Carboxylic acids aldoximes

Acyl nitronates (63) derived from primary AN are characterized by two types of such transformations the rearrangement into a-acetoxy aldoximes (219) and elimination of the corresponding carboxylic acids to form nitrile oxides (Scheme 3.63). 

Yields are frequently moderate for Scholl reactions. Aldoximes are not usually compatible with these harsh reaction conditions and are very sensitive to factors such as temperature and reaction time. Consequently, oxidation to the corresponding carboxylic acid is a major side-reaction. However, both the ketoxime (51) and the aldoxime (53) are reported to give good yields of the corresponding m-dinitro compounds, (52) and (54) respectively, on treatment with absolute nitric acid in methylene chloride followed by hydrogen peroxide. 

Notably, nitrile-degrading enzymes (e.g. nitrilase that converts the CN group to carboxylic acid, and nitrile hydratase that produces an amide function) have been described, and they co-exist with aldoxime-degrading enzymes in bacteria (Reference 111 and references cited therein). Smdies in this area led to the proposal that the aldoxime-nitrile pathway, which is implemented in synthesis of drugs and fine chemicals, occurs as a natural enzymic pathway. It is of interest that the enzyme responsible for bacterial conversion of Af-hydroxy-L-phenylalanine to phenacetylaldoxime, an oxidative decarboxylation reaction, lacks heme or flavin groups which are found in plant or human enzymes that catalyze the same reaction. Its dependency on pyridoxal phosphate raised the possibility that similar systems may also be present in plants . 

At that time, however, these reactions were not brought to the level of preparative synthesis of nitriles. The main obstacle seemed to be further transformation of the nitriles to acids. In some cases, upon treating al-doximes with alkalies, it was not at all possible to fix nitriles since they immediately converted to acids. The anti(E)-isomers exhibit an enhanced reactivity in these cases. Thus, when boiled in 2 N NaOH, -aldoximes are slowly converted to a mixture of the corresponding carboxylic acids and sy/i(Z)-aldoximes to evolve ammonia (36JA1227). Under these conditions for 4 hr the - and Z-benzaldoximes undergo 13 and 48% conversion to form benzoic acid in 10 and 38% yield, respectively. Analogously, the -and Z-oximes of furfural, under the same conditions for 1.5 hr, are converted to furan-2-carboxylic acid in 33 and 62% conversion and 18 and 49% yield, respectively. 

Miscellaneous derivatives are hydrolyzed back to the starting carbonyl compounds. Hienylhydtazones of ketones are converted into the parent ketones tqion treatment with manganese dioxide.Tosylhydra-zones react with molybdenyl chloride or tungsten tetrafluoride to give both aldehydes and ketones. Sodium peroxide converts aldoximes into carboxylic acids. 

Good to excellent yields of jfc/M-difluoridcs are obtained from the reaction of ketoximes with NO BF4, (HF) /pyridine. The reactions are carried out under very mild conditions (rt, Nj atmosphere. 5 h) and the method is applicable to alkyl aryl (entry 7). diaryl (entry 8), and dialkyl ketoximes (entries 1 -6). In the ca.se of aldoximes. oxidation occurs and carboxylic acids are obtained. The concentration of the hydrogen fluoride in pyridine has an important effect on the yield of the reaction. The best results are obtained in the case of pyridinium poly(hydrogcn fluoride) with 60 wt % hydrogen fluoride. With lower concentrations, the major... 

The azolides are able to participate in a wide variety of nucleophilic olysis reactions which form aldehydes, ketones, carboxylic acids, esters, amides, thiol esters, hydrazides and anhydrides (Scheme 143). In addition, 1-trifluoroacetylimidazole (252) is a convenient reagent for the conversion of aldoximes into nitriles (Scheme 144) (81601579). 

Sodium peroxide, Na202, a pale-yellow solid (mp 460 °C), is used very rarely. Some examples are the conversion of aldoximes into carboxylic acids [790] and the oxidation of ketones to esters (lactones) [728, 797]. 

Selective oxidation of polymethylpyrimidines.1 2,4-Di- and 2,4,6-trimethyl-pyrimidines are selectively oxidized to 4-carboxylic acids by a slight excess of Se02 in pyridine. Yields are about 40-65%. This increased reactivity of a 4-methyl group of polymethylpyrimidines is also observed in reaction with ethyl nitrite in liquid ammonia to form 4-aldoximes and with ethyl benzoate in the presence of KOC2H5 to form phenacyl derivatives. 

Carboxylic acid amides from aldoximes CH NOH —>- CONHj... 

Carbonyl regeneration from oximes. This transformation is usually carried out in MeCN, but for aldoximes the basicity of the solution must be regulated to pH5-7 in order to avoid oxidation of the released aldehydes to carboxylic acids. 

For this reason, cyanuric chloride is used as a chlorinating and dehydrating agent in organic synthesis. It transforms (preferably secondary) alcohols into alkyl halides, carboxylic acids into acid halides, hydroxy carboxylic acids into lactones and aldoximes into nitriles ... 

Treatment of the aldoxime 1 with sodium hypochlorite and NEts in the presence of the terminal alkyne 2 gave rise, after deprotection, to the isoxazole derivative 3, converted to 4 by EDCI coupling with the suitable carboxylic acid. Employing different terminal alk)mes and carboxylic acids a novel series of isoxazolylpropionic acid derivatives, proved potent antagonists of the a Pi integrin, was synthesised <01BMC2593>. 

The addition of nitrile oxides to a,P-unsaturated carboxylic acid derivatives opens up a route to chiral, substituted isoxazoline derivatives. The nitrile oxides are generated in situ via deprotonation with a base (e.g. triethylamine) starting from the chlorinated aldoxime as the precursor (solvents CHCI3, CH2CI2, ether, benzene, toluene temperature -78°C up to 110°C). In most cases only one of two possible regioisomeric adducts is formed. 

Oximes can be converted to their corresponding nitro compounds with Oxone and refluxing acetonitrile (eq 58). They can also be cleaved to their parent carbonyl compounds by Oxone in conjunction with glacial acetic acid, or silica gel/alumina and microwave irradiation (eq 58). Ketoximes and aldoximes are both converted to carbonyl compounds in high yields using the microwave and alumina procedure. Several of the above transformations are highlighted in the oxidative decarboxylation of a-amino acids to form ketones and carboxylic acids. ... 

Potassium hydroxide/ethylene glycol Carboxylic acids from aldoximes CH NOH -j... 

Carboxylic acid amides from aldoximes s. 17, 211 GH NOH GONHg... 

The preparation of cyanides by dehydration is best accomplished from aldoximes (standard method) rather than from carboxamides, because the former require milder reaction conditions. However, carboxamides, as carboxylic acid derivatives, are more easily accessible. Phosgene has been applied in the dehydration of carboxamides rather than of aldoximes. 

Complex M(AAOPD), (18) (M = Co or Cu), catalyses the oxidation of aldoximes, ketoximes and carboxylic acids by dioxy iodobenzene (oxidant) in the presence of imidazole to corresponding carbonyl products in high yields. The rate of oxidation of oximes in the presence of Cu(AAOPD) is higher than that with Co(AAOPD) no such effect is observed in the oxidation of carboxylic acids. " ... 

---