2-nitrobenzyl aldehyde

The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

Potassium and sodium borohydride show greater selectivity in action than lithium aluminium hydride thus ketones or aldehydes may be reduced to alcohols whilst the cyano, nitro, amido and carbalkoxy groups remain unaffected. Furthermore, the reagent may be used in aqueous or aqueous-alcoholic solution. One simple application of its use will be described, viz., the reduction of m-nitrobenzaldehyde to m-nitrobenzyl alcohol ... 

A similar synthesis starting with l-(2-nitrobenzyl)pyrrol-2-aldehyde used ethanol-ethyl acetate as solvent (62). Indoles are prepared in excellent yield by hydrogenation of o-nitrobenzyl ketones over Pd-on-C (i). Azaindoles are correspondingly prepared from nitropyridines (97). 

This approach offers unique opportunities for the generation of multi-functionalized cyclic 2-azadiene systems. A wide variation of the substitution pattern at the positions N-1 and C-6 can be determined by an appropriate choice of the aldehyde and amine. Various substituents can easily be introduced at the C-3 position via addition/elimination reactions on the sensitive imidoyl chloride moiety [24]. Upon reaction with bi-functional reagent, an adequately AT-protected 2(lH)-pyrazinone was elaborated into C-nucleoside analogues (Scheme 8). The desired skeleton and functionalities were obtained by oxidation-cyclization reaction followed by photochemical removal of the protective o-nitrobenzyl group [25]. 

OS 78] [R 4a] [P 58] The Wittig reactions of five aldehydes with 2-nitrobenzyl-triphenylphosphonium bromide were investigated also at a 1 1 stoichiometric ratio [13]. Using optimized reaction conditions, improved yields were found for four of the five aldehydes. 

The first clue to the existence of the SrnI mechanism came from product studies both in aliphatic and aromatic cases. It was noticed that in the reaction of benzyl and substituted benzyl chlorides with the 2-nitropropane anion, oxygen alkylation, yielding the oxime and then the aldehyde, occurs exclusively in the case of benzyl chloride and 3-nitrobenzyl chloride, whereas, with 4-nitrobenzyl chloride, the yield of aldehyde is only 6% and the carbon-alkylated (104) product is obtained in 92% yield (Kornblum, 1975). This was interpreted as the result of a competition between 8, 2 (O-alkylation) and S l (C-alkylation) reactions. In the aromatic case, it was observed that the reaction of 5- and 6-halopseudocumenes with KNHj in liquid ammonia (Kim and Bunnett, 1970) forms the 5- and 6-pseudocumi-dines in a ratio which is the same whether the starting compound is the 5- or 6-isomer in the case of the chloro- and bromo-derivatives, as expected from an aryne mechanism (Scheme 9), whereas much more non-rearranged... 

Experiments in deoxygenated ethanol solution in the dark showed that, by stirring, 4-nitrobenz-aldehyde is obtained in 60% yield, accompanied by 13% 2-(4-nitrobenzyl)-2-nitropropane. Under the same conditions, but with sonication, the yields are 23% of 4-nitrobenzaldehyde and 48% of 2-(4-nitrobenzyl)-2-nitropropane (Einhorn et al. 1990). The importance of this result consists in the following conclusion The ultrasonic irradiation has a marked influence on the relative rates of the competing reactions and stimnlates just the ion-radical one. 

Reductive ring closure of l-(2-nitrobenzyl)-2-pyrrole carbaldehyde 200 results in pyrrolo[2,l-c][l,4]benzodiazepine 201 (Scheme 42 (1999BMCL1737)). On the other hand, oxo derivative 203 can be synthesized starting from aldehyde 200 through a nitrile formation/cyclizations multistep sequence. The alternate synthetic strategy included reduction of the intermediate acid (R = H) or ester (R = Et) 205 followed by CDI or thermal cyclization (1992JHC1005). 

Protection of aldehydes and ketones.1 Bis-o-nitrobenzyl acetals or ketals are removable in 85-95% yield on irradiation at 350 nm in benzene. The acetals or ketals are easily prepared from 1 by an exchange reaction using 2,2-dimethoxy-propane (1, 268-269) catalyzed by an arenesulfonic acid. In the case of hindered ketones (17-keto steroids), the glycol o-N02C6H4CH(OH)CH2OH (2) can be used. 

The aldehydes 3 were synthesized either by Vilsmeyer formyladon of 2 or by reaction of 4-fluorobenzaldehyde with a secondary amine (20). The stilbenes 4 were formed from the corresponding 4-dialkylamino-benzaldehydes either by the Homer-Emmons reaction with 4-nitrobenzyl-(diethyl)phosphonate (prepared by the Arbuzov reaction of a-bromo-4-nitrotoluene) or with 4-methylsulfonylbenzyl(diethyl)phosphonate (prepared in three steps from 4-methylthiobenzylaicohol) (21). A few nitrostilbene compounds were synthesized by heating aldehyde 3 with 4-nitrophenylacetic acid in the presence of piperidine. 

Discussion Catalyst 52 is prepared from Boc-(L)-ter -leucine in five steps, with a 75% overall yield [41]. Details of imine and phosphite preparation are also provided by Jacobsen and co-workers [81]. The hydrophosphonylation reactions as reported by Jacobsen can be carried out without any special precautions, in unpurified commercial diethyl ether (Et20) and under an ambient atmosphere. A reduction in temperature was shown to have a beneficial effect on product enantiopurities, but with a decrease in reaction rates. Unbranched aliphatic aldehydes were incompatible with the reaction conditions as reported, due to their rapid decomposition prior to phosphonylation. Although phosphite ester groups that are more electron-withdrawing than o-nitrobenzyl significantly increase the overall reaction rates, products are obtained with diminished optical purities, possibly due to a retro-addition pathway. 

Kaufmann and Hof3 (p. 181) had subjected m-nitr V aldehyde to reduction in alkaline solution, but they til observe the occurrence of the mixed azo-compound they only the azo-alcohol and the azo-acid, and explained th yield, of the former by the behavior of the m-nitrobenzyl I towards alkalies, as shown in the equation ... 

Another aminomethyl PS resin supported o-nitrobenzyl photolabile hnker 1.23 (80) has been employed for the synthesis of heterocycles such as thiazohdinones. Attachment to the resin is through an acid or aldehyde group and photolytic cleavage is performed in 5% dimethyl sulfoxide (DMSO)-aqueous buffer to facilitate the biological testing of the final compound. A photolabile hydroxyl linker 1.24 (81), again supported on aminomethyl PS resin, has been used to synthesize carbohydrate and peptide derivatives in SP. The easily prepared diol linker 1.25 (82) allowed the attachment of aldehydes as acetals and their photo induced release using standard conditions. 

There is an interesting limitation to the method 4-nitrobenzyl chloride gives only 1% of the aldehyde, the major product being the result of single-electron transfer and radical coupling (equation 21). ... 

The development of a new synthesis of 1-hydroxyindoles 131, via a lead-promoted intramolecular reductive cyclization of the o-nitrobenzyl ketones (or aldehydes) 132 in the presence of tetraethylammonium formate (TEAF), offers a new useful route to this interesting class of compounds <03JOC9865>. 

The reaction is most useful for the preparation of olefinic, halo, and nitro alcohols from the corresponding substituted aldehydes and ketones. These substituents ate very often affected by other reduction procedures. Excellent directions are found in the preparations of crotyl alcohol (60%), l-bromo-5-hexanol (64%), l-chloco-4-pentanol (76%), /S,/S,/S-trichloroethyl alcohol (84%), methyl-p-chlorophenylcarbinol (81%), and o-nitrobenzyl alcohol (90%). The reaction has also been used in the preparation of certain tetralols and decalols as well as 9-fluo-renylcarbinol (50%). The thiophene and furan nuclei are not reduced. 

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