, 1975). 

When the N-1 atom of salts of type (71) bears two prochiral groups an anisochrony of protons analogous to that of diethyl acetals is observed. For instance in compound (74) the benzylic protons show chemical shifts at 8 4.98 and 5.99p.p.m. with Ja.b = 12.2Hz (690MR(1)249). 

The 4 -pyridylethyl group was found to be more effective for intemucleotide phosphate protection than the 2 -pyridylethyl group, because its cleavage proceeded with greater efficiency. It is cleaved in a two-step process acylation with PhOCOCl increases the acidity of the benzylic protons, facilitating E-2 elimination by ammonia." ... 

An interesting alternate synthesis for this agent starts with the chlorination of the benzylic carbon of 8 by means of N ( li lorosuccinimide. Treatment of the chloro compound (9) with M)Jium amide in liquid ammonia serves to remove remaining proton I ll that carbon. This carbanion (10) then performs an alkylation iiMCtlon on unreacted starting chloride. The product of this iilkylation (11) still contains a fairly acidic benzylic proton ... 

Hydrogens on carbon next to aromatic rings also show distinctive absorptions in the NMR spectrum. Benzylic protons normally absorb downfield from other alkane protons in the region from 2.3 to 3.0 5. 

Benzo-fused epoxides 20 (n = 1 or 2) underwent facile rearrangement to alcohols 21 (n = 1 or 2, respectively) upon treatment with LDA at room temperature in only 1 h, owing to the acidic nature of their benzylic protons (Scheme 5.7) [10]. Similarly, 3,4-epoxycyclooctene 23 gave alcohol 24 [11]. 

It should also be considered that in heteroaromatic compounds, and in particular in the presence of chelating groups12, there is a high tendency for the abstraction of vinylic protons before benzylic protons, for example13 ... 

The acidity of benzylic protons of aromatics complexed to transition-metal groups was first disclosed by Trakanosky and Card with (indane)Cr(CO)3 [61]. Other cases are known with Cr(CO)3 [62], Mn(CO)3 [63], FeCp+ [64, 65], and Fe(arene)2+ [31, 66] but none reported the isolation of deprotonated methyl-substituted complexes. We found that deprotonation of the toluene complex gives an unstable red complex which could be characterized by 13C NMR ( Ch2 = 4.86 ppm vs TMS in CD5CD3) and alkylated by CH3I [58] Eq. (13) ... 

This may change with extra conjugation the benzylic protons (marked H) in (11) are more acidic than those on the methyl gr jup so elimination in base gives (12) not (13). 

Compound (18) eliminates in base with the loss of the more acidic benzylic proton (22) cf (11) - also... 

The N-benzyl protons are accidentally equivalent, presenting as a singlet at 3.59 ppm and overlap with the two protons alpha to the chlorine atom which present as the heavily roofed AB part of an ABX system (i.e., eight lines) centred at 3.55 ppm. 

H n.m.r. spectra of the oils were recorded for the range of temperatures and the protons were assigned as aromatic, phenolic OH, benzylic and aliphatic. There was an increase in the percentage of aromatic protons and a decrease in the percentage of aliphatic protons as the temperature increases, while the percentage of benzylic protons remained constant (see Figure 6). 

In view of these results the experiments using styrene were repeated at lower temperatures and the study extended to the more nucleophilic analogs, a-methyl styrene, tetraphenylethylene. No significant shifts of benzyl proton peaks were observed in any of these cases, even with a 500-Hz scale expansion. 

The spectrum of styrene in toluene was compared with that in toluene containing an equimolar quantity of Zr (benzyl) 4 at 0.06 M using a sweep of 2500 Hz. The methylene doublets of styrene were in identical positions (1115 and 1230 Hz) in these spectra. Experiment (b) (Table XIX) was repeated at — 60°C using 250-Hz expansion on a 100-MHz spectrometer. The benzyl resonance was observed to shift approximately 4 Hz (relative to toluene) upheld. The lack of splitting in the latter indicates equilibrium (if any occurs) is very rapid. Finally, the effect of temperature on the systems Zr (benzyl) 4 in styrene and Zr (benzyl) 4 toluene were examined and the results are given in Table XX. They show that no specific interaction of styrene with Zr (benzyl) 4 occurs. The interaction of toluene would probably be of the type (XXIV) whereas styrene would interact similarly or in a manner shown in (XXV), both interactions would affect the environment of the benzyl protons in Zr (benzyl) 4 if they occurred to any significant... 

Temperature (°C) Benzyl protons in toluene solution Benzyl protons in styrene only... 

The configurational stability of triorganotin halides is considerably enhanced by the presence of an amine ligand that can coordinate intramolecularly with the tin atom. This was demonstrated by analysis of the 111 NMR spectrum of the stannyl bromide 47 depicted in Figure 626. Below 30 °C, both theN-methyl and the benzylic protons are diastereotopic ... 

Kinetic enolates. Alkyllithium reagents have the advantage over lithium amides for deprotonation of ketones in that the co-product is a neutral alkane rather than an amine. This bulky lithium reagent is useful for selective abstraction of the less-hindered a-proton of ketones with generation of the less-stable enolate, as shown previously for a hindered lithium dialkylamide (LOBA,12,285). Thus reaction of benzyl methyl ketone (2) with 1 and ClSifCH,), at - 50° results mainly in the less-stable enolate (3), even though the benzylic protons are much more acidic than those of the methyl group, the less hindered ones. Mesityllithium shows... 

As an extension of this work, Atkinson and co-workers (123) prepared l-dibenzylamino-l,2-dihydro-2-quinolone (78) and 1 -(/V-benzy l-N-carboxy-methyl)amino-l, 2-dihydro-2-quinolone (79). The benzylic protons of 78 showed an AB quartet that did not coalesce up to 180°C, and 79 was resolved into optical isomers. The E, for racemization was 26.2 0.4 kcal/mol. Various attempts were made to elucidate the possible pathways for isomerization in these quinolone derivatives (123). Radical dissociation, a sigmatropic shift followed by rotation, and restricted rotation about the S—N bond were excluded. The aforementioned authors (123) also excluded the possibility of nitrogen inversion and preferred restricted rotation about the N—N bond as an explanation for the existence of stereoisomers. They supported this explanation by examining the steric effects... 

Only the diagonal isomer is formed in these reactions. The structures have been elucidated by IR and H-NMR spectra of the compounds in which R = CH2Ph. In the lateral isomer, the manganese atom should be chiral and the benzylic protons should display a different shift (see below). A single signal is actually observed. 

The chirality at the transition metal is evidenced by the magnetic non-equivalence of the benzylic protons in the benzyl derivative ... 

The benzylic protons of the PNP ligands in 14 are acidic and have been deprot-onated at low temperature to give complexes 17 comprising a dearomatized. 

Evidently, reversible migration of the benzylic protons to the metal coordination sphere must be taken into account when designing catalyhc processes with such PNP pincer Hgands, in combination with iridium and other metal centers [29],... 

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