Imines, preparation from nitriles

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]. 

Recently, we have studied the addition of organometallic compounds to aluminum-imines and silylimines which are easily prepared from nitriles and aldehydes ly treatment with diisobutyl aluminum hydride (DIBAH) and lithium hexamethyl disilyl... 

However, when the addition is performed 111 a nucleopliilic solvent such as methanol, cleavage of the imine linkage occurs to give difliioroamino compounds [78] (equation 12) W, At-Difluorotrifluoromethylamine can be prepared from or from thiocyanates, as shown in equation 13 [79, 80] Another way to produce difluoroamino compounds is the addition of fluorine to nitriles by means of AgFj [Sf ] or C0F3 [S/]... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Highly functionalized tetraaryl-4,5-dihydro-l,2,4-triazoles 118a-y have been prepared on a soluble polymer support (PEG4000) from the cycloaddition of diarylimines with a nitrile imine, prepared in situ from the arylhydra-zone 119. The triazole products are highly fluorescent and several have reasonable fluorescence quantum yields (Scheme 8 and Table 19) <2005S3535>. 

The niobium imines can also be prepared by reaction of a niobium halo hydride with a nitrile. Thus a niobium reagent prepared from 1 and Bu3SnH reacts with nitriles to form a niobium-imido complex, which is hydrolyzed to a v/c-diamine. 

In recent work, a homochiral substituent has been incorporated into the reactant to allow the separation of enantiomerically pure products. Thus, the homochiral reactant 288, prepared from (5)-1-phenylethylamine, gave a pair of diastereoisomers (289) and (290) that were separated by chromatography and identified via X-ray crystallography (178). The nitrile imine was generated by the hydrazonyl chloride-base route. The reaction showed only modest stereoselectivity that favored 289 when silver carbonate was used as the base but it was found that this was reversed when triethylamine was used. However, this was not the case for a related reaction (179). 

The mesoionic compounds known as sydnones serve as cyclic azomethine imines. Thus, sydnone (167), isolable after preparation from die corresponding nitrosamine, underwent cyclization as an azomethine imine at 20-35 C (Scheme 52).86 Photolysis of sydnones also results in cyclization but through nitrile imine intermediates vide infra). 

Indoles have been prepared from reactions of o-aminophenylketones with reactive , or stable " arsonium ylides. Oxo-stabilized ylides reacted with 2-chloro-oximes to give trans-5-acyl-A -isoxazolines, and isoxazoles have been obtained from reactive arsonium ylides and a-isonitrosoketones, and from triphenylarsonium methylide and nitrile oxides The latter ylide reacts similarly with nitrile imines to give pyrazoles. With triphenylarsonium benzylides and benzoylylides,benzene diazonium salts give 1,3,4,6-substituted 1,4-dihydro-1,2,4,5-tetrazines in a reaction in which initial coupling of the reagents is followed by a dimerisation. ... 

The aforementioned D-galactose-derived chiral imines 27 were used for the Strecker synthesis of D-a-amino nitriles and D-o -amino acids by the Kunz group. Various types of glycosylim-ines 27, prepared from 2,3,4,6-tetra-0-pivaloyl-/3-D-galacosylamine with aliphatic or aromatic aldehydes, were treated with TMSCN in the presence of SnCl4, providing a-amino nitriles... 

The present methods for the preparation of N acyl a arylenamides include (i) reductive acylation of ketoximes with iron metal [2] or phosphines [3] in the presence of acyl chlorides or acyl anhydrides (Method A) (ii) metal catalyzed coupling of vinyl halides [4], triflates [5], or tosylates [6] with amides (Method B) (iii) reaction of imine intermediates derived from nitriles with acyl chlorides or anhydrides (Method C) [7] and(iv) Pd catalyzed coupling ofaryl tosylates with N acyl vinylamines (MethodD) [8]. 

Another route involving 1,3-dipoIar addition was next attempted (54). The key feature of this route is a cycloaddition of nitrile oxide (55) 88 with citraconate 87 (Scheme 16). Treatment of 89 prepared from 3-bromopropanol with phenyl isocyanate produced the nitrile oxide 88 which was then subjected to cycloaddition with dimethyl citraconate 87 to afford the adducts 86a and 86b as a 1 1 mixture. In this reaction, as expected, 86a, in which the less hindered oxygen is substituted at the quaternary carbon, was the major product (56). Conveniently, however, the undesired adduct 86b could be separated in the following dehydration step. These adducts were next subjected to various reduction conditions (57) in order to obtain intermediate 85 (eq.9). Unfortunately, we could not obtain any of the desired compound even under Curran s conditions (Raney-Ni (W-2), boric acid) which are mild enough to suppress undesired side reactions. All compounds produced in this reduction were retro-aldol products 90-93 probably derived from 85 or its imine form. This... 

The chemistry of azole X-oxides is relatively under developed compared, for example, with that of pyridine X-oxides, largely because of difficulty in their preparation from the azoles themselves. Some ring synthetic methods can be used, for example the reaction of 1,2-dicarbonyl mono-oximes with imines as shown. 1-Substituted imidazole 3-oxides can be converted into nitriles with loss of the oxygen using trimethylsilyl cyanide, careful choice of solvent minimising a tendency for isomeric mixtures to be formed. ... 

The chromone imines (97), prepared from 3-formylchromone by treatment with p-anisidine or p-phenetidine, react smoothly with the nitrile imines (98), generated in situ from the corresponding hydrazonoyl halides in the presence of dry tnethylamine in chloroform to yield the 1 2 4-tri-... 

In conclusion, we have prepared, for the first time, chiral yV-aluminum- and N-trimethylsilyl imines starting from aldehydes and nitriles. These compounds represent interesting starting materials for the preparation of a variety of biologically active nitrogen containing compounds. 

A similar method was later applied to the solid-phase synthesis of pyrazoles. A library of 25 compounds was prepared from a Rink resin-bound vinyl sulfone and nitrile imines generated in situ from hydrazonoyl chlorides (Scheme 11.15). The pyrazoles were obtained as a mixture of regioisomers. 

Nitriles can be prepared from aldehydes by a two-step procedure that involves formation of an imine with NH2OH, followed by dehydration with SOCI2. Show the mechanism of the reaction. 

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitnles arises both from the reactivity of the C=N bond, and from the abiHty of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxyHc acids and esters, aldehydes, ketones, large-ring cycHc ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy pubHshed (10). 

Chlorosulfonyl isocyanate is an excellent alternative to alkaline cyanates ia the preparation of hydantoias from stericaHy hindered or labile amino nitriles (62). Imino derivatives similar to (18) can also be obtained by addition of sonitnles to imines followed by treatment with a cyanate (63). 

Ethoxymethylene- and aminomethylene-amino intermediates are also of use for preparation of 4-ones and 4-imines, e.g. (121) — (122) — (123) from o-aminopyridine esters (78KGS1671) and nitriles (e.g. 75JCS(P1)2182>. 

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