Amine and Ketone

So, how does this whole thing work It s as simple as it sounds. An alcoholic solution of nitromethane and MDP2P is dripped into a mass of amalgamated aluminum immersed in alcohol first reducing the nitromethane to methylamine, allowing the Schiff base of the amine and ketone to form which is then further reduced to the desired MDMA. 

Potassium carbonate (anhydrous). Has a moderate efficiency and capacity, forming the dihydrate. Suitable for an initial drying of alcohols, bases, esters, ketones and nitriles by shaking with them, then filtering off. Also suitable for salting out water-soluble alcohols, amines and ketones. Unsuitable for acids, phenols, thiols and other acidic substances. 

Extension of the hydration reaction to hydrogen peroxide has shown that stable peroxides are formed from enamines and the imonium salts derived from secondary amines and ketones (506,507). 

Protophilic solvents are substances such as liquid ammonia, amines and ketones which possess a high affinity for protons. The overall reaction taking place can be represented as ... 

Extensive study by several groups showed that Ar—X (X = I, Ts, Br, and Cl) can undergo coupling reactions with amine and ketones in the presence of a... 

Bromide is displaced more easily from (5) than chloride, The second of our two methods, Grignard attack on a nitrile (p T 107), is used here. The final amination is carried out by catalytic hydrogenat ion of a mixture of amine and ketone. 

The amines and ketones used in this study are shown in Table 17.1. Among the seven catalysts tested, one was a 5% Pd/C while two were 3% Pt/C prepared on different carbon supports. Same catalysts were then sulfided to various degrees as shown in Table 17.2 along with their designation. 

On the other hand, Kobayashi has developed a Bronsted acid-combined catalyst for aqueous Mannich-type reactions. Three-component Mannich-type reactions of aldehydes, amines, and ketones (e.g., benzaldehyde, p-anisidinc. and cyclohexanone) were efficiently... 

In the multimedia models used in this series of volumes, an air-water partition coefficient KAW or Henry s law constant (H) is required and is calculated from the ratio of the pure substance vapor pressure and aqueous solubility. This method is widely used for hydrophobic chemicals but is inappropriate for water-miscible chemicals for which no solubility can be measured. Examples are the lower alcohols, acids, amines and ketones. There are reported calculated or pseudo-solubilities that have been derived from QSPR correlations with molecular descriptors for alcohols, aldehydes and amines (by Leahy 1986 Kamlet et al. 1987, 1988 and Nirmalakhandan and Speece 1988a,b). The obvious option is to input the H or KAW directly. If the chemical s activity coefficient y in water is known, then H can be estimated as vwyP[>where vw is the molar volume of water and Pf is the liquid vapor pressure. Since H can be regarded as P[IC[, where Cjs is the solubility, it is apparent that (l/vwy) is a pseudo-solubility. Correlations and measurements of y are available in the physical-chemical literature. For example, if y is 5.0, the pseudo-solubility is 11100 mol/m3 since the molar volume of water vw is 18 x 10-6 m3/mol or 18 cm3/mol. Chemicals with y less than about 20 are usually miscible in water. If the liquid vapor pressure in this case is 1000 Pa, H will be 1000/11100 or 0.090 Pa m3/mol and KAW will be H/RT or 3.6 x 10 5 at 25°C. Alternatively, if H or KAW is known, C[ can be calculated. It is possible to apply existing models to hydrophilic chemicals if this pseudo-solubility is calculated from the activity coefficient or from a known H (i.e., Cjs, P[/H or P[ or KAW RT). This approach is used here. In the fugacity model illustrations all pseudo-solubilities are so designated and should not be regarded as real, experimentally accessible quantities. 

Mannich and related readions provide one of the most fundamental and useful methods for the synthesis of p-amino carbonyl compounds, which constitute various pharmaceuticals, natural products, and versatile synthetic intermediates.1271 Conventional protocols for three-component Mannich-type readions of aldehydes, amines, and ketones in organic solvents indude some severe side reactions and have some substrate limitations, espedally for enolizable aliphatic aldehydes. The dired synthesis of P-amino ketones from aldehydes, amines, and silyl enolates under mild conditions is desirable from a synthetic point of view. Our working hypothesis was that aldehydes could read with amines in a hydro-phobic reaction fidd created in water in the presence of a catalytic amount of a metal triflate and a surfactant to produce imines, which could then read with hydrophobic silyl enolates. 

Quite recently, not only Lewis adds, but also Bronsted adds were found to be effedive catalysts for the three-component Mannich-type reactions in water with the aid of a surfadant. For example, Akiyama and co-workers1301 have reported that a combination of HBF4 and SDS is effedive for the readions of aldehydes, amines, and silyl enolates. We have found that dodecylbenzenesulfonic add (DBSA), a Bronsted add with a surfadant moiety, also catalyzes the reactions in water.1311 Furthermore, DBSA can be used for the dired Mannich-type reactions of aldehydes, amines, and ketones, without using silyl enolates as nucleophilic components (Eq. 8).1321... 

K Manabe, S. Kobayashi, Mannich-Type Readions of Aldehydes, Amines, and Ketones in a Colloidal Dispersion System Created by a Bronsted Acid-Surfadant-Combined Catalyst in Water Org. Lett. 1999, 1, 1965-1967. 

Figure 5.9 Examples of derivatization reagents for the colourimetric detection of primary and secondary amines and ketones.

This paper discusses the need for more stringent catalyst requirements for the reductive alkylation of secondary to tertiary amines. We illustrate the major importance of steric factors, with respect to both the amine and ketone and discuss the relative effectiveness of several catalysts. One obtains excellent yields with the more reactive and unhindered ketone, such as cyclohexanone and acetone, and relatively unhindered secondary amines. 

This is an extremely efficient reagent and is rapid in its action. Phosphoric oxide is difficult to handle, channels badly, is expensive and tends to form a protective syrupy coating on its surface. A preliminary drying with anhydrous magnesium sulphate, etc., should precede its use. Phosphoric oxide is only employed when extreme desiccation is required. It may be used for hydrocarbons, ethers, alkyl and aryl halides and nitriles, but not for alcohols, acids, amines and ketones. 

Metabolism is almost always an oxidative process. Reductive metabolism is much more limited. Functional groups that are reduced are, naturally, in a higher oxidation state. The more common examples include nitro groups, which are reduced to amines, and ketones, which reduce to alcohols. Chloramphenicol (8.28), an antibiotic that has fallen out of favor because of serious side effects, contains a nitro group that is reduced to the corresponding amine (8.29) (Scheme 8.9).7 Warfarin (Coumadin, 8.30), an anticlotting agent, is at least partially metabolized by reduction of its ketone to an alcohol. 

Our second example is an amine structurally similar to the deadly nightshade drug, atropine, which has the ability to calm involuntary muscle movements. There is a 1,3-relationship between the amine and ketone functional groups, and 1,3-disconnection takes us back to piperidine and an unsaturated ketone. 

Figure 3. Map of a theoretical biological activity. The biological activity has been contoured against the structures arising from a particular combination of amine and ketone fragments. If at first the amine fragment is held constant (amine A) the ketone associated with maximal activity is 1. If the ketone is held constant as 1, the most potent amine is B, resulting in the false optimum B-l (in square). The true optimum C-3 (in hexagon) is never found.

Binding of Amines and Ketones to Bifunctional Lewis Acids... 

It is noted that the magnitude of the contact contribution varies considerably between the and resonances. In order to obtain structural information on the lanthanide complexes at least six Gj values are, in general, required (three polar coordinates to fix the position of the lanthanide ion relative to the molecule, two additional angles to define the main magnetic axis orientation, and one signed value for the proportionality constant). The six nuclei used to provide these Gj values need not necessarily be protons. In a later paper Reilley et al. (388) discuss certain refinements of their method and apply it to a wide variety of LSR complexes including those of water, pyridines, alcohols, anilines, aliphatic amines, and ketones. The contact contributions of the C shifts of Ln(DPA)3 and Ln(MDPA)3 complexes are found to be important even for carbons five bonds removed from the lanthanide ion. (390)... 

Such a sequence allows one to conclude that the insertion of a flexible spacer between the tertiary amine function and the main chain causes a sharp increase of photoinitiation efficiency. In addition, the relative distance of tertiary amine and benzophenone groups from the polymer chain appears to be quite an important structural requirement. Indeed, the above findings suggest that, provided the spacer is flexible, an improvement of activity is observed when both amine and ketone moieties are located at similar distances from the backbone. 

DBU was also used in the (ert-butyldimethylsilylation of alcohols, phenols, mercaptans, thiophenols, carboxylic acids, amines, and ketones with tcrt-butyldimethylchlorosilene in dichloromethane, benzene, or acetonitrile at room temperature or at 80°C (85TL475). Good chemoselecti vity was observed in the case of alcohol. The formation of primary silyl ethers was the quickest. 

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