Nitro compounds with aldehydes

Conjugated nkro ilkenes are isomerized to illylic nitro compounds under basic conditions Reactions of a,fi-unsarurated nitro compounds with aldehydes under basic conditions lead directly to y, 5-unsaturated fi-nitro alcohols fEq 3 24 "This reaction is very useful for preparing illyhc nitro compounds... 

A nitro alcohol is formed when an ahphatic nitro compound with a hydrogen atom on the nitro-bearing carbon atom reacts with an aldehyde in the presence of a base. Many such compounds have been synthesized, but only those formed by the condensation of formaldehyde (qv) and the lower nitroparaffins (qv) are marketed commercially. The condensation may occur one to three times, depending on the number of hydrogen atoms on the nitro-substituted carbon (R and R = H or alkyl), and yield nitro alcohols with one to three hydroxyl groups. 

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-... 

The conversion of nitro compounds to aldehydes or ketones has been carried out with better yields and fewer side reactions by several alternative methods. Among these are treatment of the nitro compound with tin complexes and NaHS03, ... 

Reactions of nitro compounds with chiral imines have only recently been described. Either chiral 1-phenylethylamine (auxiliary) or the glyceraldehyde acetonide aldehyde was used as the chiral precursors of the imines 66 and 68, which reacted with 3-mesyloxynitropropane to give the 3-nitropyrrolidines dl)-67 and 69, respectively, with good diastereoselectivity. In fact, both products were obtained (almost) exclusively as trans diastereomers with high level of asymmetric induction, but the configurations of the newly formed stereocenters were not determined [44] (Scheme 13). N-Boc imines can be formed... 

The conversion of primary or secondary nitro compounds into aldehydes or ketones is normally accomplished by use of the Nef reaction, which is one of the most important transformations of nitro compounds. Various methods have been introduced forthis transformation (1) treatment of nitronates with acid, (2) oxidation of nitronates, and (3) reduction of nitroalkenes. Although a comprehensive review is available,3 important procedures and improved methods published after this review are presented in this chapter. The Nef reaction after the nitro-aldol (Henry reaction), Michael addition, or Diels-Alder reaction using nitroalkanes or nitroalkenes has been used extensively in organic synthesis of various substrates, including complicated natural products. Some of them are presented in this chapter other examples are presented in the chapters discussing the Henry reaction (Chapter 3), Michael addition (Chapter 4), and Diels-Alder reaction (Chapter 8). 

The Nef reaction of primary nitro compounds gives aldehydes or carboxylic acids, depending on the reaction conditions. Each transformation provides an important tool in organic synthesis. Primary nitro compounds are converted into carboxylic acids with concentrated mineral acids.22 Because such harsh conditions also lead to side reactions, a milder method is required in organic synthesis. Basic phosphate-buffered KMn04 rapidly converts primary nitroalkanes into carboxylic acids in 90-99% yield (Eq. 6.13).23... 

The reaction of tertiary nitro compounds with the sodium salt of nitromethane followed by the Nef reaction provides a good method forthe preparation of quaternary aldehydes (Eq. 7.10).8 Because the nitromethyl group can be transformed into other groups such as CN, C02H, or CH2NH2, the SRN I reaction of tertiary nitro compounds with the anion of nitromethane is a synthetically useful method (Kornblum reaction).10 For example, the nitromethylation of tertiary nitro compounds has been applied for preparing starting materials for cascade polymers (Eq. 7.11).9... 

In 1982, a new reaction was reported by Tamura and Ono namely, allylic nitro compounds undergo replacement of the nitro group by various nucleophiles in the presence of a palladium (0) catalyst.17a b 18a b The details of these reactions are discussed in Ref. 2b here, only some typical examples are presented. Carbon, sulfur, nitrogen, and phosphorous centered nucleophiles replace the nitro groups at the allylic positions. The reaction of allylic nitro compounds with triphenylphosphine is applied to the highly stereoselective olefination of aldehydes (Eqs. 7.15-7.18).19... 

The regiochemical control of Pd-catalyzed hydride transfer reaction is much more effective than that of the radical denitration, as shown in Eq. 7.98. The base-catalyzed reaction of nitroolefins with aldehydes followed by denitration provides a new synthetic method of homoallyl alcohols (Eq. 7.99).140 Exomethylene compounds are obtained by denitration of cyclic allylic nitro compounds with Pd(0), HC02H and Et3N (Eq. 7.100).140b... 

Nef reaction.4 Nitro compounds, primary or secondary, are converted to tri-alkylsilyl nitronates in greater than 90% yield by reaction with a trialkylsilyl chloride and DBU in CH2C12. The silyl nitronates derived from secondary nitro compounds are oxidized by C1QH4C03H at 25° to ketones in high yield. This sequence is not useful for conversion of primary nitro compounds to aldehydes. 

In a manner similar to that of l-tosyl-4,6-dinitroindoline (see Scheme 28, Section 2.2.1), 4,6-dinitrobenzofuran undergoes condensation with salicylic aldehyde under basic conditions followed by nitro group substitution/cycliza-tion to afford a mono nitro compound with peri-fusion of the benzofuran ring in 68% yield (2005CHE796). 

The connection of the aromatic mono-, di- and tri-nitro compounds with phytochemical reduction follows from their activating action in alcoholic fermentation, known for a quarter century.The same applies equally to the excellent activating effect of cinnamic aldehyde its behavior during phytochemical eduction is described on pages 79 and 105. 

Quaternary aldehydes. Tertiary nitro comounds (1) can be converted to primary nitro compounds with a quaternary center (2) by reaction with the sodium salt of nitromethane in the presence of sodium hydride in DMSO (equation I).1... 

Several methods have been used to convert primary nitro compounds into aldehydes, but the most effective one in the present case is oxidation of the corresponding sodium nitronate with potassium permanganate (1, 950-951). 

Tertiary arylamines were prepared in good yields by hydrogenation of an alcoholic solution of a nitro compound and an aldehyde over Raney Ni in the presence of triethy-lamine hydrochloride or, better, over platinum oxide in the presence of acetic acid (eq. 6.22).48 Base metal and platinum metal sulfides are also effective to the reductive alkylation of nitro compounds with ketones36,37 as in an example shown in eq. 6.23. 

Although discovered in the eariy 19(X)s, the oxidation of nitro compounds with potassium permanganate has become a truly useful reaction only within the last 23 years. An alkoxide base is used to form the nitronate salt, and aqueous potassium permanganate gives the oxidized product in excellent yield. Even aldehydes can be obtained as in equation (9) without loss of the pivaloyl group. Cetyltri-... 

Sodium methoxide on silica gel (2 mol equiv. Na per g reagent), is an excellent reagent for effecting the Nef reaction by converting nitro compounds to aldehydes and ketones. The reactions are run either at room temperature or at 80 C, for a short reaction time. The success of these reactions depends on the neutralization of the normally weakly acidic silica gel by treatment with methoxide in methanol, followed by evaporation to dryness and activation by heating to 400 C. The nitro substrate is then impregnated onto this methoxide-doped silica gel to effect reaction. 

When aliphatic nitro compounds are used instead of aldehydes or ketones, no reduction occurs, and the reaction has been referred to as a Tollens reaction (see 16-43). However, the classical condensation of an aliphatic nitro compound with an aldehyde or ketone is usually called the Henry reaction or the Kamlet reaction, and is essentially a nitro aldol reaction. A variety of conditions have been reported, including the use of a silica catalyst, Mg—A1 hydrotalcite, a tetraalkylam-monium hydroxide,proazaphosphatranes, " or an ionic liquid.A solvent free Henry reaction was reported in which a nitroalkane and an aldehyde were reacted on KOH powder. Potassium phosphate has been used with nitromethane and aryl aldehydes. The Henry reaction has been done using ZnEt2 and 20%... 

Nitrene can be generated by Pd-catalyzed deoxygenation of organic nitro compounds with CO. Carbonylation of nitroenamine 226, derived from 2-nitroaniline and a-substituted aldehyde, was carried out using Pd(dba)2 and dppb. A mixture of 1,2-dihydroquinoxaline 227 and 3,4-dihydroquinoxaline 228 was obtained via sequential reactions of carbon monoxide insertion, heterocyclization, and A-alkylation followed by dealkylation [115]. 

Although interaction of an aromatic aldehyde and a primary nitro compound with a primary amine as catalyst leads to the nitro olefin in one step, this need not be the case with other catalysts. 

Lasers. Chelates of europium with some aromatic nitro compounds with phenolic and aldehydic function can be used to produce laser beams [137]. 

In this approach, conjugate addition of the anion from an isocyanoacetate to an a,/3-unsaturated nitro compound with eventual loss of nitrous acid, produces 5-unsubstituted pyrrole-2-esters. This route has become very popular the examplebelow shows a mechanistic sequence which can be seen to parallel that in the van Leusen synthesis. The most useful route to the a,/ -unsaturated nitro compound involves the base-catalysed condensation of an aldehyde with a nitroalkane giving an a-hydroxy nitroalkane it can alternatively be generated in situ, in the presence of the isonitrile, using diazabicycloundecane as base on the O-acetate of the a-hydroxy nitroalkane (for an example see section 13.18.3.3). 

RCH2.NO2 - RC=N. This conversion usually has been conducted via a Nef reaction to an aldehyde followed by formation and dehydration of an oxime. The transformation can be accomplished in one step by reaction of the primary nitro compound with PCI3 and pyridine (40-75% yield). This method can also be used to convert allylic nitro compounds into a,)3-unsaturated nitriles and to prepare aldehyde or ketone cyanohydrin acetates. 

All primary acid hydrazides yield readily crystal line compounds with aldehydes and ketones. Nitro... 

Hydrogenation of Carbon-Carbon Multiple Bonds. There are a number of ruthenium complexes that can catalyze hydrogenation of various substrates, either through reduction with molecular hydrogen, or transfer reactions from a hydrogen donor. Generally, the available substrates for hydrogenation include the double bonds present in nitro compounds, alkenes, aldehydes, ketones, and other carboxylic acid derivatives (4). 

For the identity of the compounds see Scheme 6. Experimental conditions Substrate/catalyst = 43, Pco = 50 bar, T = 220 °C. 25 = o-phenylenediamine. ) Calculated with respect to converted nitro compoimd. ) Reaction carried out after adding fresh nitro compound and aldehyde to the solution of run 1. ) Reaction carried out after adding fresh nitro compound and aldehyde to the solution of ran 2. ) Substrate/catalyst ratio = 100. Without nitro comiMund and with HjO (HjO/aldehyde ratio = 2). ) Without aldehyde and with water (IhO/nitro compound ratio = 2). ) Monohydrated glyoxal C2H202-H20. 

The reaction of nitroaniline and the aldehyde gives a stoichiometric amount of water (or hydrogen, since it is known that Ru3(CO)n catalyses the WGSR, e.g. [51]). The presence of water accounts for the presence of several by-products formed in small amounts [48]. At the end of run 1, new nitro compound and aldehyde were added to the solution and a second catalytic cycle was carried out (Table 8, run 2), with results almost identical to those of run 1. The same results were also obtained with a third run (run 3). In spite of the presence of water, at the end of the reaction the catalyst was recovered as the usual mixture of Ru3(CO)i2 and Ru(CO)s and no trace of Ru-H bonds was detected by IR spectroscopy. The reaction gave complete conversion of the nitro compound even on lowering the reaction time to 1 h (run 4). Only for an half an hour... 

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