Nitro monoalkylation

Monoalkylation of Af-tosylallylamine 10 with dibromoalkane 101 proceeded in 60-90% yield (Eq. 10 see also Scheme 3 and Eq. 2) [17]. The bromoalkyl-amines 102 were converted to nitro compounds 103. In situ transformation of 103 into nitrile oxides led to spontaneous cycloaddition with formation of isox-azolines fused to 5-, 6-, and 7-membered ring heterocycles 104 a-c. Under very high dilution conditions, 103 d was converted to 104 d, an isoxazoline fused to an 8-membered azocine, in low (10%) yield. 

Nitration of ketones or enol ethers provides a useful method for the preparation of a-nitro ketones. Direct nitration of ketones with HN03 suffers from the formation of a variety of oxidative by-products. Alternatively, the conversion of ketones into their enolates, enol acetates, or enol ethers, followed by nitration with conventional nitrating agents such as acyl nitrates, gives a-nitro ketones (see Ref. 79, a 1980 review). The nitration of enol acetates of alkylated cyclohexanones with concentrated nitric acid in acetic anhydride at 15-22 °C leads to mixtures of cis- and rrans-substituted 2-nitrocyclohexanones in 75-92% yield. 4-Monoalkylated acetoxy-cyclohexanes give mainly m-compounds, and 3-monoalkylated ones yield fra/w-compounds (Eq. 2.40).80... 

The phosphate method has not been synthetically useful for alkylation of anilines of low basicity such as -nitro- or p-trifluoroaniline. Only monoalkylation occurs in introducing branched-chain alkyl groups such as isopropyl. Use of this method for alkylation of aliphatic amines has not been reported. 

Nitration of triazole and its C-monoalkyl derivatives fails. Aryltriazoles are nitrated on the aryl ring in preference to the triazole, but 3-p-nitrophenyltriazole in which each ring is deactivated gives l-nitro-3-j7-nitrophenyltriazole which rearranges at 120°C to 3-nitro-5-p-nitrophenyltriazole <72CC37>. 

Die Herstellung von Monoalkyl- bzw. Monoarylestern aus den gut zuganglichen Phos-phorsaure-alkyl(aryl)ester-(2-chlormethyl-4-nitro-phenylestern) gelingt durch Erwar-men in Pyridin/Wasser auf 90° (83-94%)2 ... 

The dianions of /S-enamino ketones react with a wide range of electrophiles such as alkyl halides, oxiranes, nitriles, esters, aldehydes and ketones37. Dalpozzo and coworkers reported the generation of the dianion derived from /S-enamino ketones with lithium 2,2,6,6-tetramethylpiperidide and the reaction of the dianion with nitroalkene (Scheme 24)38. The dianion underwent exclusive alkylation at the y-carbon atom to give the monoalkylated product in high yield. This reaction is useful for the introduction of a nitro group into a ketone side chain. 

Figure 10.25 Twenty-nine specific toxicophores for mutagenicity as identified by Kazius el al. (Kazius, J-, et al. Derivation and validation of toxicophores for mutagenicity prediction. J. Med. Chem. 2005, 48, 312-320.) (A) Specific aromatic nitro, (B) specific aromatic amine, (C) aromatic nitroso, (D) alkyl nitrite, (E) nitrosamine, (F) epoxide, (G) aziridine, (H) azide, (I) diazo, (J) triazene, (K) aromatic azo, (L) unsubstituted heteroatom-bonded heteroatom, (M) aryl hydroxylamine, (N) alkyl halide, (O) acyl halide, (P) N- or 5-mustard, (Q) polycyclic aromatics, (R) bay-region, (S) K-region, (T) sulphonate-bonded C, (U) unsaturated aldehyde, (V) alkyl A-nitro, (W) diazonium, (X) p-propiolactone, (Y) unsubstituted a,p unsaturated alkoxy, (Z) l-aryl-2-monoalkyl hydrazine, (AA) aromatic methylamine, (AB) aryl hydroxylamine ester, and (AC) polycyclic planar system.

Alkylation of symmetrical ketones or of ketones that can enolize in one direction only can, of course, give just one mono-C-alkylated product. With unsynametrical ketones, however, two different monoalkylated products may be formed by way of the two structurally isomeric enolate anions. If one of the isomeric enolate anions is stabilized by conjugation with another group, such as cyano, nitro or a carbonyl group, then only this stabilized anion is formed and alkylation takes place at the position activated by both groups. Even a phenyl or an alkenyl group provide sufficient stabilization of the resulting anion to direct substitution into the adjacent... 

Different y- and d-aminofrmctionalized ethers, amines and silanes 169 are obtained from aUcenes 168. Branched derivative is the main product obtained when X=OR, NR. The alkylation of the primary amines leading to secondary or tertiary amines can be controlled by the alkene/amine ratio [100]. Nitro derivatives can be used instead of amines, since they are rednced to amines in the reaction conditions [101]. Selective monoalkylation or dialkylation of nitro compounds is achieved depending on the alkene/nitro compound ratio. 

Conjugation of the nitro-group by attachment to an ethylenic double bond leads to a fall in both frequencies similar to that shown by the carbonyl absorption. Shechter and Sheppard [27], for example, find that 2-methyl-l-nitropropene absorbs at 1515 cm and 1350cm", whereas 2-methyl-3-nitropropene absorbs at 1555 cm and 1366 cm . This has been confirmed also by Brown [25], who finds the ranges 1524 4cm and 1353 6 cm" for monoalkyl nitroethylenes and slightly lower values of 1515 4 cm" and 1346 9 cm" for di- and tri-alkylnitroethylenes. 

Treatment of primary aromatic amines with Ph3PBr2 to produce the imino-phosphorane followed by addition of an alkyl iodide provides a convenient monoalkylation procedure.The reagent system BusP-CCU-KCN-lS-crown-6 effects a simple one-pot conversion of primary alcohols to nitriles. Finally, PI3 deoxygenates sulphoxides, selenoxides, aldehyde oximes, and nitro-alkanes, and deprotects acetals and ketals. ... 

Cyclopropanecarboxylic esters have been prepared, in 75—86 % yield, by intramolecular alkylation of 4-chloroalkyl esters, using phase-transfer catalysis. Monoalkylation of nitro-alkenes by acrylic esters occurs in a controlled manner if a two-phase system is used, to give products of Michael addition in 45—65 % yield for five examples. An interesting variant on this reaction involves the generation of the a-nitro-carbanion by conjugate reduction of a nitroalkene with sodium borohydride followed by its conjugate addition to methyl acrylate yields of 62—95% are reported for five cases (Scheme 39). ... 

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