Hydrochloride salts, of amines

N-Methyl-IV-trimethylsilyltrifluoroacetamide (MSTFA) is the most volatile TMS-amide available it is more volatile than BSTFA or BSA. Its by-product, A/-methyltrifluoroacetamide, has an even lower retention time in glc than MSTFA. This is of considerable value in glc determinations where the reagent or by-products obscure the derivative on the chromatogram. Silylation of steroids (qv) shows MSTFA to be significantly stronger in donor strength than BSTFA or BSA. A/-Methyl-A/-trimethylsilyltrifluoroacetamide silylates hydrochloride salts of amines directly. 

Amine Acyl chloride Amide Hydrochloride salt of amine... 

The hydrochloride salt of this amine was prepared by dissolving the amine in ether and adding ethereal hydrogen chloride to the ether solution. The solid hydrochloride salt which precipitated was racrystallized from an ethanol-ether mixture and was found to melt at 154°-155°C. 

These reactions are often conducted in water, or in acetone-water mixtures for higher molecular weight amines.Magnesium sulfate is frequently used as an additive in these reactions to control solution pH. 1,3,5,7-Tetranitroadamantane (71) has been obtained via the permanganate oxidation of the hydrochloride salt of 1,3,5,7-tetraaminoadamantane (70) (Table 1.7). The 45 % yield for this reaction reflects a relative yield of 82 % for the oxidation of each of the four amino groups. 

If nitration under acidic conditions could only be used for the nitration of the weakest of amine bases its use for the synthesis of secondary nitramines would be severely limited. An important discovery by Wright and co-workers " found that the nitrations of the more basic amines are strongly catalyzed by chloride ion. This is explained by the fact that chloride ion, in the form of anhydrous zinc chloride, the hydrochloride salt of the amine, or dissolved gaseous hydrogen chloride, is a source of electropositive chlorine under the oxidizing conditions of nitration and this can react with the free amine to form an intermediate chloramine. The corresponding chloramines are readily nitrated with the loss of electropositive chlorine and the formation of the secondary nitramine in a catalytic cycle (Equations 5.2, 5.3 and 5.4). The mechanism of this reaction is proposed to involve chlorine acetate as the source of electropositive chlorine but other species may play a role. The success of the reaction appears to be due to the chloramines being weaker bases than the parent amines. 

Wright illustrated the effectiveness of chloride-catalyzed nitration for a number of amines of different basicity. Wright showed that weakly basic amines like iminodiacetonitrile and its dimethyl and tetramethyl derivatives are all nitrated in high yield with nitric acid-acetic anhydride mixtures in the absence of chloride ion. In contrast, the slightly more basic 3,3 -iminodipropionitrile is not appreciably nitrated with acetic anhydride-nitric acid, but the inclusion of a catalytic amount of the hydrochloride salt of the amine base generates the corresponding nitramine in 71 % yield. ... 

Wright found it more suitable to use the nitrate salts of the more basic amines, like in the case of morpholine, which ignites at ambient temperature in the presence of nitric acid-acetic anhydride mixtures. Morpholine nitrate is not nitrated with acetic anhydride-nitric acid in the absence of chloride ion at room temperature, but the addition of 4 mole % of zinc chloride generates a 65 % yield of A-nitromorpholine, and this yield rises to 93 % if the hydrochloride salt of morpholine is directly nitrated. While morpholine nitrate is unaffected by treatment with acetic anhydride-nitric acid at room temperature, the same reaction in the presence of ammonium nitrate at 65 °C is reported to yield A-nitromorpholine in 48 % yield. ... 

Many cyclic, bicyclic and caged polyamines are synthesized via condensation reactions and these are usually isolated as their salts. The free bases are usually difficult to isolate and readily decompose in aqueous or acid solution. Since hydrochloric acid is frequently employed in these condensations the hydrochloride salt of the amine is usually used directly for the A-nitration. 

Scheme 10.8 outlines the application of rhodium-catalyzed allyhc amination to the preparation of (il)-homophenylalanine (J )-38, a component of numerous biologically active agents [36]. The enantiospecific rhodium-catalyzed allylic amination of (l )-35 with the lithium anion of N-benzyl-2-nitrobenzenesulfonamide furmshed aUylamine (R)-36 in 87% yield (2° 1° = 55 1 >99% cee) [37]. The N-2-nitrobenzenesulfonamide was employed to facilitate its removal under mild reaction conditions. Hence, oxidative cleavage of the alkene (R)-36 followed by deprotection furnished the amino ester R)-37 [37, 38]. Hydrogenation of the hydrochloride salt of (l )-37 followed by acid-catalyzed hydrolysis of the ester afforded (i )-homophenylalanine (R)-3S in 97% overall yield. 

At 180°C the hydrochloride salt of 145 is transformed into 146 with excess 145, whereas with other amines 4-amino derivatives are formed. Metha-nolic hydrogen sulfide yields 12 (R = Ph) from 147. ... 

The pyrazolo[3,4-( ][l,2,3,4]tetrazine derivative 49 has been reported to be formed by treatment of the hydrochloride salt of the amine 48 with sodium nitrite in aqueous ethanol at room temperature. Only a single example was described. Compound 49 was obtained as red crystals (m.p. >300°C). The product is presumed to form from the diazonium cation 50 which cyclizes via the hydrazone tautomer 51 (Scheme 2) <1998MI11>. 

Disadvantages of the silver-promoted method for Amdt-Eistert homologation are the large excess of nucleophile required and also the requirement for the use of the free amine during peptide formation procedures. 13 Activation of the diazo ketone by UV light has been shown to be suitable for this type of procedure and good yields are obtained using only 1.2 equivalents of a hydrochloride salt of an amino ester in the presence of triethylamine (Scheme 5). 14 ... 

This synthetic procedure, using the hydrochloride salt of the amine and sodium cyanoborohydride in methanol, seems to be quite general for ketone compounds related to 3,4-methylenedioxyphenylacetone. Not only were most of the MD-group of compounds discussed here made in this manner, but the use of phenylacetone (phenyl-2-propanone, P-2-P) itself appears to be equally effective. The reaction of butylamine hydrochloride in methanol, with phenyl-2-propanone and sodium cyanoborohydride at pH of 6, after distillation at 70-75 °C at 0.3 mm/ Hg, producedN-butylamphetamine hydrochloride (23.4 g from 16.3 g P-2-P). And, in the same manner with ethylamine hydrochloride there was produced N-ethyl-amphetamine (22.4 g from 22.1 g P-2-P) and with methy lamine hydrochloride there was produced N-methylamphetamine hydrochloride (24.6 g from 26.8 g P-2-P). The reaction with simple ammonia (as ammonium acetate) gives consistently poor yields in these reactions. 

When amino acid ester prodrugs of acetaminophen were prepared (Kovach et al., 1975 Pitman, 1976), the hydrobromide salt of the glycine ester showed enhanced solubility in water, but the hydrochloride salt of th -aspartic acid ester exhibited a solubility lower than that of the parent compound. The enhanced solubility resulted from the formation of a salt, while the parent drug is a weakly acidic phenol and behaves as essentially a neutral molecule in solution. The reduced solubility in the case of th0-aspartic acid ester resulted from ionization of the terminal carboxylic acid, which, with the protonated amine, gives a zwitterionic compound. The zwitterion also behaved as a molecule with an overall neutral character, as is commonly observed with zwitterion behavior in aqueous media, but its larger size resulted in a further reduced solubility. 

Sertraline is an antidepressant that is sold as a single enantiomer and prepared commercially through a resolution of a racemate. The starting material for the resolution step is the hydrochloride salt of racemic sertraline (13.22) (Scheme 13.3). The hydrochloride salts are first neutralized through the addition of NaOH to form the racemic free amine (13.23). The amine is then reacted with 1.0 equivalents of d-(— )-mandelic acid (13.24) in ethanol to form diastereomeric salts. The solution of the salts in ethanol is allowed to stand at room temperature, and a solid consisting of predominantly diastereomer 13.25 precipitates. Filtration of the solid followed by recrystallization from ethanol affords essentially... 

Hydrochloride salts of scheduled 2.B.10, 2.B.11 and 2.B.12 chemicals should be named as the free amines with the addition of hydrochloride. 

If present, these modify the functional group(s), e.g., in 3-amino-2-chloro-2-butenoic acid, ethyl ester, hydrochloride. Modifications are used for anhydrides, esters, and salts of acids, oxides, sulfides, and selenides of ring systems containing P and As, hydrazones, and oximes of carbonyl compounds, salts of amines, etc. 

Acid salts of amines (and other basic parents) are indexed at the molecular formulae of the amines. Thus, methanamine hydrochloride appears under CHjN (methanamine) and not under CHgClN. 

These products may also be prepared from the reaction of COCi, with the hydrochloride salt of the secondary amine [1451]. In some cases, ureas are formed immediately, for example, in the reactions of piperidine [1652] or 2,2 -bipiperidine [668] with phosgene [1652] ... 

Simple tertiary amines can be grafted to a carbon skeleton, either by exchange reactions or by Mannich reactions. The hydrochloride salt of the camptothecin derivative (a) (Figure 38.15) is soluble in water at concentrations up to 1 mg/mL the comparable value for camptothecin itself is 0.0025 mg/mL. Similar results were obtained in solubilizing the benzodiazepine (b) and the quinazolinone (c). The adenosine Ai antagonist KW-3902 (d) was solubilized in an original manner by converting it to an amidinic and cyclized bioisostere (e). ... 

For other tertiary amino substrates the situation is unclear (e.g., compare the conflicting results in the reactions of 2-dimethylamino-l -phenylpropanone hydrochloride), bui there is definite evidence that using the hydrochloride salts of these amines degrades the syn selectivity60,61. 

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