Methoxyamines

Ketones may also be converted into amines, if they are first reacted with ammonium salts ot methoxyamine and then reduced with sodium trihydrocyanoborate at pH 7, where carbonyl groups are not attacked (M.-H. Boutigue, 1973). 

An interesting set of central nervous system properties has also been discovered and studied (Table VI-10). The work devoted to piscaine must be emphasized besides finding hypnotic properties of 2-amino-4-phenyl-thiazole on fish, the authors studied the structure of the metabolite, as well as the localization of the (radio labeled) metabolic product in various organs. Recently, thiazol-4-yl methoxyamine was shown to inhibit the development of morphine tolerance (1607). 5-Aminothiazole derivatives such as 419a were proposed as cardiovascular agents (1608, 1610). Substitution of the 5-aminothiazole radical on the cephalophosphorin structure gives a series of antibacterial products (1609). 

Direct aminadon of 3-nitropyridines v/ith methoxyamine in the presence of zinc chloride under basic conthdons proceeds to give 3-amino amino-3-nitropyridines fEq 9 51 ... 

Amination of living polystyrene or polyisoprene was attempted by means of a binary reagent (methoxyamine/methyllithium). However the yields were not quite quantitative 61... 

In the presence of zinc chloride, stereoselective aldol reactions can be carried out. The aldol reaction with the lithium enolate of /-butyl malonate and various a-alkoxy aldehydes gave anti-l,2-diols in high yields, and 2-trityloxypropanal yielded the syn-l,2-diol under the same conditions.633 Stoichiometric amounts of zinc chloride contribute to the formation of aminoni-tropyridines by direct amination of nitropyridines with methoxyamine under basic conditions.634 Zinc chloride can also be used as a radical initiator.635... 

A new synthesis of [i-nitroenamines by amination of nitroalkenes with methoxyamine in the presence of base is reported (Eq. 4.23).29... 

The amination of a,a)-dilithiumpolystyrenes was effected using two equivalents of the reagent generated from methyllithium and methoxyamine in a benzene/THF (80/20, v/v) mixture with the results shown in eq. 4. 

Cheney et al. (1995) analyzed steroids by coupling an HPLC purification step with GC/MS. The steroids were initially characterized by their HPLC retention times compared with the retention times of tritium-labeled recovery standards. Next, the nemosteroids were characterized by their GC retention times. Finally, they were identified by their unique fragmentation spectra following derivatization with heptafluorobutyric anhydride or methoxyamine hydrochloride. For structmal identification, the mass spectra were compared to appropriate reference standards. This approach is highly specific, and its sensitivity is increased by the use of SIM. The detection limit for measuring allopregnanolone achieved in the 1995 study was 0.63 pmol (0.2 ng) starting from 100-300 mg of brain tissue. 

An acyclic methoxyamine, 0-methylephedrine 333, plays a similar role in the diastereoselective Uthiation of 334. Substitution with 335 gives 336 from 322, and lithiation of 334 typically gives products 335 with >90 10 diastereoselectivity (Scheme 149) . Auxiliary removal is possible by quaternization and substitution with dimethylamine (giving 336) or other nucleophiles, producing potential ligands with planar chirality only. Usefully, the products formed by this method are enantiomeric with those formed by most other auxiliary methods when the more readily available enantiomers of the starting materials are used. 

Another approach to secondary amines has been reported (J. Am. Chem. Soc. 125 16178, 2003) by Masakafsu Shibasaki of the University of Tokyo. Addition of methoxyamine to a chalcone 7 (alkyl enones work in slightly lower ) gives the amine 8. The amine 8 can be reduced with high stereocontrol to the amino alcohol 9. K-Selectride gives the complementary diastereomer. 

Methoxyamine hydrochloride [593-56-6] M 83.5, m 151-152°. Crystd from absolute EtOH or EtOH by addition of ethyl ether. [Kovach et al. JACS 107 7360 1985],... 

Acetophenone 0-methyloxime is reduced by incremental addition of the substrate and borane to the homogeneous catalyst system to result in the formation of the corresponding methoxyamine in 67 % ee and in 860% chemical yield based on the chiral auxiliary (Scheme 14) (37). 

Allyltributyltin, 10 Boron trifluoride etherate, 43 Di-jjL-carbonylhexacarbonyldicobalt, 99 Grignard reagents, 138 Ketenylidenetriphenvlphosphorane, 154 Methoxyamine, 177 Reformatsky reagent, 346 Tin(IV) chloride, 300 Tributylcrotyltin, 10 Aldol reactions General considerations, 202 Directed aldols using imines Norephedrine, 200... 

Lithium aluminum hydride-Hexa-methylphosphoric triamide, 159 Methoxyamine, 177 Titanium(III) chloride-Diisobutyl-aluminum hydride, 303 Trimethylsilyl chlorochromate, 327 From vinylsilanes m-Chloroperbenzoic acid, 76 Miscellaneous methods to prepare ketones... 

Another potentially useful amination procedure utilizes the reaction of organo-lithium compounds with mixtures of methoxyamine and methyllithium (Eqn. (85)) 343> for example ... 

Formation of aldimines from propanal and octanal. To a stirred solution (0°C) of 10 mmol of the methoxyamine dissolved in 30 ml of benzene (CAUTION) (previously washed with concentrated sulphuric acid and distilled) is added 10 mmol of the pure aldehyde. An immediate cloudiness usually results. The mixture is allowed to warm to room temperature and c. 15 g of anhydrous sodium sulphate added. After stirring an additional 30-40 minutes, it is filtered and the sodium sulphate washed thoroughly with dry ether. The solvent is removed first with aspirator pressure and then with a vacuum pump (0.5 mm) to generally furnish 9.5-10 mmol of the aldimine as a colourless oil. The aldimines are dissolved in tetrahydrofuran (0.4 m) and stored at —20 to — 30 °C. Attempts to store the aldimines as neat liquids result in deterioration. The solutions of aldimines are conveniently transferred via a syringe to reaction vessels. 

The chiral methoxyamine is recovered from the aqueous solution by neutralisation with solid potassium hydroxide and extraction with ether. The ethereal extract is washed with brine, dried over potassium carbonate and concentrated to give the crude chiral amine in 80-88 per cent yield. Distillation affords the pure amine (70-75% recovery) with [a] values which indicate that no racemisation has occurred. 

Rli-rRNH2. Various organolithium reagents are converted into the corresponding primary amines by treatment with 2 equiv. each of methoxyamine and methyllithium in hexane-ether. Yields are in the range 55 95%. Omission of methyllithium or substitution by n-butyllithium markedly reduces the yield. In fact, use of methoxyamine alone for amination of organometallics was first reported in... 

Mercury(II) pivalate, 319 Mercury(II) trifluoroacetate, 320 Mesembranol, 169 a-Methallyl alcohol, 258 Methanesulfinyl chloride, 248 Methanesulfonic acid, 321 Methanesulfonyl chloride, 322 Methanol-sodium tetraborate, 322 Methoxyamine, 322-323 et Methoxy-a-arylacctic acid esters, 411 p-Methoxybenzyl ethers, 166, 167 Mcthoxycarbonylketene, 340, 341 4(R)-Methoxycarbonyl-l,3-thiazolidine-2-thione, 323-324... 

N-ALKYLAMINES Mercury(II) nitrate. Methoxyamine. Sodium methoxide. 

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