Nitrones hydrolysis

Scheme 5 Synthesis of an TV-Hydroxyamino Ester by Nitrone Hydrolysis 271...

The [4+2] cycloaddition of 3-nitrocoumarins with electron rich dienophiles proceeds with high . 

Krohnke aldehyde synthesis. Transformation of benzyl halides into aldehydes via their pyri-dinium salts which, on treatment with p-nitrosodi-methylaniline, give nitrones. Hydrolysis of the nitrones yields aldehydes. 

Other approaches to (36) make use of (37, R = CH ) and reaction with a tributylstannyl allene (60) or 3-siloxypentadiene (61). A chemicoen2ymatic synthesis for both thienamycia (2) and 1 -methyl analogues starts from the chiral monoester (38), derived by enzymatic hydrolysis of the dimethyl ester, and proceeding by way of the P-lactam (39, R = H or CH ) (62,63). (3)-Methyl-3-hydroxy-2-methylpropanoate [80657-57-4] (40), C H qO, has also been used as starting material for (36) (64), whereas 1,3-dipolar cycloaddition of a chiral nitrone with a crotonate ester affords the oxa2ohdine (41) which again can be converted to a suitable P-lactam precursor (65). 

Like isomerization of oxaziridines to nitrones, acid hydrolysis of oxaziridines proceeds with conservation of the N—O bond. Both reactions are related mechanistically and are... 

The reason for the slow hydrolysis compared to that of structurally similar compounds like nitrones or 0,lV-acetals might be the following (b-67MI50800) in the protonated species (77) assistance of the lone pair of electrons at nitrogen is sterically hindered due to the large angle of its orbital to the plane of the ring. 

Bonnett et alJ observed the formation of the pyrrolidone hydrox-amic acid (66) as a by-product in the alkaline hydrolysis of a 2-cyano-nitrone (69). This displacement of cyanide by hydroxyl seems to be quite general. 

The UV and IR spectra eliminate structures with a CN double bond. The isomerism of nitrones and oxaziranes thus cannot be a result of CIS or traris arrangement of substituents about a double bond. The carbon atoms of an oxazirane are still at the oxidation level of the carbonyl compound used in its syntheses. By acid hydrolysis, for example, 2-terf-butyl-3-phenyloxazirane (9) can be split into benzaldehyde and tert-butylhydroxylamine fEq. (8)]. ... 

Nitrocyclo ilkanones can be successfully C- dlylated by PdfO -catiilyzed reacdon v/ith various dlyl carbonates and 1,3-dienemonoepoxldes under neutriil condidons, as shown inEqs 5 56 and 5 57, respecdvely The product of Eq 5 56 is converted into cyclic nitrone via the reducdon of nltro group v/ith H -Pd/C followed by hydrolysis and cyclizadon... 

Treatment of 2- 5//-dibenz[i>,/]azepin-5-yl acetaldehyde (16), prepared in 68% yield by /V-alkylation of 5/7-dibenz[A,/]azepine with bromoacetaldehyde diethyl acetal followed by acid hydrolysis, with methyl hydroxylamine yields the isolable nitrone 17, which in refluxing toluene undergoes intramolecular 1,3-dipolar cycloaddition at the CIO —Cl 1 alkene bond to give 2,3,3a, 12b-tetrahydro-2-methyl-3,8-methano-8//-dibenz[i>,/]isoxazolo[4,5-r/]azepine (18).235... 

At present there is no more than indirect evidence for the existence of the halogeno-halothiophosphoric acids and the dibromo compound. So the unsoluble nitron dibromo-phosphate precipitates in case of the partial hydrolysis of POBr3 in acetone and in presence of nitron (5). Further the partial hydrolysis of PSCI3 and PSCI2F in presence of big cations, such as tetraphenylphosphonium or -arsonium yields stable salts (22), which suggests the primary formation of the free acid in the solution ... 

In comparison to the chloro compounds the dibromophosphates are by far less thoroughly investigated. Grume et al. were the first to succeed in the isolation of the nitron salt of dibromophosphoric acid, by partial hydrolysis of POBr3 in cooled aceton solution 8). Later on it could be shown, that even CaO and MgO form solvatated... 

The nitro group can be converted to a ketone by hydrolysis of the nitronate anion, permitting the synthesis of 1,4-dicarbonyl compounds. 

The 1,4-addition of RMgX or RLi to nitroalkenes produces nitronate intermediates, which are converted into nitroalkanes, nitrile oxides (oxime chlorides), or carboxylic acids, depending on the conditions of hydrolysis (Scheme 4.14).94... 

The use of oxygen-containing dienophiles such as enol ethers, silyl enol ethers, or ketene acetals has received considerable attention. Yoshikoshi and coworkers have developed the simple addition of silyl enol ethers to nitroalkenes. Many Lewis acids are effective in promoting the reaction, and the products are converted into 1,4-dicarbonyl compounds after hydrolysis of the adducts (see Section 4.1.3 Michael addition).156 The trimethylsilyl enol ether of cyclohexanone reacts with nitrostyrenes in the presence of titanium dichloride diisopropoxide [Ti(Oi-Pr)2Cl2], as shown in Eq. 8.99.157 Endo approach (with respect to the carbocyclic ring) is favored in the presence of Ti(Oi-Pr)2Cl2. Titanium tetrachloride affords the nitronates nonselectively. 

A convenient route to j3-phosphorus nitroxides involves the 1,3-addition of trimethylsilyl phosphites (e.g., diethyl) or trimethylsilyl phosphines (e.g., diphenyl) to aldo nitrones (e.g., a-PBN, DMPO), or keto nitrones (e.g., 2-Et-DMPO or 2-Ph-DMPO), to form a-phosphityl- or a-phosphinyl-O-silylhydroxyl-amines. Acidic hydrolysis provides the corresponding hydroxylamines which are easily oxidized to p-phosphorus-nitroxides (690). 

Regardless of the coordination mode of the boron atom, boryl nitronates are rather smoothly subjected to alkaline hydrolysis to give, after acidification, the corresponding nitroalkanes (217, 230, 316). Depending on stability of the aci form, the yields of nitroalkanes obtained vary from moderate to high (Scheme... 

If such SENA contains the proton at the a-C atom (203), trimethylsilanol is eliminated, which causes partial hydrolysis of the nitronate. 

Feuer and co-workers extended their studies to the alkaline nitration of a,Nitration with potassium ferf-butoxide and amyl nitrate in THF at —30 °C yields the corresponding dipotassium salt of the a,nitronate salts from these reactions are isolated via methanol-induced precipitation from the aqueous reaction liquors, a process which also separates the product from impurities. These salts undergo hydrolysis on treatment with aqueous potassium hydroxide, and subsequent acidification yields the corresponding Q, y-dinitroalkane. This route has been used to synthesize 1,4-dinitrobutane (27) from apidonitrile (95) in 30 % overall yield. 

Treatment of nitrones 85 with lithium and DTBB (10%) in THF at room temperature yielded, after hydrolysis, the corresponding imines 86 (Scheme 36) . 

II. HYDROXYLAMINES THROUGH HYDROLYSIS OF HYDROXAMIC ACIDS, OXIMES AND NITRONES... 

Hydrolysis of nitrones, oximes and hydroxamic acids is frequently used as a final step in the preparation of substituted hydroxylamines. Although hydrolysis is the most commonly utilized method for oximes, oxime ethers and nitrones, formation of sensitive hydroxylamines can also be achieved under milder reaction conditions by treatment of... 

To avoid overoxidation, primary amines (e.g. 128, equation 89) can be converted into Schiff bases with an aromatic aldehyde. Subsequent oxidation of the resultant imines 129 with an excess of peracids produces oxaziridines 130 and/or nitrones 131. Both of them produce hydroxylamines 132 (equation 89) upon hydrolysis in moderate to good overall yields. Yields of hydroxylamines are considerably better if anisaldehyde instead of benzaldehyde is used for the protection . ... 

Alternatively, some of the desired amino acid functionality may be contained within the nitrone fragment, as in the synthesis of homochiral allyl glycines by Katagiri et al. (151), which reveals the carboxylate by hydrolysis of a lactone in the dipole (Scheme 1.24). Here, thermolysis of nitroso Meldrum s acid (112) via a nitrosoketene intermediate 113 and reaction with 1-menthone gave the separable nitrones 114a (26%) and 114b (28%) by a [3 + 2] cycloaddition, although a... 

Katagiri et al. (48,322,323) applied L-menthone and an in situ generated nitroso ketene for the synthesis of nitrone 212, as shown in Scheme 12.61. The nitrone showed high selectivities in reactions with various allyl silanes. High pressure or the presence of BF3 Et20 was required for the reaction to proceed. In the reaction of 212 with allyltrimethylsilane in the presence of BF3 -Et20, isoxazolidine (213) was obtained as the sole product. After hydrolysis and hydrogenolysis. 

Acid hydrolysis of the nitrone provides the aldehyde corresponding to the original alkyl halide (the Krohnke oxidation) (Scheme 67) (53AG605). 

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