P-Nitrobenzyl deriv

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. 

Similar to the pea lectin, Allen et al. [89] noted that 3-0-methyl and 3-O-benzyl glucose were better inhibitors than glucose. These studies have been extended to include p-nitrobenzyl derivatives [94]. 

In the quantitative analysis of fatty acids by HPLC a plethora of reagents have been used to increase the sensitivity of detection. The most popular derivatives formed include benzyl derivatives (Polizer et al., 1973) 2-naphthacyl derivatives (Cooper and Anders, 1974) o-and p-nitrobenzyl derivatives (Knapp and Krueger, 1975) phenacyl derivatives (Borch, 1975) p-bromophenacyl derivatives (Durst et al, 1975) methoxyphenacyl derivatives (Miller et al., 1978), and 1-naph-thylamide derivatives (Ikeda et al., 1983). The benzyl, nitrobenzyl, phenacyl, p-bromophenacyl, methoxyphenacyl, 1-naphthylamide and... 

The introduction of an extra nitrogen into the xanthine system to give 8-azaxanthines had been reported to reduce cardiovascular effects ( ) and we found that 8-azatheophylline (III) was 10 times more active than the corresponding theophylline or 6-thiotheophylline in inhibiting the rat PCA reaction whereas the other pharmacological properties were reduced in magnitude. A series of 8-azaxanthines (IT) were prepared and the best of these compounds was found to be the p-nitrobenzyl derivative (V) which was equiactive witti DSG in the rat PCA test ( ),... 

Spontaneous dimerization with elimination occurs for some carbanions by a free radical chain process. The conversion of p-nitrobenzyl derivatives to the stilbenes by the action of base occiu by the propagation steps of Scheme 17 (Russell and Pecoraro, 1979). A similar process is apparently observed for 2-(bromomethyl)-5-nitrofuran (Prousek, 1980). 

The organic derivatives of 5-nitrotetrazole form two isomers substituted either in position 1 or 2 of the ring. Some attention has been given to methyl-5-nitrotetrazoles and to 2-picryl-5-nitrotetrazole. The melting point of l-methyl-5-nitrotetrazole is 56 °C and of 2-methyl-5-nitrotetrazole is 86 °C. However 2-methyl-5-nitrotetrazole was found not to initiate RDX in a commercial detonator setup. 5-Nitro-2-(2,4,6-trinitrofenyl)tetrazole (subsequently just 5-nitro-2-picryltetrazole) has the characteristics of primary explosives but unfortunately is very sensitive to friction. The p-nitrobenzyl derivate of 5-nitrotetrazole is not a primary explosive and behaves more like a secondary explosive [4]. 

Bromobenzene, iodobenzene and benzyl chloride behave somewhat similarly. The />-nitro-derivatives of the first two compounds frequently crystallise out even before pouring into water p-nitrobenzyl chloride usually remains as an oil for several minutes before solidifying. 

The o-nitrobenzyl and p-nitrobenzyl ethers can b prepared and cleaved by many of the methods described for benzyl ethers. The p-nitrobenzyl ether is also prepared from an alcohol and p-nitrobenzyl alcohol (trifluoroacetic anhydride, 2,6-lutidine, CH2CI2, 67% yield). In addition, the o-nitrobenzyl ether can be cleaved by irradiation (320 nm, 10 min, quant, yield of carbohydrate " 280 nm, 95% yield of nucleotide ). The p-nitrobenzyl ether has been cleaved by electrolytic reduction (—1.1 V, DMF, R4N X, 60% yield) and by reduction with Na2S204 (pH 8-9, 80-95% yield). These ethers can also be cleaved oxidatively (DDQ or electrolysis) after reduction to the aniline derivative. ... 

The most interesting product arising from more drastic degradation experiments is a base, C Hi ONa, m.p. 115-120°, obtained by distilling mitragynine with zinc dust. It contains a methoxyl and a methylimino group, and has a reactive methylene group, since it forms a p-nitrobenzyl-idene derivative, m.p. 255°. This base closely resembles both ind- and jM/r-iV-methylharmine, but is not identical with either. 

We first tried to prepare 1-hydroxyyohimbine (23) and its derivatives. With 23 in hand (as described in Section II.D), its methylation with CH2N2 is carried out to provide 1-methoxy derivative 304 (77%) (Scheme 47). Utilizing K2CO3 as a base in DMF, allyl bromide, butyl iodide, and p-nitrobenzyl bromide react successfully with 23, resulting in the formation of 305 (93%), 306 (99%), and 307 (90%), respectively. All of these compounds, including 23 itself, are found to exhibit potent Q 2-blocking activity (2001H1237), and the details will be reported in due course. 

The ability of a nitro group in the substrate to bring about electron-transfer free radical chain nucleophilic substitution (SrnI) at a saturated carbon atom is well documented.39 Such electron transfer reactions are one of the characteristic features of nitro compounds. Komblum and Russell have established the SrnI reaction independently the details of the early history have been well reviewed by them.39 The reaction of p-nitrobenzyl chloride with a salt of nitroalkane is in sharp contrast to the general behavior of the alkylation of the carbanions derived from nitroalkanes here, carbon alkylation is predominant. The carbon alkylation process proceeds via a chain reaction involving anion radicals and free radicals, as shown in Eq. 5.24 and Scheme... 

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). 

A more promising approach to a synthesis of vinblastine-type compounds can be derived from the significant observation that reaction of one enantiomer of the carboline ester (-l- )-38 with p-nitrobenzyl chloro-formate and 3-methoxy-A/, A-dimethylaniline, at 25°C, gave a model (-t-)-congener of 39 in 72% yield and 55% enantiomeric excess, thus indicating a conformational retention in the nine-membered cationic intermediate formed on acylation of the carboline ester 38 (37b). 

This minor product has been now isolated and converted into the corresponding pentacyclo[5.3.0.0 .0 .0 ]decanedicarboxylic acid via intramolecular [2 - - 2] photocyclization. The material thereby obtained was converted into the corresponding cage di(p-nitrobenzyl ester) derivative via the method shown in Scheme 12. The structure of the resulting diester was established unequivocally as 40 via application of X-ray crystallographic methods (see Fig. 3.2) [28]. 

Its mononitro deriv, Bis(a, a-dimethyl-p-nitrobenzyl Peroxide, jp-03N.C6H4C(N03)20-]2> crysts(from ale), mp 158°(decompn), was prepd by Hock 8c Kropf (Ref 4)... 

The formal total synthesis of the novel /3-lactam antibiotic thienamycin has been accomplished from an isoxazoline derivative generated by [3 + 2] dipolar cycloaddition <79H(l2)l 183). Reaction of the nitrile oxide derived from 3-nitropropanal dimethyl acetal with methyl crotonate gave the isoxazoline (477) regio- and stereo-selectively. The isoxazoline was converted to amino ester (478) by hydrogenation and then to /3-lactam (479) by ester saponification and ring closure with DCC. Treatment of (479) with p-nitrobenzyl chloroformate and reaction of the derived acetal (480) with excess N-p-nitrobenzyloxycar-bonylcysteamine gave thioacetal (481), a compound which has previously been converted into ( )-(8S )-thienamycin (Scheme 106). 

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