Aminals, preparation

In addition to the nitrile and alcohol routes for fatty amine preparation, processes have been described by Unocal and Pennwalt Corporation, using an olefin and secondary amine (14—16) by Texaco Inc., hydrogenation of nitroparaffins (17—20) by Onyx Corporation, reaction of an alkyl haUde with secondary amines (21,22) by Henkel Cie, GmbH, reduction of an ester in the presence of a secondary amine (23) by catalytic hydroammonolysis of carboxyhc acids (24) and by the Hofmann rearrangement (25). 

The SEM derivative of a secondaiy aromatic amine, prepared from SEMCl (NaH, DMF, 0°, 100% yield), can be cleaved with HCl (EtOH, >88% yield). ... 

The in-out bicyclic amines prepared by Simmons and Park bear a remarkable semblance to the cryptands but lack the binding sites in the bridges. As a result, these molecules interact with electrophiles in a fashion similar to other tertiary amines and generally do not exhibit strong interactions with alkali or alkaline earth metal ions. The in-out bicyclic amines are prepared by reaction of the appropriate acid chlorides and amines in two stages to yield the macrobicyclic amine after reduction of the amidic linkages. A typical amine is shown above as compound 18. 

Originally, a C-20 amine (prepared from a bisnorcholanic acid) was converted into its 7V-chloro derivative, dehydrohalogenated to the imine, converted into the A-acetylenanime, reacted with perbenzoic acid, then hydrolyzed to the 17a-hydroxy-20-ketone ... 

Amines, preparation from isothiocyanates, 18, 5 from ketones, 17, 76 m-Aminobenzaldehyde, 13, 28... 

The electrochemical behaviour of silyl-substituted nitrogen compounds is also interesting. The introduction of a silyl group at the carbon adjacent to the nitrogen of carbamates causes a significant decrease in the oxidation potentials, although such effect is much smaller for amines. Preparative electrochemical oxidation of silyl-substituted carbamates in methanol results in smooth and selective cleavage of the C Si bond and introduction of methanol at the a-... 

The most straightforward method for the synthesis of the sulfonamide class of 1,2-thiazines is the intramolecular amidation reaction between a sulfonyl chloride and an amine. Preparation of the sulfonyl chloride moiety via the oxidation of thiol acetate 179 and subsequent deprotection and cyclization afforded sulfonamide 180, an intermediate for the synthesis of the matrix metalloproteinase inhibitor 38 (Scheme 22) <2004JME2981>. 

Contraindications Cerebrovascular accident (CVA), ischemicheart disease (including angina pectoris, history of Ml, silent ischemia, and Prinzmetal s angina), severe hepatic impairment, transient ischemic attack, uncontrolled hypertension, use within 14 days of MAOls, use within 24 hr of ergof amine preparations... 

The absolute configuration of all chiral amines prepared was determined by comparison with literature rotation values to be S. The (S)-enantiomers possess a positive rotation and the derived a-naphthamides elute, as in other cases, after the (//(-enantiomer on a chiral Pirkle column. 

Preparation of the complex. The solution of bis[2-(hydroseleno)ethyl]methyl-amine prepared above is gradually added to a solution of nickel acetate tetrahydrate (4.32 g, 17.4 mmole) in ethanol (100 mL) and stirred for 1 h. The solvent is removed under reduced pressure to obtain a dark mass, which is extracted with benzene (10 x 80 mL). These green extracts are combined, and the benzene is removed under vacuum. The resulting solid is washed with 10 mL of methanol and 50 mL of ether and dried in vacuo to obtain the desired product. Yield = 2.01 g (38.2%). 

The amines prepared are summarised in Tables 1 and 2. Of the materials tested, those based on primary amines were by far the most active, and were capable of converting a range of ketones to condensation products in excellent yields and selectivity in relatively short times. Even the difficult substrate acetophenone reacted to a significant extent (Table 5)... 

Few examples of the preparation of hydrazines or hydroxylamines on insoluble supports have been reported (Table 10.17). Hydrazines have been prepared by the reduction of aromatic diazonium salts or /V-nitroso amines (prepared from secondary amines by treatment with tert-butyl nitrite [340]), and by the N-amination of support-bound amines (Entry 3, Table 10.17). The direct reduction of hydrazones with borane to yield hydrazines on solid phase has not been reported, and appears to be difficult because of the ease with which the N-N bond of hydrazines is cleaved by reducing agents [340]. 

The heterogeneous catalytic hydrogenation of nitriles has been used in amine preparation for a long time. Generally the products are a mixture of primary, secondary and tertiary amines, the nature of which depends on the catalyst used as well as on reaction conditions (refs. 1,2). The selectivity of nitrile hydrogenation is of importance, particularly in the production of primary amines. In such reactions the catalysts most often proposed are Raney nickel catalysts (refs. 1-3). 

TERTIARY AMINE PREPARATION BY REDUCTIVE ALKYLATION OF ALIPHATIC SECONDARY AMINES WITH KETONES... 

Exercise 23-24 Show how a mixture of amines prepared from 1-bromobutane and an excess of butanamine may be resolved into its components by reaction with the anhydride of 1,4-butanedioic acid, (CH2)2(CO)20, separation of the products through advantage of their solubility properties in acid or base, and regeneration of the corresponding amines (Section 18-10C). Write equations for the reactions involved. 

Amines are saturated, nitrogen-containing functional groups that are widely encountered. Because the nitrogen atom of amines is basic, nucleophilic, and oxidizable, some constraints on the preparation of amines result. A collection of textbook amine preparations includes the following ... 

Table I. Optically Active Carbonyl Compounds and Amines Prepared by Asymmetric Synthesis Using the SAMP/RAMP Hydrazone Method... 

Borane—l-alkylimidazol-2-ylidenes, preparation, 6, 163 Borane—amines, preparation, 9, 149—150... 

The moderate yield may be due to the purification by reverse-phase chromatography, because 1 contains a tertiary amine. Preparation of other derivatives of 2 has shown that the radical annulation normally proceeds with 50-60 % yield and that many functional groups are tolerated (free alcohols, amines, esters, chlorides and terminal alkenes). Also (Me3Si)4Si may be a useful substitute for hexamethylditin, because tin residues are toxic and difficult to separate from the products. 

Method A. l-Benzo[b]thien-2-yl ethyl hydroxyl amine prepared as described above, step 3 (2.0 g, 10 mmole), was refluxed for 30 minutes with trimethylsilyl isocyanate (1.65, 14.2 mmole) in dioxane (30 ml). The reaction mixture was then washed with saturated NH4CI solution, dried with MgS04, and evaporated. 

Method B. l-Benzo[b]thien-2-yl ethyl hydroxyl amine prepared as described in step 3, was dissolved in toluene (100 ml) and HCI gas was bubbled through the mixture at a moderate rate for about 4 minutes. The solution was then heated to reflux and phosgene was bubbled through for another 4 minutes. After an additional one hour reflux, the mixture was allowed to cool to room temperature and then added to excess cold ammonium hydroxide solution. 

The ultraviolet spectra 27,28 exhibit, in agreement with the general postulate of Braude et al.2%-30 a bathoehromic shift to 225-235 m/j. caused by the auxochromic action of the nitrogen-free electron pair. This shift is approximately the same as that caused by introduction of a conjugated double bond, and is increased by further conjugation with other multiple bonds, e.g. in diene-amines prepared from A -3-oxosteroids.31,32 Spectral maxima (at 280-285 mfi, e 19,000-26,000) point to the conjugation of three mobile electron pairs but cannot decide the position of the double bonds the molecular extinction coefficient indicates a transoid (5) rather than cisoid arrangement (e.g. 6).33... 

A Diels-Alder approach to varenicline was recently published by Dr. Reddy s Laboratories. Entry to a key bicyclic intermediate is achieved by an iodide-catalyzed Diels-Alder reaction of tetrabromo dimethyl pyrazine (47) with excess norbomadiene. Dihydroxylation of 48, oxidative cleavage, and reductive amination prepares N-p-methoxybenzyl varenicline (50), which is deprotected under transfer hydrogenation conditions to give varenicline (1) in 10% yield for the sequence.47 This approach continues the theme of building the piperidine of 1 through olefin oxidative cleavage and reductive amination, but by doing so late in the sequence however, the approach... 

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