Amines, aliphatic

Amines are derivatives of ammonia in which one or more of the hydrogen atoms has been replaced by an alkyl group. They are divided into primary RNH2), secondary (R2NH) or tertiary amines (RjN) according to the number of hydrogen atoms that have been replaced. The introduction of a fourth alkyl group leads to the tetra-alkyl or quaternary ammonium salts (R N X ). 

A number of methods involve the rearrangement of carboxylic acid derivatives via nitrenes. The best known of these is the Hofmann degradation of amides. This involves treating an amide with bromine and alkali. The A-bromo compound undergoes an a-elimination in the presence 

Amines can displace a halide or a derivative of an alcohol, such as the methanesulfonate or toluene-4-sulfonate, with the eventual formation of a quaternary ammonium salt. Reaction with ammonia may lead to mixtures, since the initial alkylation increases the basicity of the nitrogen, and hence the primary amine reacts more rapidly than ammonia. Further reaction, although enhanced by the increase in basicity, may be impeded by steric hindrance arising from the additional alkyl groups. 

The hydrogen of a primary or secondary amine is sufficiently acidic to form sodium or lithium amides. Thus treatment of diethylamine with butyl-lithium affords the strong base lithium diethylamide (Et N Li ). 

The acetyl, benzoyl and toluene-4-sulfonyl derivatives of amines are often crystalline, and have been used to characterize the amine. The addition of an amine to an isocyanate may lead to a substituted urea and these have also been used to characterize the amines. 

Aliphatic amines. Colthup [21] has ako indicated correlations for aliphatic amines with absorptions in the 1220—1020 cm range. This correlation has been confirmed and extended by Stewart [19] by measurements on numbers of primary and secondary amines. He proposed much more limited sub-divkions depending on the degree of substitution at the a-carbon atom. Secondary amines with a primary a-carbon atom absorb at 1139 + 7 cm , and this rises to 1181 T 10 when the a-carbon atom is a secondary one. 

Primary amines show three ranges, 1079 + 11 cm for primary a-carbons, 1040+ 3 cm for secondary a-carbons and 1030 + 8 cm for the tertiary cases. These bands are reported to be strong in the infra-red, but some caution is needed in their use for diagnosis. However the bands always appear clearly and are well recognisable in the Raman spectra which provides a valuable confirmation. 

Tertiary amines are difficult to identify in the infra-red. The most characteristic bands are the antisymmetric and symmetric C—N stretching modes and these can best be identified in the Raman spectra where the former occurs in the range 1070—1050 cm and the latter near 830 cm .  

In unsaturated tertiary amines it k possible to differentiate between a 3- and 07-unsaturation by observing the frequency changes which occur in the 1600—1700 cm region on salt formation [87]. 

1 Aliphatic Amines The molecular ion peak of an aliphatic monoamine is an odd number, but it is usually quite weak and, in long-chain or highly branched amines, undetectable. The base peak fre- 

A peak at m/z 30 is good though not conclusive evidence for a straight-chain primary amine. Further decomposition of the first-formed ion from a secondary or tertiary amine leads to a peak at m/z 30, 44, 58, 72,. ... This is a process similar to that described for aliphatic alcohols and ethers above and, similarly, is enhanced by branching at one of the a-carbon atoms  

Cleavage of amino acid esters occurs at both C— C bonds (a, b below) next to the nitrogen atom, loss of the carbalkoxy group being preferred (a). The aliphatic amine fragment decomposes further to give a peak at m/z 30. 

Sulfamation is not possible with tertiary amines which react with chlorosulfonic acid to form the corresponding amine-sulfur trioxide complex (see p 175). 

The three classes of amines also react differently with organic sulfonyl chlorides this is exploited in the Hinsberg separation of primary, secondary and tertiary amines.  

Many organic sulfamic acids are sweet, consequently a wide range of alkyl, alicyclic and aromatic derivatives has been synthesized in the search for new nonnutritive sweeteners. One of the best synthetic routes to sulfamic acids involved treatment of the appropriate primary amine 140 (three equivalents) with chlorosulfonic acid (one equivalent) in an inert organic solvent such as chloroform, followed by neutralization with sodium hydroxide to yield the corresponding sodium sulfamate 141 and the amine for recovery and recycling (Equation 57).  

Sodium iV-cyclohexyl sulfamate (cycliunate, 141 R = cyclohexyl) was introduced as a non-nutritive artificial sweetener in 1939. It is 30 times sweeter than sucrose, but was banned in the USA and Canada in 1970 because rats fed with large doses developed bladder cancer, although it is permitted in many other countries. Cyclohexylammonium sulfamate, an intermediate in the manufacture of non-nutritive sweeteners, may be prepared by reaction of cyclohexylamine (two to three equivalents) with chlorosulfonic acid in trichloroethene at 60-75 C the presence of the excess amine avoids an acidic medium and side reactions. A-Cyclohexylsulfamic acid has been obtained by treatment of cyclohexylamine with a mixture of sulfur trioxide and chlorosulfonic acid in trichloroethene at 60 Cyclamate can also be manufactured by heating cyclohexylamine with sulfamic acid in xylene at 132-139 Benson and Spillane discussed the 

In A-substituted sulfamic acids, exceptional sweetness was discovered to be generally limited to those members containing a cyclohexyl ring which may be substituted, a free hydrogen atom attached to the nitrogen atom and almost any salt-forming group (X) as shown 142.  

Imines are one group of compounds that are similar to amines. Imines contain an ammonia molecule in which two hydrogen atoms are displaced by bivalent hydrocarbon radicals (R=NH). Nitriles are another group of compounds that are similar to amines. In nitriles all the hydrogen atoms in ammonia are displaced by a trivalent hydrocarbon radical (ROH). 

Methylamines are colorless liquids that are volatile at normal atmospheric conditions. They have threshold odor limits of less than 10 ppm, and at low concentrations they have a fishy smell. At high concentrations they smell like ammonia. The physical properties are given in Table 14.1 and Table 14.2. 

Various modifications of the reaction of an alcohol with ammonia provide the most common commercial routes to alkylamines. Some others routes that are used to make certain individual amines include aldehyde/amine additions, nitrile reduction, the Ritter reaction, amination of isobutylene, and hydrogenation of anilines. Capacities of many plants depend on the product mix of mono/di/tri products as well as the variety of amines (ethyl, propyl and butyl). One must know the product mix that the capacity is based upon and the actual scheduled output of produces) to determine what amounts can actually be manufactured. Capacities are often in excess of anticipated demand to satisfy seasonal demands for pesticide uses116. 

In Alcohol Amination, methanol and excess ammonia react at 350°C to 500°C and 15 to 30 bar in the presence of aluminum oxide, silicate or phosphate catalysts according to the following reactions46  

The reactions shown in Eqs. (14.1) through (14.3) are known as the Alkylation reactions. They are exothermic and highly irreversible, except for Eq. (14.3). The reactions in Eqs. (14.4) through (14.6) are known as Disproportionation reactions. They are reversible and are endothermic. The alkylation reactions dictate the rate of consumption of methanol and are somewhat faster than the disproportionation rates that govern the selectivity of the three amines. 

Teichert et al. [45] were the first to carry out TLC of amines. The hydrochlorides were dissolved in 70% alcohol and applied in 1 to 10 [xg amounts. The hi /-values and experimental conditions for the separation are summarised in Table 94. As can be seen from the table, only a partial improvement in separation is achieved by buffering silica gel G layers with a mixture of 0.2M primary potassium phosphate and 0.2 M secondary sodium phosphate (1 -h 1) or with 0.15M sodium acetate solution. 

Amine Silica gel G-Iaycr Buffered silica gel G layer Cellulose powder layer VE 

Geasshof [8] quotes similar thin-layer chromatographic behaviour on magnesium silicate (Firm 153), using chloroform-methanol (50 + 50) or n-propanol-water-chloroform (66 + 22 -f 11) for amines or the analogous aminoalcohols, respectively. On the other hand, the TLC-separation of aminoalcohols on neutral alumina (Firm 153) and of amines on sihca gel (Firm 153) and on neutral alumina, using the same solvents, has proved unsatisfactory. 

Primary and secondary amines are identified with certainty by preparing the 3,5-dinitrobenzamides (DNBs) and separating them on normal silica gel G layers with chloroform-ethanol (99 +1). The hi /-values found for the DNBs of the following amines are [14, 45] methylamine 14, dimethylamine 47, ethylamine 68, n-propylamine 38, i-butylamine 42, i-amylamine 50. 

50 mg of the amine hydrochloride or 25 mg of free amine, dissolved in 5 ml water in a separating funnel, are treated with 15 ml ether, 0.25 ml pyridine and 250 mg 3,5-dinitrobenzoyl chloride, dissolved in 1 ml benzene. Potassium carbonate (5.5 g) is added with cooling and continuous stirring. After 20 min, the aqueous layer is discarded and the ether phase shaken with two 5 ml portions of 1% sulphuric acid and finally with water. The ethereal solution is then dried over sodium sulphate, filtered and evaporated to dryness. If necessary, the DNB product is crystallised from 50% ethanol. For TLC, 5—25 (xg amounts are applied as a 1% solution in ether or chloroform. 

Depending on the number of amine groups in the molecule, the amine can be a mono-, di-, tri-, or polyamine. Aliphatic amines can also be classified by their molecular structure as linear, branched, aliphatic, or containing aromatic groups. However, the most valuable method of classification is by functionality. 

The functionality of an amine is determined by the number of reactive hydrogens present on the molecule. The amines typically have greater than three reactive sites per molecule that facilitate the formation of the crosslinked epoxy structure. The difference between primary, secondary, and tertiary amines is reflected by the number of hydrogens that are bound to each nitrogen atom  

The primary and secondary amines are discussed in this section. The secondary amines are derived from the reaction product of primary amines and epoxies. They have rates of reactivity and crosslinking characteristics that are different from those of primary amines. The secondary amines are generally more reactive toward the epoxy group than are the primary amines, because they are stronger bases. They do not always react first, however, due to steric hindrance. If they do react, they form tertiary amines. Tertiary amines are primarily used as catalysts for homopolymerization of epoxy resins and as accelerators with other curing agents. 

The chemical structures of important amines for curing epoxy resins in adhesive systems are identified in Fig. 5.1. Diethylenetriamine (DETA), triethylenetetramine (TETA), ra-aminoethylpiperazine (AEP), diethylaminopropylamine (DEAPA), ra-phenylenediamine (MPDA), and diaminodiphenyl sulfone (DDS) are the most commonly used members of this class. They are all primary amines. They give room or elevated temperature cure at near stoichiometric ratios. Ethylenediamine is too reactive to be used in most practical adhesive formulations. Polyoxypropyleneamines (amine-terminated polypropylene glycols) impart superior flexibility and adhesion. 

An early study of cyclic amine acidities by Hall [189] using Hammett constants produced good linear plots for the pK s, while a study of aliphatic amines using Taft constants also produced linear plots, with separate lines for the primary, secondary, and tertiary amines [190]. Ballinger and Long [191] found a linear correlation between the pK s of a number of alcohols and Taft o values, with p = 1.42 for the dissociation reaction, errin [182] later summarized acidity results using Hammett constants for benzene derivatives in the expressions 

When branching at the a-carbon is absent, an M - 1 peak is usually visible. This is the same type of 

Cleavage of amino acid esters occurs at both C—C bonds (dashed lines below) next to the nitrogen 

Hermanson et al. [71] used an aluminium column (276cm x 4mm) packed with 80-100 mesh Chromosorb W supporting 8.9% of amine 220 at 95°C with nitrogen as carrier gas and flame ionisation detection. A rectilinear response was obtained between peak area and amoimt of propylamine, dipropylamine, and propanol between 0.2 and 2.0pg. 

Gas flame ionisation chromatography has been used to determine dimethylamine [72,73], dimethylformamide [72], propylamine [73] and diispropylamine [71] in river water and industrial effluents. To separate 

Temperoture 240°C WCOTgloss CP Sil 7 tailor mode for pesticides Corriergos Argon-methone 95-5 

Source Reproduced by permission from SpringerYerlag, Heidelbei [70] 

Cj-Ci mono-, di- and trialkylamines, Onuska [73] adjusted the pH of the sample to between 5 and 8. A IpL aliquot of the filtrate was injected on to a stainless steel column (185cm x 2mm id) packed with 28% of Pennwalt 223 and 4% of potassium hydroxide on Gas-Chrom R (80-100 mesh) and maintained at 134°C. A dual-flame iorusation detector was used and the carrier gas was helium (flow rate 52.2ml min ). The detector response was rectilinear between lOng and at least lOOpg of dimethylamine, and the reproducibility was good. The column could be regenerated by increasing the coluirm temperature to greater than 180°C. 

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Colourless liquid with a characteristic ammo-niacal smell m.p. 9 C, b.p. 106°C. Miscible with water. It is present in pepper as the alkaloid piperine from which it can be obtained by healing with alkali. It can also be prepared by the reduction of pyridine, either electrolytically or by other means. Piperidine is a strong base, behaving like the aliphatic amines. 

Jeanmaire D L and Van Duyne R P 1977 Part I heterocyclic, aromatic and aliphatic amines adsorbed on the anodized silver electrode J. Electroanal. Chem. 84 1-20... 

Aromatic primary amines differ markedly from aliphatic amines in their reaction with nitrous acid. Thus a cold aqueous solution of mono thylamine hydrochloride reacts with nitrous acid to give mainly the corresponding primary alcohol ... 

A) PRIMARY AROMATIC AMINES. RNH. Aniline, o-, m-, and p-toluidine (and other nuclear-substitiited anilines) 1- and 2-naphthylamines. (For note on Aliphatic Amines, cf. p. 375 )... 

R NHa + C.HjNCO = RNH CO NHC,Hj Traces of water will contaminate the product with diphenylurea (p. 336) if the solution is boiled hence the need for anhydrous conditions. i-Naphthylisocyanate reacts more slowly with water, and the i-naphthyl-urea derivative can often be obtained using a cold aqueous solution of an aliphatic amine it is particularly necessary in such cases to purify the product by recrystallisation from, or extraction with, boiling petroleum, leaving behind any insoluble di i-naphthylurea. Note that the amine must also be free from alcohols (p. 335) and phenols (p. 337). 

Note. PRIMARY ALIPHATIC AMINES. The lower amines are gases or low-boiling liquids (b.ps. CHjNH, 7 CiHjNH, 17 CH,(CH2,>,NH 49 (CHg)jCHNHa, 34 ) but may be encountered in aqueous or alcoholic solution, or as their crystalline salts. They are best identified as their benzoyl, or toluene-/>-sulphonyl derivatives (c/. (C) above), and as their picrates when these are not too soluble. This applies also to benzylamine, CjHsCHjNH, b.p. 185 also to ethylenediamine, usually encountered as the hydrate, NHj (CHj)j NH2,HjO, b.p. 116 , for which a moderate excess of the reagent should be used to obtain the di-acyl derivative. (M.ps., pp. 55 55 )... 

The more important reactions of aliphatic amines, which will assist in their detection, are given below. 

Crysialline Derivatives of Primary and Secondary Aliphatic Amines... 

The melting points of the derivatives of some primary and secondary aliphatic amines are collected in Table 111,123. 

Tertiary aliphatic amines are discussed under Aromatic Tertiary Amines ill Section IV, 100. 

They are readily hydrolysed by boiling dilute hydrochloric acid and the original amine can be recovered by neutralisation with alkali and steam distillation. Primary aliphatic amines liberate nitrogen with nitrous acid whilst tertiary amines are unaffected. 

The modified procedure involves refluxing the N-substituted phthaUmide in alcohol with an equivalent quantity of hydrazine hydrate, followed by removal of the alcohol and heating the residue with hydrochloric acid on a steam bath the phthalyl hydtazide produced is filtered off, leaving the amine hydrochloride in solution. The Gabriel synthesis has been employed in the preparation of a wide variety of amino compounds, including aliphatic amines and amino acids it provides an unequivocal synthesis of a pure primary amine. 

Primary aromatic amines differ from primary aliphatic amines in their reaction with nitrous acid. Whereas the latter yield the corresponding alcohols (RNHj — ROH) without formation of intermediate products see Section 111,123, test (i), primary aromatic amines 3neld diazonium salts. Thus aniline gives phcnyldiazonium chloride (sometimes termed benzene-diazonium chloride) CjHbNj- +C1 the exact mode of formation is not known, but a possible route is through the phenjdnitrosoammonium ion tlius ... 

Those reactions which are common to both aliphatic and aromatic amines and have been described under Aliphatic Amines (Section 111,123) will not be repeated in this Section except where differences in experimental technique occur. 

Picrates. Experimental details will be found under Aliphatic Amines, Section 111,123, 3. 

Experimental details are given for the cyanoethylatlon of primary alcohols and of secondary aliphatic amines ... 

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