Amino acids hydrochlorides

Example 36 Four batches. A, B, C, and D, of an amino acid hydrochloride were investigated four different titration techniques were applied to every sample ... 

Jacobsen and co-workers also described the highly enantioselective hydrocyanation of ketimines with the urea analogue. After recrystallisation of the corresponding Strecker adduct, formylation and hydrolysis, the N-benzyl R-methylphenylglycine, was obtained. The R-amino acid hydrochloride is obtained in 93% overall yield with > 99.9% ee on a gram scale [149]. 

A precipitate of the amino acid hydrochloride which formed on cooling is dissolved during the reaction. 

The synthesis of jS-hydoxy-a-amino acids is important since these compounds are incorporated into the backbone of a wide range of antibiotics and cyclopeptides such as vancomycins. These highly functional compounds are also subject to dynamic kinetic resolution (DKR) processes, as the stereocenter already present in the substrate epimerizes under the reaction conditions and hence total conversions into single enantiomers are possible. These transformations can be iy -selective ° for N-protected derivatives as shown in Figure 1.27 when using a mthenium-BlNAP catalyzed system and anfi-selective when the jS-keto-a-amino acid hydrochloride salts are reduced by the iridium-MeOBlPHEP catalyst as shown in Figure 1.28. One drawback is that both these reductions use 100 atm hydrogen pressure. 

Strong carbonyl absorption at 1755-1730 cm1 for a-amino acid hydrochlorides, and at 1730-1700 cm1 for other amino acid hydrochlorides. 

Boc-18-crown-6-L-DOPA (4 66.4 g, 0.133 mol) was treated for 2h with 4M HQ in dioxane. After concentration to dryness under vacuo, the amino acid hydrochloride obtained (57.96 g, 0.133 mol) was dissolved in a H20/MeCN (1 9) mixture. DIPEA (69 mL) and Fmoc-OSu (49.80 g, 0.148 mol) were then added portionwise to the soln which was stirred mechanically for 3 h. The solvents were removed under reduced pressure and the residual oil was dissolved in CH2C12. The organic phase was washed with 1 M HC1 then water. After drying (MgS04), the solvent was removed and the residue was triturated with Et20 to give 5 as a white solid yield 95% mp 110-114°C TLC Rj 0.30 (silica gel, CHCl/MeOH/AcOH 70 15 15) [a]D25 -14.8 (c 1, DMF). 

In the amino acid hydrochloride salts, normal carbonyl absorption is observed for the —C02H group except that the band is displaced by about 20 cm-1 to... 

Mani, K.N. 2000. A process for simultaneous production of amino acid hydrochloride and caustic via electrodialytic water splitting. Eur. Pat. Appl, EP no. 1,016,651, July, 5th, 2000. 

Removal of the f-butyloxycarbonyl groups was obtained by treatment of 34a with a solution of trifluoroacetic acid in dichloromethane (1 1,0°C, 3 h). N-N-Hydroge-nolysis was achieved under H2 (75 psi, rt, 15 h) in the presence of a catalytic amount of Pt02 in ethanol to afford crystalline a-amino esters 36. Finally, the chiral auxiliary was cleaved and regenerated by nondestructive transesterification in the presence of Ti(OEt)4. The a-amino acid hydrochlorides (5)-37 were obtained by heating the crude amino acid ethyl esters in 6 N aqueous HC1 and after evaporation of the solution (Scheme 16). 

Applications of the method to w-amino acids were discussed and existing knowledge was summarized by Marik et al. [258]. Silylation was executed at 80°C for 1— 2 h or at 90°C for 0.5-1 h, with the use of BSA either alone or with the addition of triethylamine or acetonitrile. BSA alone was recommended as tris-TMS derivatives were produced in practically 100% yield. The presence of amine and solvent led to the formation of bisand tris-derivatives in various ratios, changing with time. However, these conclusions were valid only if the reaction was started with amino acid hydrochlorides. The presence of... 

Chloride ions are three- and four-coordinated. The neutron diffraction analyses of the amino acid hydrochlorides provided the data in Thble 11.1, and the more extensive data obtained from the X-ray analyses of hydrochlorides of nucleic acid constituents are given in Thble 11.2. The data indicate clearly that the chloride ion may be three- or four-coordinated. When three-coordinated, the bonds may be in planar or in pyramidal configuration, with no bimodal distribution. The ligands of four-coordinated chloride ions are only very approximately in tetrahedral con-... 

Table 11.1. - N(H)2H Cl hydrogen-bond lengths to chloride ions in the amino acid hydrochlorides from neutron diffraction data...

Fig. 14.4 for L-lysine HCl 2H20 [LYSCLH11]. A is chloride in only three amino acid hydrochloride salts, see L-phenylalanine HCl [PHALNC01] in Fig. 14.5. 

The solution is evaporated to dryness under reduced pressure on a water bath. In order to remove as much hydrochloric acid as possible, the temperature of the bath is raised to 100° toward the end of the distillation. The residue of amino acid hydrochloride and inorganic salts is suspended in 500 cc. of absolute ethyl alcohol. The suspension is boiled on a steam bath for a short time, then cooled to room temperature and filtered on a Buchner funnel. The residue of inorganic salts is washed with 500 cc. of absolute ethyl alcohol. To the combined filtrates is added 400 cc. of ethyl ether (u. s. p. quality) in order to precipitate inorganic material. After several hours the mixture is filtered, and the residue is washed with a 5 2 mixture of absolute ethyl alcohol and ether. The filtrate is transferred to a 5-1. round-bottomed flask, about 200 cc. of water is added, and the liquids are removed by distillation under reduced pressure. The nearly dry residue is dissolved in 2 1. of water, and the solution is treated with an excess of freshly prepared lead hydroxide (Note 5). The suspension is diluted with water to a volume of about 3.5 1. and is then concentrated under reduced pressure, at as low a temperature as possible, to a volume of about 2 1. The suspension is then filtered with suction (Note 6), and the residue of lead salts is washed thoroughly with water. The cloudy filtrate, which still contains some free ammonia, is concentrated by distillation under reduced pressure to a volume of about 300-400 cc. The mixture is filtered, the filtrate is saturated with hydrogen sulfide gas, and the precipitate of lead sulfide is removed by filtration with suction (Note 6). The solution is now concentrated by distillation under reduced pressure on a water bath, and 1 1. of 95 per cent ethyl alcohol is added to the nearly dry residue of the amino acid. The suspension is boiled under a reflux condenser until nearly all the amino acid is dissolved, and the mixture is then allowed to cool to room temperature. The amino acid, which separates in the form of fine needles, is collected on a Buchner funnel and washed with a little 95 per cent ethyl alcohol. A second crop of... 

Sodium metal (166 mmol) is dissolved in 100 mL ethanol under an inert atmosphere in a round-bottom flask fitted with a water condenser. Diethyl acetam-ido malonate (138 mmol) is then added, followed by 193 mmol the 1-bromo-alkane of choice (e.g., 1-bromodecane will provide C12 Laa). The solution is refluxed overnight under an inert atmosphere. Upon cooling, the mixture is poured onto 600 mL crushed ice and stirred. The aminodiester product precipitates and is collected on a Buchner funnel and air-dried. The crude product is then refluxed overnight in a 200-mL solution of HChDMF (9 1). Upon cooling, the product precipitates and is collected on a Buchner funnel, washed with ice water, and air-dried to afford the a-amino acid hydrochloride typically in >90% crude yield. 

Amino acid methyl esters are fairly simple to prepare. The classical method uses a suspension of amino acid hydrochloride in MeOH and gaseous HCl as catalyst b° l di-carboxylic acids yield the dimethyl esters.Hydrolytic and alcoholytic cleavage of side-chain amide groups of glutamine and asparagine as well as peptide bond cleavage prevents the use of this method for the esterification of peptide fragments. 

Lead oxide is used in an early procedure for the conversion of an amino acid hydrochloride into the free amine. A solution of alanine hydrochloride in water is... 

Methyl esters. 2,2,-Dimethoxypropane has been used for the preparation of methyl esters of amino acid hydrochlorides. The reagent serves as solvent and as a source of the methoxyl group, and it removes water. The amino acid is suspended in 2,2,-dimethoxypropane, a small volume of coned, hydrochloric acid is added, and... 

Similarly, the diethyl 2-(3-oxocyclopentyl)- and 2-(4-oxocyclohexyl)ethylphosphonates have been subjected to the standard Bucherer-Berg reaction conditions [KCN, (NH4)2CO, NH4CI in EtOH-HjO at 60°C] to give spirohydantoins, which are isolated as a mixture of cis- and trans-isomers. Hydrolysis of hydantoins needs heating at 150°C in a sealed tube with concentrated HCl to provide the amino acid hydrochlorides. ... 

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