Nitros amines synthesis

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). 

Three derivatives of 3-aminodibenzothiophene, 110a, 110b, and 110c, have been nitrated, and in each case substitution occurred in the 4-position. Hydrolysis of the products yielded 3-amino-4-nitro-dibenzothiophene, which was different from the previous two nitro-amines and which formed an imidazole different from both 104 and 109. Deamination of this nitroamine via diazotization gave a small amount of 4-nitrodibenzothiophene. An alternative synthesis of the 4-nitro compound is described later. The spectroscopic techniques used above by Sawicki were later extended to determine the positions of substitution in dibenzoselenophene, in this case by comparison with the above-established derivatives of dibenzothiophene. - ... 

Reactions of the Nitroso Group. Up until recently, the chemistry of N-nitrosamines was restricted to the reaction involving the nitroso group. It was not until the usefulness of N-nitros-amines in synthesis [concept of "Umpolung (3.)] was demonstrated, that the long-known denitrosation of N-nitrosamines became impor-... 

This elegant synthesis uses some of the methods of amine synthesis from this chapter and looks forward to the next chapter on protecting groups as well as later discussion of nitro group chemistry. 

Aqueous reductions are useful for amine synthesis. Organic reducing agents (N H or formic acid) reduce amides or imines . Active metals in acid reduce nitro groups . Reduction of Ph3PNBr with I ... 

Figure 1. Reductive amination of nitro derivatives-synthesis of non-natural amino acid precursors.

Nitroarenes and nitriles could also be employed as amine precursors. In 2010, Li and co-workers reported a ruthenium complex-catalyzed synthesis of tertiary amines by A -alkylation of nitroarenes with alcohols (Eq. 14) [87], In this method, large excess amounts of the alcohols (mostly 7.5 equiv.) are necessary to reduce the nitroarenes to anilines prior to A -alkylation. In 2011, Shi and co-workers also developed an amination reaction for secondary amine synthesis from nitro or nitrile compounds (Eq. 15) [88]. In the same year, Deng and co-workers reported a ruthenium-catalyzed method for tertiary-amine synthesis from nitriles and primary alcohols [89]. In 2013, Beller and co-workers reported another A -alkylation reaction of nitrile compounds with secondary alcohols [90]. 

Cui X, Shi F, Deng Y et al (2011) Ruthenium-catalyzed nitro and nitrile compounds coupling with alcohols alternative route for Ai-substituted amine synthesis. Chem-Eur J 17(9) 2587-2591... 

Sc(OTf)3 (4 mol%)-catalyzed addition of 1-trimethylsilyl nitropropanate to aryl and alkylimines was described [109]. The use of N-(4-methoxyphenyl)imines gave superior yields and/or diastereoselectivities of P-nitro amines in most cases (72-99% yield, antijsyn = 5/3-9/1). The products could be reduced to 1,2-diamines by samarium diiodide reduction, formation of the cyclic urea and cleavage of the 4-methoxyphenyl group with ceric ammonium nitrate (CAN). This methodology was later employed for the synthesis of pseudo-C2-symmetric triamines as candidates for human immunodeficiency virus (HIV) protease inhibition [110]. 

Scheme 3.41 Synthesis of nitro-amine biphenyl compound 95.

The preparation of amines by the methods described m this section involves the prior synthesis and isolation of some reducible material that has a carbon-nitrogen bond an azide a nitrile a nitro substituted arene or an amide The following section describes a method that combines the two steps of carbon-nitrogen bond formation and reduction into a single operation Like the reduction of amides it offers the possibility of prepar mg primary secondary or tertiary amines by proper choice of starting materials... 

Furalazine, Acetylfuratrizine, Panfuran-S. Heating nitrovin in butanol or dimethylformamide at 100—130°C affords furalazine, 6-[2-(5-nitro-2-furanyl)ethenyl]-l,2,4-triazine-3-amine (34). An improved synthesis originates with 5-nitro-2-furancarboxaldehyde and acetone, proceeds through 4-(5-nitro-2-furanyl)-3-buten-2-one followed by a selenium dioxide oxidation to the pymvaldehyde hydrate, and subsequent reaction with aininoguariidine (35). Furalazine, acetylfuratrizine (36), and the A[-A/-bis(hydroxymethyl) derivative, Panfuran-S, formed from the parent compound and formaldehyde (37), are systemic antibacterial agents. 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

Purines, N-alkyl-N-phenyl-synthesis, 5, 576 Purines, alkylthio-hydrolysis, 5, 560 Mannich reaction, 5, 536 Michael addition reactions, 5, 536 Purines, S-alkylthio-hydrolysis, 5, 560 Purines, amino-alkylation, 5, 530, 551 IR spectra, 5, 518 reactions, 5, 551-553 with diazonium ions, 5, 538 reduction, 5, 541 UV spectra, 5, 517 Purines, N-amino-synthesis, 5, 595 Purines, aminohydroxy-hydrogenation, 5, 555 reactions, 5, 555 Purines, aminooxo-reactions, 5, 557 thiation, 5, 557 Purines, bromo-synthesis, 5, 557 Purines, chloro-synthesis, 5, 573 Purines, cyano-reactions, 5, 550 Purines, dialkoxy-rearrangement, 5, 558 Purines, diazoreactions, 5, 96 Purines, dioxo-alkylation, 5, 532 Purines, N-glycosyl-, 5, 536 Purines, halo-N-alkylation, 5, 529 hydrogenolysis, 5, 562 reactions, 5, 561-562, 564 with alkoxides, 5, 563 synthesis, 5, 556 Purines, hydrazino-reactions, 5, 553 Purines, hydroxyamino-reactions, 5, 556 Purines, 8-lithiotrimethylsilyl-nucleosides alkylation, 5, 537 Purines, N-methyl-magnetic circular dichroism, 5, 523 Purines, methylthio-bromination, 5, 559 Purines, nitro-reactions, 5, 550, 551 Purines, oxo-alkylation, 5, 532 amination, 5, 557 dipole moments, 5, 522 H NMR, 5, 512 pJfa, 5, 524 reactions, 5, 556-557 with diazonium ions, 5, 538 reduction, 5, 541 thiation, 5, 557 Purines, oxohydro-IR spectra, 5, 518 Purines, selenoxo-synthesis, 5, 597 Purines, thio-acylation, 5, 559 alkylation, 5, 559 Purines, thioxo-acetylation, 5, 559... 

Pyrimidin-2-amine, 4-ethyI-5-(2 -hydroxy-4 -nitrophenyI)-6-methyl-synthesis, 3, 121 Pyrimidin-2-amine, 4-methyl-basic pXj, 3, 61 Pyrimidin-2-amine, N-methyl-hydrolysis, 3, 84 synthesis, 3, 135 Pyrimidin-2-amine, 5-nitro-basic pXj, 3, 61 hydrolysis, 3, 84 Pyrimidin-2-amine, 4-phenyl-synthesis, 3, 109 Pyrimidin-2-amine, 5-phenyl-nitration, 3, 78... 

Pyrimidin-4-amine, 5-nitro-2-styryI-reduction, 3, 88 Pyrimidin-4-amine, 2-phenyl-hydrolysis, 3, 84 Pyrimidin-4-amine, 5-phenyI-synthesis, 3, 116 Pyrimidin-4-amine, triphenyl-synthesis, 3, 119... 

Nickel compounds Hydrogenations (e.g. Raney nickel) Conversion of synthesis gas to methane Reduction of organo nitro compounds to amines Carcinogenic (nickel subsulphide). Skin sensitization... 

A heterocyclic ring may be used in place of one of the benzene rings without loss of biologic activity. The first step in the synthesis of such an agent starts by Friedel-Crafts-like acylation rather than displacement. Thus, reaction of sulfenyl chloride, 222, with 2-aminothiazole (223) in the presence of acetic anhydride affords the sulfide, 224. The amine is then protected as the amide (225). Oxidation with hydrogen peroxide leads to the corresponding sulfone (226) hydrolysis followed by reduction of the nitro group then affords thiazosulfone (227). ... 

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