Reducing cyclic amines

Perhaps the most reliable method for the reductive cyclization of a nitro ester to a hydroxamic acid is that which involves treatment with sodium horohydride in the presence of palladium on charcoal. Although under these conditions aromatic nitro compounds are reduced to amines, o-nitro esters such as 53, in which the ester group is suitably oriented with respect to the nitro group, give good yields of cyclic hydroxamic acids (54). Coutts and his co-... 

In order to overcome these two issues, we reversed the order of the reaction sequence, as summarized in Scheme 1.20. We took advantage of the alcohol functional group in 50. Oxidation ofpMB of 50 with DDQ proceeded smoothly to form cyclic aminal 52 (as a mixture of a and P = 11.5 1) in toluene at 0-10 °C. The resulting DDQH, which is insoluble in toluene, was filtered off, and isolated DDQH could be recycled as we demonstrated in the Proscar process (see p. 92) [32]. Thus, this process minimizes the impact to the environment from an oxidizing reagent. Cyclic aminal 52 was solvolyzed with NaOH in MeOH at 40 °C. The resulted anisaldehyde was reduced in situ to pMBOH 43 by addition of NaBH4 and the desired amino alcohol 53 was isolated by direct crystallization from the reaction mixture, upon neutralization with acetic acid, in 94% yield and >99.9% ee after crystallization from toluene-heptane. 

Corrosion inhibitors are used to reduce the corrosion of surface equipment, surface casing, and the drill string by drilling and well treatment fluids. Many different corrosion inhibitors have been used. These include amine salts such as ammonium sulfite -bisulfite blends, zinc carbonate, zinc chromate, hydrated lime, fatty amine salts of alkylphosphates, cationic polar amines, ethoxylated amines, and tertiary cyclic amines. Commercial products are usually proprietary blends of chemicals. 

The reduction of imines and iminium salts present a particular difficulty in that those which are N-substituted can exist in different geometrical isomers that are reduced at different rates and with different selectivities. One way to overcome this problem is to use cyclic imines that can exist only as cis isomers. Although these are good substrates, this is not a general solution. The cyclic amines produced by transfer hydrogenation, together with best reported enantiomeric excesses, are listed in Table 35.6. Primary amines are difficult to pre-... 

Reduction reactions, which usually convert imine to secondary amine functions, are also metalion specific and usually most successful for the Ni" complexes. Reductions can be by electrochemical means or by chemical reductants such as NaBH4, NiAl/OH, H2/Pt or H2/Ni. H3P02 is specific for conversion of an a-diimine group to a monoimine. Examples of imine complexes which have been reduced to form cyclic amine complexes include (1), (3), (4), (9), (16) and (20). 

Several cyclic imines were reduced with phenylsilane as a reducing agent in the presence of the chiral titanocene catalyst 11 followed by a workup process to give the corresponding cyclic amines in excellent ee [26]. The hydrosilylation of 2-propyl-3,4,5,6-tetrahydropyridine with (R)-ll (substrate Ti=100 l) in THF at room temperature was completed in about 6 h (Scheme 14) [29]. The reaction mixture was treated with an acid and then with an aqueous base to afford (S)-coniine, the poisonous hemlock alkaloid, in 99% ee. 

A neutral Ir complex consisting of [IrCl(COD)]2 and (S)-6 catalyzed the hydrosilylation of the N-methylimine of acetophenone (substrate Ir=100 l) with two equivalents of diphenylsilane in ether at 0 °C to give the S product in 89% optical yield (Scheme 17) [34]. The corresponding N-phenylimine was reduced with 23% optical yield. 2-Phenyl-1-pyrroline was reduced with the same catalyst to afford the S cyclic amine in 88% ee. The enantiomeric excess was decreased to 7% in the hydrosilylation of the corresponding 6-membered cyclic imine. 

Catalytic reduction of the nitro group gives the amine 79 that cyclises instantly (chapter 7) to the imine 80 reduced in its turn to the cyclic amine 81. When the virtually planar five-membered ring of the imine settles on the surface of the Pd/charcoal catalyst it can choose between the side of the ring with a hydrogen atom or the side with the butyl group. It chooses the less hindered side and so the second hydrogen atom is cis to the first and the stereochemistry is correct (compare 81 with 71). 

Marcus treatment does not exclude a radical pathway in lithium dialkyl-amide reduction of benzophenone. It does, however, seem to be excluded (Newcomb and Burchill 1984a,b) by observations on the reductions of benzophenone by N-lithio-N-butyl-5-methyl-l-hex-4-enamine in THF containing HMPA. Benzophenone is reduced to diphenylmethanol in good yield, and the amine yields a mixture of the acyclic imines no cyclic amines, expected from radical cyclization of a putative aminyl radical, were detected. An alternative scheme (17) shown for the lithium diethylamide reduction, accounts for rapid formation of diphenylmethoxide, and for formation of benzophenone ketyl under these conditions. Its key features are retention of the fast hydride transfer, presumably via the six-centre cyclic array, for the formation of diphenylmethoxide (Kowaski et al., 1978) and the slow deprotonation of lithium benzhydrolate to a dianion which disproportion-ates rapidly with benzophenone yielding the ketyl. The mechanism demands that rates for ketyl formation are twice that for deprotonation of the lithium diphenylmethoxide, and, within experimental uncertainty, this is the case. 

Another general method for the introduction of a nitrogen atom into a macrocyclic skeleton is via the Beckmann reaction. Rearrangement of cyclotridecanone oxime led to cyclic lactam, which was reduced to amine by lithium aluminium hydride (LAH). Further substitution yielded 14-membered mutuporamine <1999TL5401>. Dieckmann condensation was used for the preparation of 14-membered aza ketone 15 <1999JA2919>, but no experimental details were given. 

The results show that the presence of bulky substituent on a polymer chain may effectively inhibit the termination proceeding by this mechanism. The results presented at this point may be summarized as follows chain transfer to polymer is a general feature of cationic ring-opening polymerization although for different systems the contribution of this reaction may vary only in some systems this process results in termination (These systems involve, e.g., cyclic amines (3- and 4-membered) and cyclic sulfides (3- and 4-membered) and the contribution of the reaction is reduced for substituted chains. 

Sodium (5)-prolinate-borane complex (104) reduces cyclic imine (105) to give the (S)-tetrahydroiso-quinoline derivative (106) in 87% ee. Related amines (107) and (108) are also prepared in a like manner in 86% ee and 11% ee, respectively. - ... 

In macroscale electrolyses, lactams or fully saturated cyclic amines are obtained in good yields from imides in strongly acidic electrolytes [1-5] for example, 7V-methylsucci-nimide is reduced in good yield to A -methylpyrrolidone at a lead cathode in sulfuric acid solution [140]. 

C-Substituted cyclic amines have been prepared by reduction of substituted amide (oxo) azama-crocycles, usually with B2H6/thf. 6R-5,7-Dioxo-cyclams (80) prepared by reaction of 2,3,2-tet with substituted malonic esters, i -CH(COOEt)2, reduce to form 6i -cyclams (81) (R = Ph, 2-ethylpyr-idyl, alkyl, benzyl, -(CH2)2OH, etc.) (Scheme 20).73... 

The nitrogen atoms of cyclic amines are readily substituted by reaction with nucleophiles (usually alkyl halides in base), or with Michael acceptors (usually acrylic compounds). A variety of TV-substituted cyclams, e.g., (54), (57), and homologues, has been prepared by reducing substituted dioxo cyclams (53) and (56). TV-Functionalization can be introduced for precursors before cyclization, e.g., (20), (24), (52), and (55), and the azacyclam macrocycles (74)-(79). 

Many reactions that produce specific numbers and/or distributions of TV-substituents, or combinations of different TV-substituents, have been devised. The protecting groups boc (t-butyl-oxycarbonyl)104 and trityl (triphenylmethyl)105 are convenient since they can be removed under mild conditions. C-Substitution can alter the relative reactivity of nitrogen atoms by steric or inductive effects to determine substitution patterns (e.g., for the bis(l,2-cyclohexdiyl) cyclam (23), which preferentially bis-substitutes at the six and 16 sites).101 The presence of imine or amide functions also determine substitution patterns and the substituted imine or amide macrocycles can be reduced to the substituted cyclic amine. 

Cyclic amines react with oxetane or 3-bromo-l-propanol to introduce 3-hydroxypropyl TV-substituents. The compounds show reduced formation constants compared with the hydroxy-ethyl compounds and the OH groups show little tendency to coordinate.123... 

Addition of acrylonitrile to cyclic amines yields the per-7V-(2-cyanoethyl)-substituted macrocycles,124 which can be reduced to form the 2-aminopropyl compounds,125 or hydrolyzed to form the 2-carbamoylethyl compounds.126 Pendant nitrile groups coordinate only weakly. 

Bridged or reinforced azamacrocycles, which have pairs of nitrogen atoms of an aza-macrocycle linked, usually by an a,cu-alkandiyl bridge, 154 are prepared by reaction of a cyclic amine with a bifunctional nucleophile, such as an a,cu-dibromoalkane or an a,cu-ditosyl-alkane-diol. Bis(acyl esters), amides, and halides react with amines to form bicyclic amides which can be reduced to the bicyclic amines.155 The bridge can have internal functions, such as C=C or o-C6H4 (or include hetero atoms, thus forming clathrochelates).156... 

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