Imines preparation methods

Scheme 8.6 Known preparation method for cyclic imines.

Optically active oxaziridines are useful reagents for the enantioselective oxidation of olefins 37 39). The following three preparative methods to make this reagent available have been reported enantioselective oxidation of an imine by (-)-peroxycam-phoric acid 37,38), photocyclization of a nitrone which has a chiral substituent39), and photocyclization of a nitrone in an optically active solvent 39). However, an... 

Organomagnesium compounds react with imines, prepared from 3-methoxy-2-naphth-aldehydes by a 1.4-addition mechanism. This reaction can be performed with high diastere-oselectivity. The method was applied for the synthesis of optically pure S-tetralones . Vinyhnagnesium bromide reacts as an acceptor with a ketone dimethyl hydrazone zincate 207, yielding a 1,1-bimetallic species, which can be reacted sequentially with two different electrophiles (equations 131 and 132) . The reaction proceeds via a metalla-aza-Claisen rearrangement, where the dimethylhydrazone anion behaves as an aza-allylic system . 

Eight-membered heterocyclic systems embrace a very broad variety of compounds ranging from cyclic ethers and imines to highly labile analogs of cyclooctatetraene, and the properties and chemical behavior of these compounds of course depend entirely on the extent and location of unsaturation. For this reason, preparative methods and reactions are treated together for each ring system and oxidation level. 

The physical constants of several other imines prepared by a similar procedure are shown in Table X. The aldimines listed in the Table can be obtained only if certain precautions are strictly observed [4b]. The method of Emerson, Hess, and Uhle [4c] could not be extended satisfactorily and the method described in Preparation 2-2 is a modification of the one described by Chancel [4d] for propylidenepropylamine. The reaction is best carried out by adding the aldehyde to the amine, without a solvent, at 0°C. When the order of addition is reversed, the yields are much lower. Potassium hydroxide is added at the end in order to remove the water formed during the reaction. The use of other drying agents such as potassium carbonate or magnesium sulfate failed to yield aldimines on distillation. The aldimines should always be distilled from fresh potassium hydroxide to yield water-white products. The aldimines are unstable and should be used within a few hours after their distillation otherwise polymeric products are obtained. 

Sulfilimines and sulfoximines are useful synthetic building blocks for chiral ligands and pseudopeptides. Compared to other preparation methods, the direct imination of corresponding sulfides and sulfoxides is a more convenient and straightforward synthetic route. 

Preparative Methods the imine from (5)-alanine iV-methylamide and pivalaldehyde is cyclized by heating with benzoic anhydride to give mainly cis-(l) [(2/f,5S)-(l)] in modest yields alternatively, the imine cyclizes to the trans-substituted heterocycle by treatment with HCl in MeOH, and subsequent benzoylation produces trans-(l) [(25,55)-(l)] in high yield (eq 1). ... 

Preparative Methods the sodium salt of the pivalaldehyde imine of (S)-alanine is cyclized to the oxazolidinone by reaction with PhCOCl in CH2CI2 at low temperature the cis/trans ratio in the crude product depends upon the exact reaction conditions, it is usually 4 1 purification by a combination of crystallization and chromatography gives the pure cis derivative in 60-70% yield. Handling, Storage, and Precautions the solid material is stable for years when stored in a bottle. 

Preparative Methods the commercial glycine Wmethylamide hydrochloride is converted to the racemic imidazolidinone (2) by imine formation with Pivalaldehyde and cyclization under acidic conditions (eq 1). The mandelate salt of like configuration is less soluble and is used for highly efficient resolution subsequent treatment with Boc anhydride (Di-t-butyl Dicarbonate) gives the enantiomeric Boc-BMI (1) (eq 2). 

Preparative Methods (i) preparation of racemic DPEN and its optical resolution Reaction of benzil and cyclohexanone in the presence of ammonium acetate and acetic acid at reflux temperature gives a cyclic bis-imine (1) (eq 1). Stereoselective reduction of the bis-imine with lithium in THF-liquid ammonia at —78 °C followed by addition of ethanol, then hydrolysis with hydrochloric acid and neutralization with sodium hydroxide produces the racemic diamine (2). Recrystallization of the l-tartaric acid salt from a 1 1 water-ethanol mixture followed by neutralization with sodium hydroxide, recrystallization from hexane results in (5,5)-DPEN (3) as colorless crystals. 

Preparative Methods both enantiomers of the a-methyl sultam may be prepared on a multigram scale in optically pure form by asymmetric hydrogenation of imine (2a) followed by simple crystallization (eq 1). The (7 )-enantiomer of the a-f-butyl sultam may also be prepared in enantiomerically pure form by asymmetric reduction of imine (2b) followed by fractional crystallization. However, multigram quantities of either enantiomer of the a-t-butyl sultam may be prepared by derivati-zation of the racemic auxiliary (obtained in 98% yield from reaction of (2b) with Sodium Borohydride in MeOH) with 10-Camphorsulfonyl Chloride, separation of the resulting diastere-omers by fractional crystallization, and acidolysis. Prochi-ral imines (2a) and (2b) are readily prepared from inexpensive Saccharine by treatment with Methyllithium (73%) and t-Butyllithium (66%), respectively. 

The asymmetric catalytic reduction of ketones (R2C=0) and imines (R2C=NR) with certain organohydrosilanes and transition-metal catalysts is named hydrosilylation and has been recognized as a versatile method providing optically active secondary alcohols and primary or secondary amines (Scheme 1) [1]. In this decade, high enantioselectivity over 90% has been realized by several catalytic systems [2,3]. Therefore the hydrosilylation can achieve a sufficient level to be a preparative method for the asymmetric reduction of double bond substrates. In addition, the manipulative feasibility of the catalytic hydrosilylation has played a major role as a probe reaction of asymmetric catalysis, so that the potential of newly designed chiral ligands and catalysts can be continuously scrutinized. 

Nitrenes undergo addition reactions to neutral nucleophiles.60 51 Accordingly, they add to the nitrogen atom of pyridines, forming iV-imines. This method of preparation was described first by Curtius et a/.62-66 They heated aromatic sulfonyl azides in pyridine and obtained various A-sul-fonylimines [Eq. (5) ] the structures of which were not at that time recognized. They formulated sulfonyl nitrenes as intermediates in this reaction. 

Formation of several pyrazolyl-pyrazolino[60]fullerene adducts (45a-c) from nitrile imines by use of this procedure has been described (Scheme 21.17) [53, 54]. The nitrile imines are generated in situ from the corresponding hydrazone 42a-c and NBS in the presence of EtsN and then reacted with Ceo (1) under the action of microwave irradiation, using a focused microwave oven. The route is simpler than the previously described method, which involved cycloaddition of Qo to nitrile imines prepared from the corresponding N-chlorobenzylidene derivatives [55]. 

The oldest method for the formation of a ketene, used by Staudinger in his studies on diphenylketene, is the reduction of an a-haloacyl halide with activated zinc. Most often, the ketene components used in the Staudinger reaction are usually produced by either of two ways the elimination of an acyl chloride (or less frequently another activated carboxyl derivative) in the presence of a base, or the Wolff rearrangement of a-diazocarbonyl compounds.The ketene is usually generated in situ in the presence of the imine however, if the ketene is stable enough, it may be prepared separately and then introduced into reaction with the imine. Other methods to produce ketenes have been used less often in the Staudinger reaction due to incompatibility with the imine component or p-lactam product or due to the harsh conditions required, such as the high temperatures employed in the pyrolysis of acid anhydrides or ketone acylals. 

Several reviews on allylboron compoimds and odier allylmetal reagents and their additions to carbonyl compoimds and imines have appeared [1-6], including two excellent chapters in a book from Wiley-VCH [1,2]. Accordingly, diis chapter does not aim to provide a comprehensive accoimt on die chemistry of allylboronates, but presents instead an overview of die main preparative methods for allylboronates, with particular focus on advances reported in die past five years, and on several recent synthetic applications such as the Lewis add-catalyzed additions to carbonyl compounds and tandem allylation reactions. 

Hamasaki, M., Kimoto, K, and Yamamoto, H. (2011) Enzymic preparation method for optically active amine derivatives from imines by using imine reductase. JP 2011177029. 

Reactions with Amines and Amides. Hydroxybenzaldehydes undergo the normal reactions with aUphatic and aromatic primary amines to form imines and Schiff bases reaction with hydroxylamine gives an oxime, reaction with hydrazines gives hydrazones, and reactions with semicarbazide give semicarbazones. The reaction of 4-hydroxybenzaldehyde with hydroxylamine hydrochloride is a convenient method for the preparation of 4-cyanophenol (52,53). 

Bell and Hall have incorporated an organometallic unit into a crown by using the ferrocenyl unit as part of the ring or as a third strand. The unit is incorporated either as the 1,1 -diformylferrocene or the corresponding acid. In the former case, the bis-imine is prepared and reduced to give the saturated crown (see structure 24). In the latter case, the acid is converted into its corresponding chloride and thence into the diamide by reaction with a diamine. Diborane reduction affords the saturated amino-crown. Structure 24 could be prepared by either of these methods but the dialdehyde approach was reported to be poor compared to the amide approach which afforded the product in ca. 60% yield . 

The Bobbitt modification is the most widely used variation of the Pomeranz-Fritsch reaction. This modification involves cyclisation of benzylaminoacetal 10, usually prepared from the classical Pomeranz-Fritsch imine 9, to yield 4-hydroxy derivatives 11. The success of this method can be attributed to avoiding treatment and thus (partial) destruction of imine 10 under strongly acidic conditions. 

The Jackson modification involves cyclisation of iV-tosylated amine 12 and provides a complementary method to the classical Pomeranz-Fritsch reaction for entry into the fully unsaturated ring system 13. Amine 12 can be prepared from either the Pomeranz-Fritsch-Bobbitt imine 10 or reaction of benzylhalide 14 and the corresponding sodium anion 15. ... 

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