Hydroxylamine hydrochloride oxime synthesis

Although harmine 52 is frequently obtained by isolation (or purchase order), a synthesis of this compound as well as a number of analogs has recently appeared [47,48]. The key step to this synthesis was the thermal electrocyclization of oxime intermediate 55, which was prepared by acylation of vinylindole derivative 54 followed by treatment with hydroxylamine hydrochloride. Neither oxime 55 nor its ketone precursor were isolated— instead, the crude reaction mixture was heated at reflux in o-dichlorobenzene to ultimately yield harmine in 56% yield overall starting from 54 (Fig. 18). 

Axenrod and co-workers reported a synthesis of TNAZ (18) starting from 3-amino-l,2-propanediol (28). Treatment of (28) with two equivalents of p-toluenesulfonyl chloride in the presence of pyridine yields the ditosylate (29), which on further protection as a TBS derivative, followed by treatment with lithium hydride in THF, induces ring closure to the azetidine (31) in excellent yield. Removal of the TBS protecting group from (31) with acetic acid at elevated temperature is followed by oxidation of the alcohol (32) to the ketone (33). Treatment of the ketone (33) with hydroxylamine hydrochloride in aqueous sodium acetate yields the oxime (34). The synthesis of TNAZ (18) is completed on treatment of the oxime (34) with pure nitric acid in methylene chloride, a reaction leading to oxidation-nitration of the oxime group to em-dinitro functionality and nitrolysis of the A-tosyl bond. This synthesis provides TNAZ in yields of 17-21 % over the seven steps. 

A small number of examples is available for the synthesis of E and Z isomers of oximes. In many cases, E isomers were obtained either from the Z forms (by the hydrochloride method) or isolated by column chromatography. Often, the reagents that have been used for oximation of aldehydes and ketones also catalyze the interconversion of Z and E isomers. The rate of equilibration of a mixture of Z and E isomers and the position of the equilibrium is temperature-dependent ". In 2001, Sharghi and Sarvani reported a convenient method for controlling the stereochemistry of the reaction of hydroxylamine hydrochloride with aldehydes or ketones in the solid state. The highly stereoselective conversion of aldehydes and ketones to their corresponding oximes... 

The two reactions in Step A were taken from the literature and were improved for the present synthesis. All previously related syntheses of arylacetophenone oximes found in the literature have used a threefold excess of hydroxylamine hydrochloride that is, however, not necessary in the present protocol. 

Synthesis (Freed and Potoski (American Home), 1971 Freed, 1973 Kleemann et al., 1999,) Dezocine is prepared through the following sequence The condensation of 1-methyl-7-methoxy-2-tetralone with 1,5-di-bromopentane by means of NaH or potassium tertbutylate affords 1 -(5-bromopentyl)-1 -methyl-7-methoxy-2-tetralone this product is cyclized with NaH to give 5-methyl-3-methoxy-5,6,7,8,9,10,11,12-octahydro-5,11 -methano-benzocyclodecen-13-one i. The ketone i, by reaction with hydroxylamine hydrochloride in pyridine, is converted into its oxime ii, which is reduced with H2 over Raney Ni to a mixture of isomeric amines which were separated by crystallization of the HCI salts giving 5-a-methyl-3-methoxy-5,6,7,8,9,11 a, 12-octahydro-5,11 -methanobenzo-cyclodecen-13p-amine, which is finally cleaved with concentrated HBr. 

SYNTHESIS To a well stirred solution of 14.8 g hydroxylamine hydrochloride in 120 mL MeOH there was added 3.6 g of 3,4-methylenedioxyphenylacetone (see under MDMA for its preparation) followed by 1.0 g sodium cyanoborohydride. The oxime, prepared from the ketone and hydroxylamine in MeOH with pyridine, may... 

The oximes of ketones with large hydrocarbon radicals like the acetyl-phenanthrenes are readily prepared by die action of hydroxylamine hydrochloride in the presence of pyridine. Special studies have been made for the synthesis of 1,2-cyclohexanedione dioxime as well as the next higher homolog. Dimethylglyoxime, CH,C(=NOH)C(=NOH)CH is... 

The readily available 2,3,4,6-fefra-O-benzyl-D-glucopyranose (11) can be used for the synthesis of both nojirimycin (1) and 1-deoxynojirimycin (2) (Schemed).It was treated with EtSH to furnish 12, which was oxidized to the corresponding ketone 13 using TPAP, while the Swern oxidation method failed to produce 13. Treatment of 13 with mercury(ll) salts in the presence of methanol followed by treatment with hydroxylamine hydrochloride in the presence of pyridine afforded the oxime 14 in 73% yield. Treatment of 14 with LiAlH4 in diethyl ether followed by N-protection of the resulting diastereomeric mixture of amines with di-rert-butyl dicarbonate furnished 15 and 16 in 65 and 15% yield, respectively. Pearlman s catalytic hydrogenation of 15 over palladium hydroxide in ethanol followed by treatment of the resulting tetrol with SO2 in water furnished the sulfonic acid 17 in 80% yield. Conversion of 17 into 1 was accomplished by treatment with Dowex 1X2 (OH ) resin. 

EM 9-oxime (11), a key compound of roxithromycin synthesis, is known to increase acid stability by reducing intermolecular ketalization but also diminishes the antimicrobial activity compared with EM (1) [3-5]. Compound 11 was obtained by the reaction of EM with hydroxylamine hydrochloride in a methanol solution in the presence of triethylamine (Scheme 2) [6]. The isolated EM oxime... 

Flavanones and Isoflavanones.- Reaction of the aryl benzyl ketone (120) with formaldehyde and dimethylamine has provided a new synthesis of isoflavanones in good yield.126 The same ketones can be cyclized to isoflavanones in good yield by treatment with di-iodomethane, a phase transfer catalyst (tetrabutylammonium iodide) and sodium thiosulphate.127 Flavanones react with hydroxylamine hydrochloride in ethanol-pyridine to give the oxime and not the oxazoline as previously claimed but when the oxime was heated with trifluoroacetic acid, the oxazoline was formed.128 The first triphenylmethane derivative to be found in nature, the flavanone melanervin (121), has been synthesized. Ammals (not animals, as printed in the abstract ) such as (122) have been applied to the... 

The synthesis of the carboacyclic analogs may be performed by constructing the heterocyclic ring on a suitable functionalized side chain. Thus, the acetal 489 was synthesized in a similar manner to 426. Its reaction with hydroxylamine hydrochloride gave a mixture of the oxime 490 and nitrile... 

Originally they were prepared by reaction of oxime with anhydrous hydrogen cyanide (82,131,132), Subsequently the oxime was added to an aqueous solution of hydroxylamine hydrochloride, sodium cyanide and sodium hydrogen phosphate (131), Lastly hydroxylamine hydrochloride, aldehyde and sodium cyanide may be mixed in a one-pot synthesis (79). 

This conversion is generally achieved by converting the aldehyde into oxime followed by its dehydration by a variety of reagents. One pot synthesis has also been developed , but these methods suffer from a number of drawbacks. In the microwave assisted reaction, the aldehyde is converted into oxime by reaction with hydroxylamine hydrochloride and potassium fluoride on alumina... 

A particular application of the synthesis of 4-ylidenebutenolides via acetylenic precursors is shown in Scheme 8 for the case of derivatives of the fungal metabolite patulin (10). Reaction between the acetylenic Grignard reagent (114) and keto-acetal (115) led first to (116) which by Wittig condensation with methoxycarbonylmethylenetriphenylphospho-rane was converted into a mixture of Z- and iE -isomers of ester (117). Saponification of the mixture of isomers then led to an isomeric mixture of the corresponding carboxylic acids, one of which, the Z-isomer (118) was cyclized to the butenolide (119). Acidic hydrolysis of (119) in the presence of hydroxylamine hydrochloride then gave the oxime derivative (120) of natural patulin 110). 

Benzofurans and Other Annelated Furans.-A new synthesis of benzofurans (73) is by the reaction of the phosphonium salt (72) with acid chlorides RCOCl in the presence of triethylamine. The benzofuran (74) results from the condensation of hexafluorobenzene with acetylacetone. Three instances of the formation of benzofurans from O-aryl-hydroxylamines, i.e. the oxygen analogue of the Fischer indole synthesis, have been reported O-phenylhydroxylamine hydrochloride and benzenesulphonylacetone give a 2 1 mixture of compounds (73 R = CH2S02Ph) and (75), the oxime ether (76) is converted into the aldehyde (77 ... 

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