Chlorine amino acid hydrochlorides

The recent interest in applying chlorine-35/37 SSNMR spectroscopy to amino acid hydrochlorides stems from their biological importance, as they serve as simple models for chloride ion binding sites in ion channels. We have reported... 

Figure 13 Summary of the chlorine-35 isotropic chemical shifts for solid amino acid hydrochlorides. Reproduced from Ref. 182 by permission of the PCCP Owner Societies.

The above-mentioned optimal methods were also used in combination with experimental chlorine NMR data to refine the hydrogen-bonded proton positions in some amino acid hydrochlorides for which neutron diffraction data are unavailable. The combined experimental-theoretical procedure provided proton positions which resulted in back-calculated values of the chlorine quadrupolar coupling constant typically within 15% of experiment. The values of O were found to be less sensitive to the proton positions. 

D.L. Bryce, G.D. Sward, Chlorine-35/37 NMR spectroscopy of solid amino acid hydrochlorides refinement of hydrogen-bonded proton positions using experiment and theory, J. Phys. Chem. B 110 (2006) 26461-26470. 

R.P. Chapman, D.L. Bryce, A high-field C1 NMR and quantum chemical investigation of the chlorine quadrupolar and chemical shift tensors in amino acid hydrochlorides, Phys. Chem. Chem. Phys. 9 (2007) 6219-6230. 

The synthesis of 3-alkyl-substituted 1,2-thiazetidine 1,1-dioxides starts by transformation of the amino acids L-Val, L-Leu, L-Ile, and L-Phe into amino alcohols. These ate converted via the bromides to the corresponding thiols 161. Immediate oxidative chlorination affords either sulfonyl chloride hydrochlorides or sulfonic acids 162 which are transformed into the parent /3-sultams 163 <2004HCA90>. Similarly, L-cystine derivatives 164 have also been transformed into the parent /3-sultams 165 by oxidative chlorination followed by cyclization (Scheme 50) C1997LA1261, 2004HCA90>. 

A route to a-enaminocarboxylic acid esters based on N-chlorination/ dehydrochlorination of amino acid esters has been described by H. Poisel and U. Schmidt 312, 313). N-Chlorination of BOC-amino acid esters followed by dehydrochlorination with methoxide affords a-methoxy-a-BOC-amino acid esters (41), which, on treatment with HCl, undergo elimination of methanol and cleavage of the protective group in a single step. The free enamino esters (42) are liberated from their hydrochlorides by treatment with ammonia or triethylamine. NMR spectroscopic studies showed that (42a) and (42c) exist exclusively in the enamino tautomeric form, while (42b) contains about 40% imino tautomer. 

Chloroprocaine Chloroprocaine, the 2-diethylaminoethyl ester of 2-chloro-4-aminoben-zoic acid (2.1.5), is the ortho-chlorinated (in relation to the carbonyl group of the benzene ring) analog of procaine. Synthesis of this drag is accomplished by directly reacting the hydrochloride of the 4-amino-2-chlorbenzoic acid chloride (2.1.4) with hydrochloride of diethylaminoethanol. The hydrochloride of 4-amino-2-chlorbenzoic acid chloride needed for synthesis is synthesized by reacting 2-chloro -aminobenzoic acid with thionyl chloride [5],... 

Shaprio described a nonoxidative method for preparing 2-substituted 4-ox-azolecarboxylic acid esters 591 (Scheme 1.161). He prepared the key intermediate, dimethyl amino[(phenylthio)methyl]malonate 588, in three straightforward steps from diethyl aminomalonate hydrochloride. Acylation of 588 gave the A-acyl derivative 589 in excellent yield, which was sequentially chlorinated and cyclized in one pot to afford the 2,4,4,5-tetrasubstituted oxazoline 590. The author noted that anhydrous conditions were required to minimize sulfoxide formation. This was the only product isolated if the chlorination cyclization sequence was carried out in a hydroxylic solvent. 

Reaction of glycosylamines or aminosugars 1 with diethyl (ethoxymethyl-ene)malonate to give the corresponding enamine derivatives 2 was found [32-34] to be quite an efficient procedure for protecting amino moieties in carbohydrates, stable in both acidic and basic conditions (Scheme 1). Deprotection is carried out in moist dichloromethane with chlorine or bromine, to give hydrochloride or hydrobromide 3, usually crystalline. 

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