Esters nitro

It is frequently advisable in the routine examination of an ester, and before any derivatives are considered, to determine the saponification equivalent of the ester. In order to ensure that complete hydrolysis takes place in a comparatively short time, the quantitative saponi fication is conducted with a standardised alcoholic solution of caustic alkali—preferably potassium hydroxide since the potassium salts of organic acids are usuaUy more soluble than the sodium salts. A knowledge of the b.p. and the saponification equivalent of the unknown ester would provide the basis for a fairly accurate approximation of the size of the ester molecule. It must, however, be borne in mind that certain structures may effect the values of the equivalent thus aliphatic halo genated esters may consume alkali because of hydrolysis of part of the halogen during the determination, nitro esters may be reduced by the alkaline hydrolysis medium, etc. 

A number of selected aromatic nitro compounds are collected in Table IV,16A, It will be noted that a few nitro aromatic esters have been included in the Table. These are given here because the nitro group may be the first functional group to be identified aromatic nitro esters should be treated as other esters and hydrolysed for final identification. 

Active methylene or methine compounds, to which two EWGs such as carbonyl, alko.xycarbonyl, formyl, cyano, nitro, and sulfonyl groups are attached, react with butadiene smoothly and their acidic hydrogens are displaced with the 2,7-octadienyl group to give mono- and disubstituted compounds[59]. 3-Substituted 1,7-octadienes are obtained as minor products. The reaction is earned out with a /3-keto ester, /9-diketone, malonate, Q-formyl ketones, a-cyano and Q-nitro esters, cya noacetamide, and phenylsulfonylacetate. Di(octadienyl)malonate (61) obtained by this reaction is converted into an... 

One effective method for synthesis of tryptophan derivatives involves alkylation of formamido- or acetamido- malonate diesters by gramine[l,2]. Conversion to tryptophans is completed by hydrolysis and decarboxylation. These reactions were discussed in Chapter 12. An enolate of an a-nitro ester is an alternative nucleophile. The products can be converted to tryptophans by rcduction[3,4],... 

The toluene solution from the previous step was treated with an ethanol solution of NaOEt (0.1 mol in 100 ml) at O C. When about a quarter of the solution had been added a thick precipitate formed and ether (100 ml) was added to maintain a fluid slurry. The remainder of the NaOEt was added and the slurry was stirred overnight. The solid was collected and w ashed with ether. It was then mixed with ether (200 ml) and 2NHC1 (75 ml) and shaken in a separatory funnel until the solid dissolved. The ether layer was washed with 2NHHC1 (2 X 50ml) and water and dried over MgS04. The solution was decolorized with Magnesol and evaporated to give the a-nitro ester as a red oil. 

Nitrones or aci-nitro esters react with alkenes to give in some cases A/-substituted isoxazolidines and in others 2-isoxazolines. When the intermediate isoxazolidines were observed, a number of procedures transformed them into the 2-isoxazolines. Acrylonitrile and phenyl rzcf-nitrone esters produced an A/-methoxyisoxazolidine. Treatment with acid generated a 2-isoxazole while treatment with base generated an oxazine (Scheme 118) (68ZOR236). When an ethoxycarbonyl nitrone ester was reacted with alkenes, no intermediate isoxazolidine was observed, only A -isoxazolines. Other aci-mtro methyl esters used are shown in Scheme 118 and these generate IV-methoxyisoxazolidines or A -isoxazolines which can be further transformed (72MI41605). 

The trimethylsilyl group has been used to prepare stable aci-nitro esters and these react with alkenes to produce intermediate isoxazolidines which were readily converted into 2-isoxazolines (Scheme 119) (73ZOB1715, 74DOK109, 78ACS(B)ll8>. 

Other zinc reductions have been used extensively. Zinc dust in aqueous ammonium chloride is a standard reagent for the reductive cyclization of nitro esters to hydroxamic acids. These reactions are usually carried out at low temperatures (0°-10°) to avoid further reduction. Despite the fact that good yields can often be obtained, these reductions are highly capricious, depending on the quality of the zinc (impurities seem to improve the reaction) and other unknown factors. 

Earlier, the reduction of y-nitro esters with zinc and ammonium chloride had been shownto provide a suitable route to A-hydroxy 2-pyiTolidones, e.g., 42. Various catalytic hydrogenation procedures can also effect the same reductive cyclization. ... 

Perhaps the most reliable method for the reductive cyclization of a nitro ester to a hydroxamic acid is that which involves treatment with sodium horohydride in the presence of palladium on charcoal. Although under these conditions aromatic nitro compounds are reduced to amines, o-nitro esters such as 53, in which the ester group is suitably oriented with respect to the nitro group, give good yields of cyclic hydroxamic acids (54). Coutts and his co-... 

Side-chain functionalities react in an expected manner. For example, treatment of hydroxymethylfuroxan with HNO3 and H2SO4 gives the corresponding nitro ester (96IZV1782, 96RCB1692). 

In benzene or similar solvents, tris(triphenylphosphine)halogenorhodium(I) complexes, RhX[P(C6H5)3]3, are extremely efficient catalysts for the homogeneous hydrogenation of nonconjugated olefins and acetylenes at ambient temperature and pressures of 1 atmosphere (6). Functional groups (keto-, nitro-, ester, and so on) are not reduced under these conditions. 

Geminal dinitro compounds, " ct-nitro sulfones, " ct-nitro esters, or ct-nitro nitnles react v/ith anions derived from nitro ilkanes to give the Spj l products, as shovmin Eqs. 5.28, 5.29, 5.30 and 5.31, respecdvely fSecdon 7.1. ... 

Allylic carbonates are better electrophdes than allylic acetates for the pallathirm-catalyzed allylic alkylation. Reaction of Eq. 5.54 shows the selective allylic alkylation of ct-nitro ester v/ith allylic carbonates v/ithont affecting allylic acetates. ... 

PclCOi-cdidlyzed subsdnidoa reacdoa, a aovel, mild reducdoa of a-nitro ester to an amino acid ester withTiCU, and an improved procedure for nracil ring formadon. 

Barton and co workers have explored the aryladon of various nucleophiles inclndmg nitroalkanes using bismuth reagents Reacdon of 2-nitropropane v/ith triphenylbismnth carbonate gives 2-nitro-2-phenylpropane in 80% yield Recently, this aryladon has been used for the synthesis of unusual amino acids Aryladon of ct-nitro esters v/ith triphenylbismnth dichloride followed by redncdon gives unique ct-amino acids fEq 5 68 ... 

Hydrogen gas can be replaced by ammonium formate for the reduction of nitro compounds to amines. The ammonium formate method is efficient, and the rapid workup procedure by simple filtratkin makes it widely used for converting the NO to the NH. ° For example, ct-nitro esters are reduced to ct-amino esters in excellent yields on treatment v/ith HCO NH and PdAZ in methanol. ... 

In 1970, a new reacdon, the displacement of a nitro group from ct-nitro esters, ct-nitro nitnles, ct-nitro ketones, iind ct,ct-dinitro compounds by nitroalkiine salts, was described. These displacements, which are exemplified by the reacdon presented in Eq. 7.1, take place at room temperanire iind give excellent yields of pure products. The reacdon proceeds via a radiciil chain mechanism involving one electron-transfer processes as shovmin Scheme 7.1 the details of the mechanism are described in a review. ... 

Nitro- -ester 683 4-Nitro- -imidazolid 233 4-Nitro- -methylester 476, 501... 

Several cyditol derivatives of varying ring size, for example, (69)/(70), have been prepared based on an enzymatic aldolization as the initial step. Substrates carrying suitably installed C,H-acidic functional groups such as nitro, ester, phosphonate (or halogen) functionalities made use of facile intramolecular nucleophilic (or radical) cyclization reactions ensuing, or subsequent to, the enzyme-catalyzed aldol addition (Figure 10.27) [134—137]. 

By analogy with aromatic nitro compounds, nitroolefins such as yS-nitrostyrene 1032 react with the O-silylketene acetal 1033 at -78 °C, in the presence of the selective Lewis acid MAD, in toluene, to give a 6.3 1 syn/anti mixture of the co-nitro ester 1034 and 94a [98] (Scheme 7.33). 

The m-nitro ester (5), with trm.NC)2= +0-71, is hydrolysed 63-5 times as fast as the unsubstituted ester (powerful electron-withdrawal markedly assisting eOH attack on the carbonyl carbon atom, and stabilising the transition state leading to the negatively charged tetrahedral intermediate) while the m-Me ester (6), with (Tm.MC = —0 07, is hydrolysed 0-66 times as fast as the unsubstituted ester (very weakelectron-donationslightly inhibiting eOH attack, etc.). 

Thus, the reaction of alkyl halides and a-halo esters with sodium nitrite provides a very useful synthetic method for nitroalkanes and a-nitro esters. However, ethyl bromoacetate is exceptional in that it fails to give ethyl nitroacetate on treatment with sodium nitrite.93 This is due to the acidic hydrogen of the ethyl nitroacetate, which undergoes a further reaction with sodium nitrite to give the oxidized products (see Section 6.1, which discusses the Nef reaction). In a similar way, the reaction of benzyl bromide with sodium nitrite at 25 °C gives benzoic acid predominantly. To get phenylnitromethane, the reaction must be carried out at low temperature (-16 °C) (Eq. 2.48).93... 

The Michael addition of the copper-zinc reagent derived from ethyl 4-bromobutyrate to the piperonal-derived nitroalkene proceeds cleanly to give the nitro ester, which is an intermediate for the synthesis of lycoricidine alkaloids (Eq. 4.85).107... 

Ytterbium triflate is an extremely effective catalyst for the Michael addition of a-nitro esters to enones in water (Eq. 4.110).149... 

The carboxylation of nitroalkanes with magnesium methyl carbonate followed by esterification gives a-nitro esters in 40-58% yield.14 Magnesium methyl carbonate is prepared by the saturation of a magnesium methoxide suspension in DMF with C02. More elegantly, sodium salt of nitroalkanes can he carboxylated by means of 1 -ethoxycarbonylbenzotriazole to give a-nitro esters in 55-80% yield (Eq. 5.7).15 Nitroacetic acids and its esters can serve as useful... 

The acylation of the carbanions derived from nitroalkanes with acyl imidazoles or alkoxy-carbonylimidazoles takes place at the carbon atom to yield a-nitro ketones or a-nitro esters, respectively (Eq. 5.10).21 The lithium salts of nitroalkanes were isolated and used in THF or DMSO in the original procedure. Later, potassium salts generated in situ on treatment with r-BuOK in DMSO are reactive enough to give a-nitro ketones in good yield (Eq. 5.11).22... 

The monoanions of primary nitroalkanes, phenylnitromethane, and a-nitro esters are all preferentially C-alkylated by cinnamyl acetate and 2-butenyl acetate in 50-89% yield in the presence of Pd catalyst (Eq. 5.51).75 The a-nitro ester gives the C-alkylate in 89% yield, but 2-nitropropane gives the C-alkylate in only 29% yield. The main product is cinnamaldehyde, which is derived from 0-alkylation.75a... 

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