Imines, and

Primary and secondary amines also react with epoxides (or in situ produced episulfides )r aziridines)to /J-hydroxyamines (or /J-mercaptoamines or 1,2-diamines). The Michael type iddition of amines to activated C—C double bonds is also a useful synthetic reaction. Rnally unines react readily with. carbonyl compounds to form imines and enamines and with carbo-tylic acid chlorides or esters to give amides which can be reduced to amines with LiAlH (p. Ilf.). All these reactions are often applied in synthesis to produce polycyclic alkaloids with itrogen bridgeheads (J.W. Huffman, 1967) G. Stork, 1963 S.S. Klioze, 1975). 

Enamines derived from ketones are allylated[79]. The intramolecular asymmetric allylation (chirality transfer) of cyclohexanone via its 5-proline ally ester enamine 120 proceeds to give o-allylcyclohexanone (121) with 98% ee[80,8l]. Low ee was observed in intermolecular allylation. Similarly, the asymmetric allylation of imines and hydrazones of aldehydes and ketones has been carried out[82]. 

Carbinolamines are formed by nucleophilic addition of an amine to a carbonyl group and are intermediates in the for mation of imines and enamines Carbocation (Section 4 8) Positive ion in which the charge re sides on carbon An example is tert butyl cation (CH3)3C Carbocations are unstable species that though they cannot normally be isolated are believed to be intermediates in certain reactions... 

Quinones are exceptions. When one or more atoms of quinonoid oxygen have been replaced by >NH or >NR, they are named by using the name of the quinone followed by the word imine (and preceded by proper affixes). Substituents on the nitrogen atom are named as prefixes. Examples are... 

Imines and oximes Aliphatic a,/3-Unsaturated and aromatic Conjugated cyclic systems 1690-1640 (w) 1650-1620 (m) 1660-1480 (var) 960-930 (s) NO stretching of oximes... 

Benzophenone Process. Benzophenone, (CgH5 )2C=0, reacts with ammonia to form diphenylmethanimine, (CgHg )2C=NH. In the presence of copper catalysts, this is oxidized with oxygen to benzophenone azine, (CgHg )2C=N—N=C(CgHg The formation of the imine and its... 

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). 

Dipolar cycloaddition reactions with azides, imines, and nitrile oxides afford synthetic routes to nitrogen-containing heterocycles (25—30). 

The first-order decomposition rates of alkyl peroxycarbamates are strongly influenced by stmcture, eg, electron-donating substituents on nitrogen increase the rate of decomposition, and some substituents increase sensitivity to induced decomposition (20). Alkyl peroxycarbamates have been used to initiate vinyl monomer polymerizations and to cure mbbers (244). They Hberate iodine quantitatively from hydriodic acid solutions. Decomposition products include carbon dioxide, hydrazo and azo compounds, amines, imines, and O-alkyUiydroxylarnines. Many peroxycarbamates are stable at ca 20°C but decompose rapidly and sometimes violently above 80°C (20,44). 

Amin omethyl-3,5,5-trimethyl cyclohexyl amine (21), commonly called isophoronediamine (IPD) (51), is made by hydrocyanation of (17) (52), (53) followed by transformation of the ketone (19) to an imine (20) by dehydrative condensation of ammonia (54), then concomitant hydrogenation of the imine and nitrile functions at 15—16 MPa (- 2200 psi) system pressure and 120 °C using methanol diluent in addition to YL NH. Integrated imine formation and nitrile reduction by reductive amination of the ketone leads to alcohol by-product. There are two geometric isomers of IPD the major product is ds-(22) [71954-30-5] and the minor, tram-(25) [71954-29-5] (55). 

Reductions of Nitriles. In the reduction of nitriles, hydrogen is added progressively across the carbon—nitrogen triple bond, forming first the imine and then the amine. 

The tertiary amine is formed in a similar manner from the imine and a secondary amine. This side reaction can be minimized by carrying out the hydrogenation in the presence of ammonia, which tends to shift the equiHbrium back towards the imine. When a compound with two or more nitrile groups is hydrogenated, the formation of both cycHc and acycHc secondary and tertiary amines is possible, depending on whether the side reaction is intramolecular or intermolecular. For example, for the hydrogenation of adiponitfile ... 

A/ -Methoxycarbonyl-2-pyrroline undergoes Vilsmeier formylation and Friedel-Crafts acylation in the 3-position (82TL1201). In an attempt to prepare a chloropyrroline by chlorination of 2-pyrrolidone, the product (234) was obtained in 62% yield (8UOC4076). At pH 7, two molecules of 2,3-dihydropyrrole add together to give (235), thus exemplifying the dual characteristics of 2,3-dihydropyrroles as imines and enamines. The ability of pyrrolines to react with nucleophiles is central to their biosynthetic role. For example, addition of acetoacetic acid (possibly as its coenzyme A ester) to pyrroline is a key step in the biosynthesis of the alkaloid hygrine (236). 

The first /3 -lactam was produced by addition of a ketene to an imine and there are now many examples of this type of approach. The ketenes are most frequently generated in situ from acid chlorides by dehydrohalogenation, but have also been produced from diazo ketones, by heating of alkoxyacetylenes and in the case of certain cyanoketenes by thermolysis of the cyclic precursors (162) and (163). 

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

Peptide synthesis via a three or tour component condensation (amino acid, imine and bocyanide)... 

Secondary amines cannot form imines, and dehydration proceeds to give carbon-carbon double bonds bearing amino substituents (enamines). Enamines were mentioned in Chapter 7 as examples of nucleophilic carbon species, and their synthetic utility is discussed in Chapter 1 of Part B. The equilibrium for the reaction between secondary amines and carbonyl compounds ordinarily lies far to the left in aqueous solution, but the reaction can be driven forward by dehydration methods. 

Lithium aluminum hydride (LiAlH4) is the most powerful of the hydride reagents. It reduces acid chlorides, esters, lactones, acids, anhydrides, aldehydes, ketones and epoxides to alcohols amides, nitriles, imines and oximes to amines primary and secondary alkyl halides and toluenesulfonates to... 

The chapter is divided into three sections, devoted to the discussion of the synthesis of (1) oxiranes (epoxides), (2) aziridines (ethylene imines) and (3) thiiranes (episulfides). 

The free 17j8-amine can be transformed to the 17-ketone by chlorination to the iV-chloroamine, dehydrohalogenation to the imine, and finally hydrolysis.While these latter steps proceed in reasonable yield, the overall sequence does not compare well in efficiency with the process starting with a A -20-keto steroid ... 

Carbon-nitrogen multiple bonds in fluorinated imines and nitriles react with halogen fluoride reagents Imines provide 7V-chloroamine.s on reaction with chlo rme fluoride [62, 121, 122, 123] (equations 23 and 24) or with cesium fluoride and chlorine [124] and A -bromoammes on reaction with cesium fluoride and bromine (equation 24)... 

Trifluoromethyl-substitutedazimines are surprisingly stable compounds. They are accessible by 1,3-dipole metathesis from tnfluoromethyl-substituted azomethine imines and certain nitroso compounds [187, 188] On photolysis, an electrocyclic ring closure first gives the triaziridines, which are stable at room temperature. On heating above 80-100 C, a valence tautomenzation takes place and azimines are formed [189] (equation 43). 

A class of nitrogen-containing compounds that was omitted from the section just discussed includes imines and their- derivatives. Irnines are formed by the reaction of aldehydes and ketones with ammonia. Imines can be reduced to primary amines by catalytic hydrogenation. 

Carbinolamines are formed by nucleophilic addition of an amine to a carbonyl group and are intermediates in the formation of imines and enamines. 

In contrast to the five-membered ring, conformational factors would be expected to influence the equilibrium between the imine and enamine forms in the case of the six-membered-ring piperideine derivatives (154). 

Is the second step of the overall reaction for R=Me (N-methylphthalimide + hydrazine —> phthalimide hydrazide + methylamine) exothermic or endothermic Will higher temperatures accelerate or inhibit the reaction Is the structure drawn above for phthalimide hydrazide its lowest-energy form or are either the imine or diimine tautomers preferred Compare energies for the hydrazide and imine and diimine tautomers. Examine the geometry of phthalimide hydrazide and any low energy tautomer, and draw the Lewis structure(s) that best describes it. Can your Lewis structures account for the energy differences Examine electrostatic potential maps for all three molecules. Which molecule(s) are stablized by favorable electrostatic interactions Which are destabilized Can this help explain the energy differences Elaborate. 

Condensation between aldehyde 40 and amine 29 followed by sodium borohydride reduction of the resultant imine and cyclisation yielded isoquinoline 41 in good yield. Cyclisation occurred exclusively at the more electron-rich aromatic group. 

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