Ammonia alkyl halides

With the use of these sensitivity-enhancement approaches the stable alkoxide intermediates were indeed detected by C CP/MAS NMR spectroscopy. Isopropoxide was the first alkoxy intermediate reliably identified in propylene labeled with C in the CH= group) conversion on zeolite HY [15]. Isopropoxide exhibits the signal at 87 ppm from the labeled C atom, which is characteristic of the (CH3)2CH fragment bonded to an oxygen atom of the zeolite framework (Fig. 20). Later, other alkoxide intermediates were detected and characterized. It was demonstrated that methoxides [121,122] and ethoxides [122,123] formed from methyl and ethyl iodides and also from methanol and ethanol on H-ZSM-5 and CsX zeolites. Isobutoxy [124] and tert-butoxy [90] intermediates resulted from the dehydration of isobutanol and tert-butanol on HZSM-5. Alkoxides are highly reactive species. For example, surface methoxides are effective methylating agents in their reactions with methanol, water, ammonia, alkyl halides, HCl, CO, acetonitrile, and aromatic compounds [125]. 

The preparation of pure primary amines by the interaction of alkyl halides and ammonia is very difficult, because the primary amine which is formed reacts with unchanged alkyl halide to give the secondary amine the latter... 

Although this reaction is useful for preparing a ammo acids (Table 22 3 fifth entry) it IS not a general method for the synthesis of amines Its major limitation is that the expected primary amine product is itself a nucleophile and competes with ammonia for the alkyl halide... 

Because alkylation of ammonia can lead to a complex mixture of products it is used to prepare primary amines only when the starting alkyl halide is not particularly expensive and the desired amine can be easily separated from the other components of the reaction mixture... 

A method that achieves the same end result as that desired by alkylation of ammonia but which avoids the formation of secondary and tertiary amines as byproducts is the Gabriel synthesis Alkyl halides are converted to primary alkylamines without contam mation by secondary or tertiary amines The key reagent is the potassium salt of phthal imide prepared by the reaction... 

The reaction of amines with alkyl halides was seen earlier (Section 22 7) as a complicat ing factor in the preparation of amines by alkylation of ammonia... 

Ammonia can act as a nucleophile toward primary and some secondary alkyl halides to give primary alkylamines Yields tend to be modest because the primary amine IS itself a nucleophile and undergoes alkylation Alkylation of ammonia can lead to a mixture containing a primary amine a secondary amine a tertiary amine and a quaternary ammonium salt... 

A number of 2eohtic materials have been claimed to cataly2e this reaction and reaction temperatures are on the order of 200—350°C with pressures as high as 18000 kPa (2600 psi) reported. This is a low conversion process and recycle of the unconverted starting materials is necessary to provide an economical process. Amination of ethylene to produce ethylamines cataly2ed by ammonium iodide is reported, but not beheved to be practiced commercially (15,16). Alkyl Halide Amination (Method 7). The oldest technology for pioducing amines is the reaction of ammonia with an alkyl hahde. This... 

The amines are a group of compounds with the general formula R-NHj, and all the common amines are hazardous. As a class the amines pose more than one hazard, being flammable, toxic, and, in some cases, corrosive. The amines are an analogous series of compounds and follow the naming pattern of the alkyl halides and the alcohols that is, the simplest amine is methyl amine, with the molecular formula of CH NHj. Methyl amine is a colorless gas with an ammonia-like odor and an ignition temperature of 806°F. It is a tissue irritant and toxic, and it is used as an intermediate in the manufacture of many chemicals. Ethyl amine is next in the series, followed by propyl amine, isopropyl amine, butyl amine and its isomers, and so on. 

Weiss ° treated 16-dehydro- (6), 17a-acetoxy- (8), 17a-hydroxy- (9) and 17a-bromopregnan-20-one (11) with a solution of lithium, barium, calcium or sodium in liquid ammonia and reacted the intermediate enolate anion (7) with the appropriate alkyl halide. 

Most of the alkylations were carried out by adding a solution of 3,3-ethylenedioxypregna-5,16-dien-20-one in tetrahydrofuran to a solution of lithium in liquid ammonia to the point of color discharge. Treatment with the alkyl halide then furnishes the corresponding 17a-alkyl derivative (10). After hydrolysis of the 3-ketal group, 17a-methyl-, ethyl-, propyl-, butyl-, hexyl-, octyl-, allyl-, and benzylprogesterones are obtained. 

Alkylamines are, in principle, capable of being prepared by nucleophilic substitution reactions of alkyl halides with ammonia. 

Reactions in liquid ammonia (cf. Chapter 3, Section III) require a certain amount of care, since the solvent is low boiling (—33 ) and its fumes are noxious. Nevertheless, with reasonable caution, the preparation of an ammonia solution of sodium acetylide can be carried out as described. The reagent so prepared can then be directly used for displacements on alkyl halides or for additions to suitable carbonyl compounds. Examples of both reactions are given. 

Ammonia and other amines are good nucleophiles in SN2 reactions. As a result, the simplest method of alkylamine synthesis is by Sn2 alkylation of ammonia or an alkylamine with an alky) halide. If ammonia is used, a primary amine results if a primary amine is used, a secondary amine results and so on. Even tertiary amines react rapidly with alkyl halides to yield quaternary ammonium salts, R4N+ X-... 

The reaction between alkyl halides and ammonia or primary amines is not usually a feasible method for the preparation of primary or secondary amines, since they are stronger bases than ammonia and preferentially attack the substrate. However, the... 

This fluorescent acid chloride can be used to form derivatives of alcohols, amines, and phenols. Using these fluorescent derivatives, an analysis of a series of n-alcohols from Ci to C4 was developed. A chromatogram produced by this technique is shown in Figure 3. Derivatives were also formed from ammonia, dimethylamine, and phenol. A derivative was formed from pentachlorophenol but was not fully characterized. The quantum yields of fluorescence of the alcohol derivatives of V were lower than those of the alkyl halide derivatives of III. 

Under the conditions of the Birch reduction, IV-Boc amides such as 60 can be reductively alkylated in high yields, presumably via a dianion intermediate which is protonated by ammonia at C-5 leaving an enolate anion at C-2 <96JOC7664>. Quenching the reaction with alkyl halides or ammonium chloride then affords the 3-pyrrolines 61. 

Organic derivatives of ammonia are called amines. Because nitrogen is trivalent, amines can be primary (attached to one carbon), secondary (attached to two carbons), or tertiary. All amines are basic, and their strength as bases increases with the number of alkyl groups attached to the nitrogen that is, methyl amine is a stronger base than ammonia and trimethylamine is stronger than dimethylamine. Amines can be prepared from ammonia and an alkyl halide ... 

Ammonia has always been the starting material for the synthesis of aliphatic amines. Thus, processes have been developed for the condensation of NH3 with alkyl halides (Hoffman reaction) or with alcohols in the presence of various catalysts. The latter reachon, first discovered by Sabatier in 1909 [8, 9] is nowadays the main method of industrial production of light amines (e.g. methylamines 600 000 t/yr) [5]. 

The three picolines react with alkyl halides in liquid ammonia solution in the presence of sodamide to yield the corresponding monoalkylpyridines. a-Picoline also reacts with alkyl chlorides in the presence of sodamide either alone or in the presence of xylene to give a fair yield of monoalkylpyridine CjH N.CHjR. With y-picoliue under similar experimental conditions disubstitution of the alkyl group (CjHjN.CHRj) occurs to an appreciable extent. The preparation of tile three n-amylpyridines is described the 3- and 4-compounds by the liquid ammonia - sodamide method and the 2-compound by the sodamide-3 ene procedure. 

A simple and atom-economical synthesis of hydrogen halide salts of primary amines directly from the corresponding halides, which avoids the production of significant amounts of secondary amine side products, has been described by researchers from Bristol-Myers Squibb [227]. Microwave irradiation of a variety of alkyl halides or tosylates in a commercially available 7 m solution of ammonia in methanol at 100-130 °C for 15 min to 2.5 h followed by evaporation of the solvent provided the corre-... 

The use of dimethyl sulphoxide as a dipolar aprotic solvent is well known,7 and the present method can be regarded as a model procedure and has been applied to the preparation of a number of N-w-alkyl-pyrroles and N-w-alkyl indoles.8 The yield of N-benzylindole is considerably higher than in previously reported preparations and is as good as that reported for the preparation of N-methylindole in liquid ammonia.4 The present method is, however, less laborious and quicker to carry out. Very high yields are obtained in reactions using w-alkyl halides and moderately good yields with secondary alkyl halides. The reactions should be compared with those recently reported for pyrryl-thallium.9... 

By heating an alkyl halide with an alcoholic solution of ammonia in a sealed tube, a mixture of amines is formed by nucleophilic substitution reaction. 

Good yields of 1° amines are obtained by using large excess of ammonia. The ammonolysis proceeds best by using primary alkyl halides. The tertiary alkyl halides tend to form alkenes due to the dominance of the competing elimination reaction. 

As esters the alkyl halides are hydrolysed by alkalis to alcohols and salts of halogen acids. They are converted by nascent hydrogen into hydrocarbons, by ammonia into amines, by alkoxides into ethers, by alkali hydrogen sulphides into mercaptans, by potassium cyanide into nitriles, and by sodium acetate into acetic esters. (Formulate these reactions.) The alkyl halides are practically insoluble in water but are, on the other hand, miscible with organic solvents. As a consequence of the great affinity of iodine for silver, the alkyl iodides are almost instantaneously decomposed by aqueous-alcoholic silver nitrate solution, and so yield silver iodide and alcohol. The important method of Ziesel for the quantitative determination of alkyl groups combined in the form of ethers, depends on this property (cf. p. 80). 

The two-electron reduction product of terephthalodinitrile reacts with alkyl halides in liquid ammonia to yield 4-alkylbenzonitriles and 2-alkylterephthalodinitriles. The product ratio strongly depends on the alkyl halide and changes in favour of the ipso product, 4-alkylbenzonitrile, on going from tertiary alkyl to primary and from iodide to chloride. This change is the result of increased contribution of the 5n mechanism relative to the ET mechanism. 

Alkyl vinyl tellurides can also be prepared by a sequential reaction of divinylic tel-lurides with lithium and alkyl halides in liquid ammonia. ... 

The most important reactions of alkyl substituents a and y to the ring heteroatom are those which proceed via base-catalyzed deprotonation. Treatment of 2- and 4-alkyl heterocycles with strong bases such as sodamide and liquid ammonia, alkyllithiums, LDA, etc., results in an essentially quantitative deprotonation and formation of the corresponding carbanions. These then react normally with a wide range of electrophiles such as alkyl halides and tosylates, acyl halides, carbon dioxide, aldehydes, ketones, formal-dehyde/dimethylamine, etc., to give the expected condensation products. Typical examples of these transformations are shown in Scheme 17. Deprotonation of alkyl groups by the use of either aqueous or alcoholic bases can also be readily demonstrated by NMR spectroscopy, and while the amount of deprotonation under these conditions is normally very small, under the appropriate conditions condensations with electrophiles proceed normally (Scheme 18). 

All acetylenes with a terminal triple bond are instantaneously converted into the alkali acetylides by alkali amides in liquid ammonia. For many alkylations with primary alkyl halides liquid ammonia is the solvent of choice and the functionalization with oxirane can also be carried out in it with good results. Reactions of ROOM with sulfenyladng agents (R SSR1, R SON, R SSC R ) or elemental sulfur, selenium or tellurium are mostly very successful in ammonia, the same holds for the preparation of ROC1 from RC=CM and iodine. The results of couplings with carbonyl compounds are very variable. 

Compared to many other types of synthetic intermediates, acetylides, RC=CM (M = Li, Na, K), show a moderate reactivity towards alkyl halides in the usual organic solvents E O and THF and in liquid ammonia [2], In this respect acetylides resemble enolates >C=COM. In the absence of dipolar aprodc co-solvents (DMSO or HMPT), lithium alkynylides, RC=CLi, react sluggishly in Et O or THF with most alkyl halides [2]. In liquid ammonia the alkylation of alkali acetylides with the lower (up to C-5) alkyl bromides or iodides proceeds at a satisfactory rate [5]. A certain amount of DMSO added to the reaction mixture increases the solubility of halides with a longer carbon chain. A second effect of the addition of this co-solvent is that the temperature of the reaction mixture can gradually rise as more ammonia evaporates. In this way, the reaction can proceed gradually over the range from -33 C (b.p. NH3) to room temperature. Specific alkylation on the acetylenic carbon takes place if an equivalent amount of an alkyl halide is added to dilithiated propargvl alcohol in liquid ammonia... 

For many alkylation reactions of alkynylides in liquid ammonia Li+ is preferred to both Na+ and K+ as counter-ion, since lithium alkynylides generally have a better solubility. Furthermore, the principal side-reaction, dehydrohalogenation of the alkyl halide, occurs to a lesser extent with lithium compounds. 

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