Oxime ethers formation

A method for protecting ketones and aldehydes is the formation of oximes, but sometimes further protection of the oximes is required. For this purpose, the oximes can be protected as allyl ethers. The oxime ethers ean be eleaved with triethylammonium formate in boiling dioxane[444]. The allyl ether of oximes is eleaved under mild conditions without attaeking the aeetal group in 677. 

MILLER - SNYDER Aiyl Cyanide Synthesis Synthesis of benzonitnies from aldehydes via oxime ethers Formation of p-cyanophenol from p nrtrobenzaldoxime and p-nitiobenzonitnle (used as a sometimes recyclable chain carrier)... 

Schiff bases are obtained from 2-aminoimidazothiadiazoles with aldehydes (77M665). Hydrazones and oxime ether formation of imidazothia-diazole-5-carbaldehydes and -5-ketoesters was reported (84FES585 95EUP662477). Reduction of 122 with Al/FIg yields the tautomeric imine 128 of the corresponding amine (83JHC1003). 

FIGURE 8.3. Improved oxime ether formation in the presence of copper sulfate... 

Tollen s test, described previously, can be used to distinguish between the aldehyde and -the ether. Also, oxime formation with hydroxylamine, and Schiff test with the fuchsin-aldehyde reagent to fom a characteristic magenta color can be used. 

Mesityl oxide Methyl benzoate Nitroethane Propyl alcohol Propylene dichloride Tetrahydrofurfuryl alcohol Trichloroethylene solvent, cellulose ethers Acetone oxime Acetophenone Butyl benzoate Butyl formate Cyclohexane Cyclohexyl acetate Dibutyl tartrate Diethyl oxalate Epichlorohydrin Ethyl butyrate Ethylene glycol diacetate Ethyl-(S)-lactate Ethyl propionate Isopropyl butyrate Mesityl oxide... 

As discussed earlier (see also Chapter 6), oxime derivatives are often prepared for polyfunctional compounds containing ketone groups in order to prevent the formation of mixed enol-silyl ethers. An alternative approach is to use a catalyst to enhance the yield of enol-silyl ethers (see also above. Section 4.2.3, for TMS ethers). The use of potassium acetate in toluene as catalyst is reported to produce a quantitative yield of TBDMS ethers and >96% yield of TBDMS-enol ethers of a, -unsaturated keto steroids [326]. An alternative to this approach, set out below, uses sodium formate to catalyse enol-silyl ether formation with fewer by-products being produced [12, 13]. 

More importantly, some silylating reagents used for protection of functional groups with active hydrogen atoms can react with carbonyl fragments with the formation of trimethylsilyl (TMS) derivatives of enols. If such unpredictable mode of derivatization is undesirable, all carbonyl fragments should be protected before silylation, for example, by conversion into alkoxyimino groups (alkyl ethers of oximes, see below). 

Dimethyl ketals and enol ethers are stable to the conditions of oxime formation (hydroxylamine acetate or hydroxylamine hydrochloride-pyridine). Thioketals and hemithioketals are cleaved to the parent ketones by cadmium carbonate and mercuric chloride. Desulfurization of thioketals with Raney nickel leads to the corresponding methylene compounds, while thioenol ethers give the corresponding olefin. In contrast, desulfurization of hemithioketals regenerates the parent ketone. ... 

A mixture of 3 -hydroxypregna-5,l6-dien-20-one acetate (10 g), 70 ml of ethanol and 2 ml of methoxylamine is refluxed for 12 hr (Note methoxyl-amine hydrochloride leads to oxime formation). After cooling, another 1.75 ml of methoxylamine is added and the reaction is refluxed for another 12 hr. The solvent is removed in vacuo and the residue is dissolved in ether. Hydrogen chloride gas is passed into the ether solution and the white crystalline salt (113) is filtered off and washed with ether (85% yield crude mp 228-229°). 

If the carbonyl grou]) in the 3-position of N-methylisatin or tlii-ana])hthencquinone is blocked by formation of an oxime (cf. 112), A -methylation of the oxime group occurs instead of ring expansion on reaction with diazomethane. In methanol, thianaphthenequinone oxime iV-mcthyl ether (113) then undergoes ring opening catalyzed by diazoniethane (113 114). 

The pharmacological versatility of this general substitution strategy is further illustrated by diazonium coupling of 14 with 2-nitrobenzenediazonium chloride to produce biarylal-dehyde 18. Formation of the oxime with hydroxylamine is followed by dehydration to the nitrile. Reaction with anhydrous methanolic hydrogen chloride leads to imino ether and addition-elimination of ammonia leads to the antidepressant amid-ine, nitrafudam (20). ... 

Compound 14 can be dismantled in a productive fashion by ret-rosynthetic cleavage of the indicated bonds (see Scheme 4). The intermolecular attack of the amino group in 15 upon the keto function in 16 would be expected to result in the formation of the desired oxime ether after loss of a water molecule. A few functional group manipulations would then complete the synthesis of intermediate 14. A valuable structural feature of 15 is the C-2 oxygen substituent. Although this oxygen atom is not expressed in the natural product, it would certainly play an important role in our... 

The oxime (an isomer of ethylnitrolic acid ) decomposes gradually at ambient temperature, but explosively above 110°C [1], The product from treatment of nitromethane with strong sodium hydroxide solution at 50°C, followed by acidification and ether extraction, gave, after vacuum evaporation, a residue which exploded when air was admitted. On this occasion, a weekend elapsed between alkali and acid treatments, and it seems possible that formation of fulminic acid derivatives may have occurred [2], A 75 g sample of methazonic acid, from a preparation which had transiently overheated to 70°C, during the addition of nitromethane to sodium hydroxide solution, was stored for a week at — 15°C, then allowed to warm to room temperature. Twelve hours later it spontaneously detonated, destroying a fume hood. There is no evident cause for this explosion [3], It seems sensible to... 

Quinone dyes, 9 503 Quinone ketals, anodic oxidation of hydroquinone ethers to, 21 264 Quinone methides, 2 209-211 Quinone Michael addition chemistry, 21 248-249, 250, 252 Quinone monoacetals, 21 251 Quinone monoimine (QMI), 19 246 Quinone oximes, formation of,... 

In qualitative terms, the rearrangement reaction is considerably more efficient for the oxime acetate 107b than for the oxime ether 107a. As a result, the photochemical reactivity of the oxime acetates 109 and 110 was probed. Irradiation of 109 for 3 hr, under the same conditions used for 107, affords the cyclopropane 111 (25%) as a 1 2 mixture of Z.E isomers. Likewise, DCA-sensitized irradiation of 110 for 1 hr yields the cyclopropane derivative 112 (16%) and the dihydroisoxazole 113 (18%). It is unclear at this point how 113 arises in the SET-sensitized reaction of 110. However, this cyclization process is similar to that observed in our studies of the DCA-sensitized reaction of the 7,8-unsaturated oximes 114, which affords the 5,6-dihydro-4//-l,2-oxazines 115 [68]. A possible mechanism to justify the formation of 113 could involve intramolecular electrophilic addition to the alkene unit in 116 of the oxygen from the oxime localized radical-cation, followed by transfer of an acyl cation to any of the radical-anions present in the reaction medium. 

Wordy Over the past few years, we have encountered numerous examples of water as the perfect solvent. We observed this first in osmium-catalyzed dihydroxylation reactions and also in nucleophilic ring-opening reactions of epoxides. We also observed this in cycloaddition reactions and in most oxime ether, hydrazone, and aromatic heterocycle condensation processes.Finally, we observed it in formation reactions of an amide from a primary amine and an acid chloride using aqueous Schotten-Baumann conditions. ... 

Transformations on the keto group of benzo[c]thieno[3,2-/][l,2]thiazepin-4(9H)-one 313 and isomeric benzo[c]thieno[3,4-/][l,2]thiazepin-10(5H)-one (not depicted in the Scheme) include reduction with sodium borohydride to afford alcohol 314 and formation of oximes (Scheme 67, Section 3.3.1.2 (1997JHC1191, 1998PHA130)). The later can be further O-alkylated to 2-aminoethyl 315 (2003FES1, 1996AP352). Similarly, substituted 2-aminoethyl ethers 316 were synthesized using two alternative routes (2000JHC389). 

Oxime ethers have a >C=N—O—C—substrucmre. Table 5 presents the enthalpy of formation data for such species where there is little structural commonality save the functional group of interest. 

TABLE 5. Enthalpies of formation for oxime ethers and esters (kJmol... 

The 3-nitroisoxazoline has gas and liquid phase values available. Given the absence of knowledge about isoxazolines, we accept these data and use them in what follows. We are told that the dehydration reaction of 3-phenyl-A -isoxazoline-5-ol (an oxime ether) to form 3-phenylisoxazole (equation 42) is exothermic by 16 kJmol. The gas phase enthalpy of formation of the latter species is 139.5 6.2 kJmoG. (As the isoxazoles are nominally aromatic, they are not included here as unsaturated oxime ethers.)... 

Interestingly, two of the other species in Table 3 are nitrolates, i.e. ethers of a-nitrooximes, an otherwise thermochemically unprecedented class of compounds. We already have briefly discussed one, 3-nitroisoxazoline, and the second is 1-nitroacetaldehyde 0-(l,l-dinitroethyl)oxime (ONo-ld-dinitroethyl acetonitronate), MeC (NOala—O—N=C(N02)Me. The latter acyclic species is a derivative of 1,1-dinitroethanol—we know of the enthalpy of formation of no other a-nitroalcohol or derivative. Nonetheless, we may ask if the two calorimetric data are internally consistent. Consider the condensed phase reaction 47, which involves formal cleavage of the O — bond in the nitroisoxazoline by the C—H bond of the dinitromethane. It is assumed that the isoxazoline has the same strain energy as the archetypal 5-atom ring species cyclopentane and cyclopentene, ca 30 kJ mol . ... 

---