Amines, preparation from oximes

The most general method for synthesizing amines involves the reduction of oximes and imine derivatives obtained from aldehydes or ketones (see Sections 5.5.2 and 4.3.11). By catalytic hydrogenation or by LiAltLj reduction, while 1° amines are prepared from oxime or unsubstituted imine, 2° amines are obtained from substituted imine. Unsubstituted imines are relatively unstable, and are reduced in situ. 

Amines, preparation from amides, 16, 4 from isothiocyanates, 18, 5 from ketones, 17, 76 from oximes, 11. S8 f -Aminobenzaldehyde, 13, 28... 

Many 1,2,3,5-benzenetetrol derivatives are used mediciaaHy. For example, khellin [82-02-0] (65), which is a naturally occurring benzopyranone, is used as a coronary vasodilator and bronchodilator (233). Derivatives of khellin are effective local anesthetics and antiarrythmics (234). Similarly, amine derivatives (68) that are prepared from khellinone oxime (66) exhibit hypnotic, sedative, anticonvulsant, antiinflammatory, cardiac analeptic, diuretic, and antiulcerous activity (235) (see Analgesics, antipyretics, and antiinflammatory agents). 

As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as usefid starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, ind pyrrolidines, are frequently prepared from nitro compounds. Syntheses of heterocyclic compounds using nitro compounds are described partially in Chapters 4, 6 and 9. This chapter focuses on synthesis of hetero-aromadcs fmainly pyrroles ind indolesi ind saturated nitrogen heterocycles such as pyrrolidines ind their derivadves. 

Asymmetric catalytic reduction reactions represent one of the most efficient and convenient methods to prepare a wide range of enantiomerically pure compounds (i.e. a-amino acids can be prepared from a-enamides, alcohols from ketones and amines from oximes or imines). The chirality transfer can be accomplished by different types of chiral catalysts metallic catalysts are very efficient for the hydrogenation of olefins, some ketones and oximes, while nonmetallic catalysts provide a complementary method for ketone and oxime hydrogenation. 

Archibald and co-workers used a similar strategy of amine oxidation, followed by oxidative nitration, for the conversion of 5,10-diaminodispiro[3.1.3.1]decane to 5,5,10,10-tetranitrodispiro[3.1.3.1]decane (21). 5,10-Diaminodispiro[3.1.3.1]decane was prepared from the redaction of the corresponding oxime (19) with sodium in liquid ammonia-methanol. 5,10-Dinitrodispiro[3.1.3.1]decane (20) nndergoes oxidative nitration to give 5,5,10,10-tetranitrodispiro[3.1.3.1]decane (21) in 64 % yield. 

PREPARATION OF a -ALKYLATED AMINES FROM OXIME SULFONATES WITH TRIALKYLALUMINUM - DIISOBUTYLALUMINUM HYDRIDE... 

Chiral 1,2-oxazines (33) have been prepared from achiral ketones, R -CO-CfT-R2, via an a-oximation step (with a tetrazolylpyrrolidine organocatalyst), followed by a Wittig reaction.87 Subsequent N—O cleavage yields enantiopure ds-allylic alcohols bearing a pendant amine. 

The C=N bond of simple imines possesses modest reactivity toward intermolecular radical additions, so such acceptors have rarely been exploited. To enhance their reactivity toward nucleophilic radicals, electron-withdrawing groups at the imine carbon have been effective, as demonstrated by Bertrand in radical additions to a-iminoesters prepared from chiral amines [25]. Also, more reactive oxime ethers have been exploited extensively for radical addition, mainly through the longstanding efforts of Naito [26]. In most cases, stereocontrol has been imparted through the substituents on the imino carbon chiral O-substituents on oximes for stereocontrol were ineffective, presumably due to poor rotamer control [27, 28]. 

A series of variously substituted chloro-androstanes (17 examples), bromo-androstanes (14 examples), and amino-androstanes (29 examples) prepared from the corresponding alcohols and oximes has been described.65 It was noted during the course of this work that all ring A, B, or C oximes were reduced by lithium aluminium hydride to yield over 90% of the corresponding axial amine, except at C-3 where 65% of the equatorial amine was isolated. This is in line with the lithium aluminium hydride reduction of 5a-cholestan-3-one where the equatorial hydroxy-steroid predominates. The observation was also made that when 3/8-, 7/3-, and 16/3-tosy oxy-5a-androstanes are heated with tetra-n-butylammonium hydroxide in... 

Oxime — imine. The low valent titanium reagent prepared from TiClj and diisobutylaluminum hydride (1 3) in THF reduces the oxime 1 to the very labile imine 2. Reduction of 2 to the corresponding amine with diisobutylaluminum... 

The nitroso chlorides prepared from limonene, sylvestrene, 3-carene, and a-pincnc have been converted to a-amino oximes by treatment with aliphatic and aromatic amines with unspecified yields39,42,43-15°-151. The configuration of the products was determined by NMR spectroscopy, molecular mechanics calculations and X-ray crystallographic analysis 50, in some cases reversing the configuration previously assigned. The stereochemical outcome of the reaction is rationalized by attack of the amine from the least hindered side of the intermediate nitroso alkene. 

Dimethylaniline has been prepared by reduction of the corresponding nitro compound, either chemically or catalyti-cally. It has been prepared from 3,4-dimethylphenol by heating with ammonia, ammonium bromide, and zinc bromide from w-toluidine hydrochloride by alkylation with methanol at high temperatures from anhydro-4-amino-2-methylbenzyl alcohol by dry distillation from calcium hydroxide from 2-methyl-S-aminobenzyl alcohol by reduction with sodium from 2-methyl-5-nitrobenzyl chloride and 2-methyl-S-nitrobenzyl acetate by catalytic reduction from o-xylene by direct amination with hy-droxylamine hydrochloride in the presence of aluminum chloride and from 3,4-dimethylacetophenone by the Beckmann rearrangement of the oxime.i" The present method has been published. ... 

Thus the 3-substituted isoquinolinium iodide 64, prepared from deoxypi-peroin 20 via the oxime 62 and the amine 63 as outlined in Scheme 11, was treated with an excess of ethereal diazomethane. When the resulting crude aziridinium iodide 65 in 6 iVhydrochloric acid was kept at room temperature for 1 week, ( )-reframidine (27) was isolated in 20% yield. Reframi ne was also formed, in 35% yield, when the 3-benzazepine 67, obtained in 20% yield by refluxing the crude aziridinium iodide 65 with 1% methanolic hydrogen chloride, was treated with 6 iVhydrochloric acid at ambient temperature for 1 week. 

There are a number of important methods worthy of merit for the synthesis of phosphorylglycines. Thus, electrophilic amination of diethyl l-(ethoxycarbonyl)methylphosphonate proceeds in one simple operation via the sodium salt in THF or DME. A variety of aminating agents are used with variable yields, such as 0-mesitylenesulfonylhydroxylamine (39 7%), chloramine (23-84%), and diphenyl (O-hydroxylamine)phosphine oxide (60%). Diethyl 1-ethoxycarbonyl- or l-(tert-butoxycarbonyl)methylphosphonate may also be efficiently transformed into oxime or diazo derivatives and then converted to an amine by a further reduction step. The oximes are prepared from EtONO via the sodium diethyl l-(tert-butoxycarbonyl)methylphosphonate (17% or 36%), from NOCl and diethyl l-(ethoxycarbonyl)methylphosphonate in the presence of tEtOljMg, Al-Hg, or Al(O7-Pr)3, 8 from NOCl and diethyl l-(methoxycarbonyl)ethylphosphonate, ° or from NOCl/ROH and diethyl l-tchlorocarbonyl)mclhy I phosphonate. ... 

A Acetophenone derivatives can be prepared from benzene by a Friedel-Crafts acylation. The derived oxime, formed using hydrox-ylamine, undergoes a Beckmann rearrangement to produce the amide hydrolysis yields the amine (Scheme 8.4). 

Beckmann rearrangement of the oxime (59), prepared from (56), gives the two amines (60). Ruschig degradation" (treatment of the iV-chloro-derivative with NaOMe) gives the nitriles (61). 

More complex monosaccharides such as daunosamine and fucose are assembled using a similar strategy (Scheme 31).- - Cyclocondensation of diene (104) with acetaldehyde (9f) using the lanthanide catalyst Eu(hfc)3 gives the syn cycloadduct (105). Treatment of (105) with TFA followed by oxymercuration [Hg(OAc)2-NaCNBH4] and reductive amination of the oxime acetate (derived from the ketone) gives daunosamine (108). Fucose (107) is prepared from compound (106) by reduction of the ketone and treatment of the glycal with MCPBA in methanol. 

Mannojirimycin (1) and 1-deoxymannojirimycin (2) were prepared from 2,3 5,6-di-0-isopropylidene-a-D-mannofuranose (26) (Scheme 5). The oxime 27, prepared from 26, underwent reduction by hydrogenation in the presence of Raney nickel, and subsequent removal of the trityl group afforded the amines 28 and 29. Acid hydrolysis of 28 afforded 30 (21%), which was converted to 31 (28%) that upon treatment with Dowex 1 (OH ) resin afforded 1. On the other hand, hydrogenation of 28 gave 32, which upon removal of the... 

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