Nitro compounds, alkylation preparation

Aliphatic nitro compounds. These are isomeric with the alkyl nitrites and may be prepared from the alkyl halide and silver nitrite, for example C,H,aBr + AgNOj — C Hj NO + AgBr... 

I itro-DisplacementPolymerization. The facile nucleophilic displacement of a nitro group on a phthalimide by an oxyanion has been used to prepare polyetherimides by heating bisphenoxides with bisnitrophthalimides (91). For example with 4,4 -dinitro monomers, a polymer with the Ultem backbone is prepared as follows (92). Because of the high reactivity of the nitro phthalimides, the polymerkation can be carried out at temperatures below 75°C. Relative reactivities are nitro compounds over halogens, Ai-aryl imides over A/-alkyl imides, and 3-substituents over 4-substituents. Solvents are usually dipolar aprotic Hquids such as dimethyl sulfoxide, and sometimes an aromatic Hquid is used, in addition. 

The two major methods of preparation are the cycloaddition of nitrile oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamines. Additional methods include reaction of /3-haloketones and hydroxylamine, the reaction of ylides with nitrile oxides by activation of alkyl nitro compounds from isoxazoline AT-oxides (methoxides, etc.) and miscellaneous syntheses (62HC(i7)i). 

Of the four possible oxazolopyridines, two have been studied with respect to quatemization reactions. Frazer and Tittensor prepared 2-alkyl- and 2-aryl-oxazolo[4,5-c]pyridines (105 Y = H) and converted them into methiodides, the structures of which have not been determined. Subsequently Takahashi et al. prepared the corresponding 5-methyl (105 Y = Me) and 2-methyl-5-nitro compounds and... 

Trruii -fused bicychc compounds are prepared by the double Michael lompounds the nitro group is further alkylated by the radical reacdoii fEq. 7.81. ... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Tertiary alkyl primary amines can be oxidized to nitro compounds in excellent yields A ith KMn04. This type of nitro compound is not easily prepared in other ways. 

The reaction of alkyl halides with metal nitrites is one of the most important methods for the preparation of nitroalkanes. As a metal nitrite, silver nitrite (Victor-Meyer reaction), potassium nitrite, or sodium nitrite (Kornblum reaction) have been frequently used. The products are usually a mixture of nitroalkanes and alkyl nitrites, which are readily separated by distillation (Eq. 2.47). The synthesis of nitro compounds by this process is well documented in the reviews, and some typical cases are listed in Table 2.3.92a Primary and secondary alkyl iodides and bromides as well as sulfonate esters give the corresponding nitro compounds in 50-70% yields on treatment with NaN02 in DMF or DMSO. Some of them are described precisely in vol 4 of Organic Synthesis. For example, 1,4-dinitrobutane is prepared in 41 -46% yield by the reaction of 1,4-diiodobutane with silver nitrite in diethyl ether.92b 1-Nitrooctane is prepared by the reaction with silver nitrite in 75-80% yield. The reaction of silver nitrite with secondary halides gives yields of nitroalkanes of about 15%, whereas with tertiary halides the yields are 0-5%.92c Ethyl a-nitrobutyrate is prepared by the reaction of ethyl a-bromobutyrate in 68-75% yield with sodium nitrite in DMF.92d Sodium nitrite is considerably more soluble in DMSO than in DMF as a consequence, with DMSO, much more concentrated solutions can be employed and this makes shorter reaction times possible.926... 

A number of nitro compounds used in natural product synthesis have been prepared by the nitration of alkyl halides. Some recent examples are summarized in Table 2.4. 

Couplings of nitroalkyl radicals with nucleophiles such as CN-, N, N02, and other nitrogen nucleophiles provides a useful method for the preparation of nitro compounds with such groups at the a-position.49 65 The alkylation of nitromethane with trialkylborane is possible by electrolysis, in which alkyl radicals may be involved (Eq. 5.46).66... 

The hydrogenation in the presence of Pd/C is also effective for the conversion of nitro compounds to amines.94 The Michael addition of nitromethane to 2-alkenoic esters followed by catalytic hydrogenation using 10% Pd/C in acetic acid and hydrolysis is a convenient method for the preparation of 3-alkyl-4-aminobutanoic acids, which are important y-amino acids for biological study (Eq. 6.48).94b The reduction can be carried out at room temperature and atmospheric pressure. 

X,P-Dehydro-a-amino acids are prepared by elimination of HN02 from P-nitro-a-amino acids, which are prepared by reaction of a-bromoglycine derivatives with alkyl nitronates (see Eq. 7.135).181 This process is a new type of the Michael addition of nitro compounds followed by elimination of HNOz. Such unusual amino acids are interesting as enzyme inhibitors.182... 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

Organic nitro compounds, RNO2, can be reduced to amines. The R may be either alkyl or aryl. Aromatic nitro compounds are easy to prepare and reduce. Their preparation utilizes a mixture of nitric acid and sulfuric acid to nitrate the aromatic ring. (However, multiple nitrations may occur, potentially causing problems.) The nitro group can be reduced with a... 

Tertiary alkyl primary amines can be oxidized to nitro compounds in excellent yields with KMn04.39S This type of nitro compound is not easily prepared in other ways. All classes of primary amine (including primary, secondary, and tertiary alkyl as well as aryl) are oxidized to nitro compounds in high yields with dimethyldioxirane.399 Other reagents that oxidize various types of primary amines to nitro compounds are dry ozone,4,111 various peracids,401 including peracetic and peroxytrifluoroacetic acids, f-butyl hydroperoxide in the presence of certain molybdenum and vanadium compounds,402 F7-H20-MeCN,41123 and sodium perborate.403... 

Nitro compounds. Aliphatic nitro compounds are acidic. They are freed from alcohols or alkyl halides by standing for a day with concentrated sulphuric acid, then washed with water, dried with magnesium sulphate followed by calcium sulphate and distilled. The principal impurities are isomeric or homologous nitro compounds. In cases where the nitro compound was originally prepared by vapour phase nitration of the aliphatic hydrocarbon, fractional distillation should separate the nitro compound from the corresponding hydrocarbon. Fractional crystallisation is more effective than fractional distillation if the melting point of the compound is not too low. 

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