Secondary and Tertiary Amines

Special methods are available for particular classes of compounds, Hinsberg s method of separating primary, secondary and tertiary amines (p. 249)-... 

When the reaction is over, add- concentrated hydrochloric acid to decompose the tsocyanide and pour it away after the odour is no longer discernible. The test is extremely dehcate and will often detect traces of primary amines in secondary and tertiary amines it must therefore be used with due regard to this and other factors. 

Secondary and tertiary amines are not generally prepared in the laboratory. On the technical scale methylaniline is prepared by heating a mixture of aniline hydrochloride (55 parts) and methyl alcohol (16 parts) at 120° in an autoclave. For dimethylaniline, aniline and methyl alcohol are mixed in the proportion of 80 78, 8 parts of concentrated sulphuric acid are added and the mixture heated in an autoclave at 230-235° and a pressure of 25-30 atmospheres. Ethyl- and diethyl-anihne are prepared similarly. One method of isolating pure methyl- or ethyl-aniline from the commercial product consists in converting it into the Y-nitroso derivative with nitrous acid, followed by reduction of the nitroso compound with tin and hydrochloric acid ... 

Hinsberg procedure for the separation of primary, secondary and tertiary amines is given under (viii) above, and this method may be used. The following experimental details may, however, be found useful for the preparation of derivatives of primary and secondary amines. 

Secondary and tertiary amines are named as N substituted derivatives of primary amines The parent primary amine is taken to be the one with the longest carbon chain The prefix N is added as a locant to identify substituents on the ammo nitrogen as needed... 

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... 

Among compounds other than simple alkyl halides a halo ketones and a halo esters have been employed as substrates m the Gabriel synthesis Alkyl p toluenesul fonate esters have also been used Because phthalimide can undergo only a single alkyl ation the formation of secondary and tertiary amines does not occur and the Gabriel synthesis is a valuable procedure for the laboratory preparation of primary amines... 

Lithium Acetylide. Lithium acetyhde—ethylenediamine complex [50475-76-8], LiCM7H -112X01120112X112, is obtained as colodess-to-light-tan, free-flowing crystals from the reaction of /V-lithoethylenediamine and acetylene in an appropriate solvent (131). The complex decomposes slowly above 40°O to lithium carbide and ethylenediamine. Lithium acetyhde—ethylenediamine is very soluble in primary amines, ethylenediamine, and dimethyl sulfoxide. It is slightly soluble in ether, THF, and secondary and tertiary amines, and is insoluble in hydrocarbons. 

Sequential substitution reactions which transform alcohols into a family of primary, secondary, and tertiary amines. 

Secondary and tertiary amines are preferentially produced when rhodium or palladium are chosen as catalyst. As in Method 3, reforming reactions do not normally compete with the hydrogenation reaction and high selectivities to the desired product are possible. 

Symmetrical tertiary amines can be prepared in an analogous manner to secondary amines (1). Catalytic hydrogenation at elevated temperature and low pressure with a hydrogen purge produces a mixture of primary, secondary, and tertiary amines. 

To analy2e fatty amines, both wet and instmmental methods of analysis are used. Wet methods routinely used are total amine value (ASTM Method D2073) combining weight or neutralization equivalent primary, secondary, and tertiary amine content (ASTM Method D2083) moisture, Kad-Fischer (ASTM Method D2072) and iodine value, measure of unsaturation (ASTM Method D2075). These provide important information on physical and chemical characteristics of the amine products used in various appHcation areas (8,76,81). In addition to the ASTM methods available, the American Oil Chemists Society has developed methods of analysis for fatty amines (82). 

One characteristic of this reaction that can cause problems is that secondary and tertiary amines are produced in addition to the primary amine. It has been proposed that these side reactions occur through reaction of the imine iatermediate with the product amine, followed by the loss of ammonia and further hydrogenation (10). 

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 ... 

Nitrile Intermediates. Most quaternary ammonium compounds are produced from fatty nitriles (qv), which are ia turn made from a natural fat or oil-derived fatty acid and ammonia (qv) (Fig. 2) (see Fats AND FATTY oils) (225). The nitriles are then reduced to the amines. A variety of reduciag agents maybe used (226). Catalytic hydrogenation over a metal catalyst is the method most often used on a commercial scale (227). Formation of secondary and tertiary amine side-products can be hindered by the addition of acetic anhydride (228) or excess ammonia (229). In some cases secondary amines are the desired products. 

Primary, secondary, and tertiary amines react with sulfamic acid to form ammonium salts (28) ... 

The majority of U(V1) coordination chemistry has been explored with the trans-ddo s.o uranyl cation, UO " 2- The simplest complexes are ammonia adducts, of importance because of the ease of their synthesis and their versatihty as starting materials for other complexes. In addition to ammonia, many of the ligand types mentioned ia the iatroduction have been complexed with U(V1) and usually have coordination numbers of either 6 or 8. As a result of these coordination environments a majority of the complexes have an octahedral or hexagonal bipyramidal coordination environment. Examples iuclude U02X2L (X = hahde, OR, NO3, RCO2, L = NH3, primary, secondary, and tertiary amines, py n = 2-4), U02(N03)2L (L = en, diamiaobenzene n = 1, 2). The use of thiocyanates has lead to the isolation of typically 6 or 8 coordinate neutral and anionic species, ie, [U02(NCS)J j)/H20 (x = 2-5). 

High molecular weight primary, secondary, and tertiary amines can be employed as extractants for zirconium and hafnium in hydrochloric acid (49—51). With similar aqueous-phase conditions, the selectivity is in the order tertiary > secondary > primary amines. The addition of small amounts of nitric acid increases the separation of zirconium and hafnium but decreases the zirconium yield. Good extraction of zirconium and hafnium from ca 1 Af sulfuric acid has been effected with tertiary amines (52—54), with separation factors of 10 or more. A system of this type, using trioctylarnine in kerosene as the organic solvent, is used by Nippon Mining of Japan in the production of zirconium (55). 

Choline is not usually encountered as the free base but as a salt, most commonly, the chloride, [(CH2)3N(CH2CH20H)] C1 . As a quaternary ammonium hydroxide, choline reacts with hydrochloric acid to form the chloride and water, whereas primary, secondary, and tertiary amines combine with hydrochloric acid to form hydrochlorides. 

Because the heavy ethyleneamines are very complex materials, assays by titration in aqueous and nonaqueous media are often performed (151). The result is usually expressed as an amine number or amine value, a measure of the total basic nitrogen content of the product. Titrimetric procedures are also available to define primary, secondary, and tertiary amine content (152). 

Dissociation extraction is the process of using chemical reac tion to force a solute to transfer from one liquid phase to another. One example is the use of a sodium hydroxide solution to extract phenolics, acids, or mercaptans from a hydrocarbon stream. The opposite transfer can be forced by adding an acid to a sodium phenate stream to spring the phenolic back to a free phenol that can be extrac ted into an organic solvent. Similarly, primary, secondary, and tertiary amines can be protonated with a strong acid to transfer the amine into a water solution, for example, as an amine hydrochloride salt. Conversely, a strong base can be added to convert the amine salt back to free base, which can be extracted into a solvent. This procedure is quite common in pharmaceutical production. 

Primary, secondary and tertiary amines can serve as starting materials. The amine, e.g. 1, is first treated with excess methyl iodide, to generate the quaternary ammonium iodide 5. Subsequent treatment with silver oxide in water gives the corresponding ammonium hydroxide 2 ... 

The above equation adequately accounts for the action of ammonia, but it may function in other ways as well, for a variety of bases, such as tertiary amines, carbonates (46), and hydroxides 20,32), also suppress formation of coupled products. Greenfield (28) suggested that bases may function by suppressing the hydrogenolysis reaction leading to secondary and tertiary amines. 

Symmetrical secondary and tertiary amines are named by adding the prefix di- or tri- to the alkyl group. 

Unsymmetrically substituted secondary and tertiary amines are named as iV-substituted primary amines. The largest alkyl group is chosen as the parent name, and the other alkyl groups are N-substituents on the parent (jY because they re attached to nitrogen). 

We ve already studied the two most general reactions of amines—alkylation and acylation. As we saw earlier in this chapter, primary, secondary, and tertiary amines can be alkylated by reaction with a primary alkyl halide. Alkylations of primary and secondary amines are difficult to control and often give mixtures of products, but tertiary amines are cleanly alkylated to give quaternary ammonium salts. Primary and secondary (but not tertiary) amines can also be acylated by nucleophilic acyl substitution reaction with an acid chloride or an acid anhydride to yield an amide (Sections 21.4 and 21.5). Note that overacylation of the nitrogen does not occur because the amide product is much less nucleophilic and less reactive than the starting amine. 

Non-aqueous titrations have been used to quantify mixtures of primary, secondary and tertiary amines,5 for studying sulphonamides, mixtures of purines and for many other organic amino compounds and salts of organic acids. 

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