2-nitrobenzyl derivatives

The selective protection of hydroxyl groups is obviously most frequent in carbohydrate synthesis and, in fact, photosensitive protecting groups have been used to this effect in oligosaccharide synthesis, nucleotide synthesis, and saccharide modification. Here, as well as in other Sections, special attention will be devoted to 2-nitrobenzyl derivatives, whose re-... 

On many occasions, and this is certainly correct for 2-nitrobenzyl derivatives, photocleavable groups can be eliminated under mild conditions (aqueous media, neutral pH, and low temperature). Frequently, at a sufficiently long wavelength, only the bond designated for cleavage is affected by irradiation, so that, whenever the irradiation itself and the photoproducts formed are not harmful to the biological system (such as cells,... 

Photolabile linkers for amides are most often based on 2-nitrobenzyl derivatives (Table 3.10 for the preparation of these and similar linkers, see also [147,153,235]). The mechanism of photolysis is the same as for the related 2-nitrobenzyl alcohol linkers (Section 3.1.3). 

The imidazole on the histidine side chain may be protected as a 2-nitrobenzyl derivative which leads to a nnixture of N"- and N -derivatives. Generally, the x-derivative dominates, and can often be isolated pure by recrystaUization. The group is installed by reaction of the silver salt of Boc-His-OMe (13) with 2-nitrobenzyl bromide in refluxing benzene (Scheme 20).b l The product 14 was immediately saponified and, after acidification, extracted into ethyl acetate to give the acid in yield 60-70%. Photolysis of this material was affected by irradiating a 0.001 M solution in dioxane for 1 hour with Pyrex-filtered UV light from a mercury vapor lamp to give Boc-His-OH in quantitative yield. 

Photolysis of o-Nitrobenzyl Derivatives and Related Compounds. - Although novel types of photolabile protecting groups are continually being developed, the 2-nitrobenzyl system remains popular, especially for photocleav-able linkers in solid-state synthesis or for the photo-induced released of so-called caged molecules. In the period under review, there were few mechanistic studies of the photolysis of 2-nitrobenzyl derivatives, but some significant applications were described. 

A photolabile fluorescent 2-nitrobenzyl derivative that releases a 5 -silylated... 

Our study was based initially on 2-nitrobenzyl derivatives. Cleavage of this group occurs at 350 nm. The mechanism involves an intramolecular redox reaction i.e., the transfer of an oxygen from the nitro group to the benzylic carbon atom. This is... 

The 2 -0-(2-nitrobenzyl) derivatives of adenosine and cytidine, which are normally prepared using 2-nitrophenyldiazomethane and tin(ii) chloride (see Vol. 9, p. 163), have now been prepared using 2-nitrobenzyl bromide and sodium hydride in DMF. These ethers are of interest because they are readily removed by photolysis in methanol-DMF. 

The intermediacy of nitrobenzyl carbanions in such photolysis is general, and also has been found in the photooxygenation of a series of nitrobenzyl derivatives including 2-methoxy-(m- and p-nitrobenzyl) ethanols95. 

This new type of photoredox reaction of p- and m-nitro-substitutcd aromatic derivatives is not observed in organic solvents, and is99,100 extended to m-nitrobenzyl derivatives 162 containing alcohol, alkyl ether, ester or amine functions these compounds undergo photooxidation to produce m-nitrobenzaldehyde (or m-nitroacetophenone) as the major isolable product100 (equation 79). 

A general reaction mechanism for m-nitrobenzyl derivative is proposed (Scheme 8) which involves a non-Kekule intermediate100. The mechanism for the p-nitrobenzyl alcohol involves the highly polarized intermediate 163, which is consistent with the observed strong solvent effect and base catalysis of the reaction (equation 80). 

Even though most commonly used photoremovable protecting groups in applications are based on o-nitrobenzyl derivatives, the mechanistic details of photorelease from nitrobenzyl derivatives were not known. Recently, Wirz et al. and Corrie et al. investigated the mechanism. The mechanism of photorelease from the photo-enols formed by irradiating 2-nitrobenzoyl compounds is more complex than for o-alkyl arylketones. 

Electrophilic substitution of benzylpyridines occurs in the benzyl ring. Nitration of 4-benzylpyridine in ca. 85% sulfuric acid gives products in the ratio ortho 14%, meta 6% and para 80% (71JCS(B)712). Nitration of 1- and 4-benzylisoquinolines gives p-nitrobenzyl derivatives. 

The esters produced by these derivatizing reagents usually enable the sensitive determination of their parent acids in foods, with detection limits occasionally comparable to those provided by intrinsically more sensitive techniques, such as electrochemistry. The UV (254 nm) and electrochemical detection (1.1 V) limits of the p-nitrobenzyl derivatives of lactic, formic, and acetic acid are the same, and are equal to 1.8, 0.9, and 1.1 ng, respectively (45). 

Method 2 (p-nitrobenzyl ester). To the residue are added 3 ml of ethanol and a 20-fold excess of 1 -p-nitrobenzyl-3-p-tolyltriazene [43]. The contents are mixed, loosely covered and heated at a gentle reflux for 1 h. The solution is cooled and an aliquot portion is subjected to chromatography. The derivatives are non-polar compared to the reagent and the parent fatty acid, and may be separated on silica gel with non-polar solvents such as hexane-diethyl ether. HPLC should also be useful with a system similar to that used for the benzyl esters. The limits of detection of the p-nitrobenzyl derivatives should be significantly lower than those of the benzyl esters. 

A series of 11 nitrobenzaldehydes was examined by TGA, DSC and ARC techniques. Only 5-hydroxy-2-nitrobenzaldehyde decomposed exothermally in an unsealed container, but all did so in sealed capsules, under dynamic, isothermal or adiabatic conditions, with evolution of much gas. Initial decomposition temperatures in °C (compound, ARC value, and DSC value at 10°/min, respectively, followed by ARC energy of decomposition in kJ/g) were - 2-nitro-, 176, 220, 1.44 3-nitro-, 166, 218, 1.94 4-nitro-, 226, 260, 1.27 2-chloro-5-nitro-, 156, 226,. 697 2-chloro-6-nitro-, 146, 220,. 832 4-chloro-3-nitro-, 116, 165, 1.42 5-chloro-2-nitro-, -, 240, - 3-hydroxy-4-nitro-, -, 200, - 4-hydroxy-3-nitro-, -, 200, - 5-hydroxy-2-nitro-, -, 175, - 3-methoxy-4-nitrobenzaldehyde, -, 245°C, -. 4-Nitrobenzaldehyde showed by far the highest self-heating rate in ARC tests (approaching 100°/min at 240°C) anf the final pressure exceeded 170 bar when the pressure relief operated. The results are compared with those from various nitrobenzyl derivatives. 

Benzylic electrophiles bearing electron-withdrawing groups at the arene do not always yield the expected products of nucleophilic substitution on treatment with a nucleophile. One important side reaction is the dimerization of these compounds to yield 1,2-diarylethenes (stilbenes). This dimerization does not require such highly activated systems as the example sketched in Scheme 4.28, but can even occur with, for example, 2- or 4-nitrobenzyl chloride [120, 121]. The latter compounds are converted into the corresponding stilbenes by treatment with KOH in ethanol [120]. Di-arylmethyl halides behave similarly and can yield tetraarylethenes on treatment with a base. These reactions presumably proceed via the mechanism sketched in Scheme 4.27, in which the amphiphilic character of the nitro group plays a decisive role (metalated nitroalkanes or 4-nitrobenzyl derivatives can act as nucleophiles and as electrophiles). 

Different heterocyclic analogues of /7-nitrobenzyl derivatives have been described to react with nucleophiles by the S lmechanism. 

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