COMMUNICATIONS TO THE EDITOR
June, 1948
Sa9i
objectionable vigor during the ultimate decomposition with water or dilute acid. The yield is estimated by the usual acidimetric titration. RESEARCH LABORATORIES OF THEWM. S. MERRELLCOMPANY CINCINNATI, OHIO RECEIWD MARCH8, 1948
powder is vigorously stirred under 1 liter of, refluxing anhydrous ether. One mole of the slkoxybenzyl halide dissolved in 1 1. of ether is added over a two to five hour interval. The resulting Grignard reagent is then filtered through glass cotton to remove the finely divided magnesium powder, which if not removed usually reacts with
COMMUNICATIONS T O T H E EDITOR CHEMICAL REACTIONS IN MOVING BOUNDARY SYSTEMS OF WEAK ELECTROLYTES Sir :
From equation (2) we see that the mobility, u , calculated from the boundary velocity in this case is the “constituent” mobility. The acetate ion mobility, u & ~ -
In moving boundary systems containing partially neutralized weak acids or bases there exists the possibility of chemical reactions at the moving boundary which cause the mobility calculated from the boundary velocity and the conductivity calculated from the constituent mobility obtained of the leading solution to be lower than the ionic in experiments 2 and 3 by using equation (3) are and - 17.55 X in agreement mobility.’ This is illustrated by experiments 2 - 17.62 X and 3 in which the indicator electrolyte is a salt with the average value, - 17.53 X lod, obtained of weak acid (cacodylic acid) having a higher in experiments 1 and 4. However, in systems containing weak elecpK than the leading weak electrolyte (acetic acid). The following reaction goes to completion trolytes the constituent mobility is not always TABLE Iu
-
Moving Boundary Systemb
Y
(1) NaOAc(0.05) 4 (2) NaOAc(0.05), HOAc(0.05) (3) NaOAc(O.05), HOAc(0.01) (4) NaOAc(O.05) 4 (5) NaOAc(0.05),HOAc(O.05) OAc, acetate; Cac, cacodylate; T , trichloroacetate. 67,1109 (1945), are used.
+
Dii
+ C;oao)
P
&o-GLoKY
LI
x
l(yl
(OOC.)
NaCac : :NaCac -17.47 NaCac, HCac: :NaCac 8.81 XaCac, HCac: :NaCac 5.85 XaT : :NaT -17.59 NaT,HOAc : :NaT -16.54 The conventions recommended by Longsworth, THISJOURNAL,
to the right a t the moving boundary so that none of the acetic acid remains behind that boundary. CacHOAc HCac + OAc- KW = 25 (1) The concentration of the sodium acetate is 0.05 N (at 0’) in all experiments, and it has been shown that the concentration and pH of the indicator electrolyte (a solution) is unimportant over a wide range. The moving boundary equation2 cannot be applied to acetate ion in the presence of acetic acid, but a term may be added for the acetic acid as follows so that the moving boundary equation for acetate constituent becomes
aA0-Vfly(CJ,,-
u B
1000/F (2)s
(1) Dr. Harry Svensson, Institutes of Physical and Biological Chemistry, U p d a , Sweden, has independently recognized this fact in work initiated in September, 1946 (Acto Chrm. Scond., in press), personal communication. (2) Weber, Sifrrcngsbrr. Akod. Wissensch. Berlin, 936 (1897); Svensson, Ark. Kmn. Min. Grol., 1711, No. 14 (1943); Longsworth, Tars JOURNAL,W, 1109 (194s). (8) The m b o l s have the mcsninsa uod by Lorrsoworth (Con,k taken unegative),
-
obtained as illustrated by experiment 5. Whether or not a chemical reaction takes place depends upon the pK and relative mobility of the indicator ion. In this experiment the mobility calculated is slightly lower than the ionic mobility because the acetate ion does not disappear in the Br boundary, owing to the slight dissociation of the acetic acid left behind the moving boundary. Since proteins and buffers used in electrophoresis are weak electrolytes, reactions such as the above occur and must be considered in the quantitative interpretation of electrophoretic patterns. DEPARTMENT OF CHEMISTRY UNIVERSITY OF WISCONSIN ROBERTA. ALBERTY J. C. NICHOL MADISON, WISCONSIN RECEIVED MAY25, 1948
SYNTHESIS OF DLTHREONWE
Sir: The structure a-amino-8-hydroxy-n-butyric acid contains two dissimilar asymmetric carbon atoms and hence exists as four optical isomers and
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Vol. 70
two racemic modifications. Attempts to syn- 40.42; H, 7.32; N, 11.82. This product was thesize one of these racemic modifications, the found 1 0 0 ~ opure by microbial assay and better essential amino acid DL-threonine, have invariably than 99% pure by solubility analysis, given poor results, though some of the syntheses Additional work now in progress indicates that have produced the diastereoisomeric DL-allo- the “oxazoline inversion” described may be a genthreonine in good yields. Efforts to convert DL- eral method for the interconversion in high yield allothreonine into DL-threonine have met with of diastereoisomeric a,P-amino alcohols. little success. KARLPFISTER,3rd. It has now been found that esters of N-acyl-DL- RESEARCH LABORATORIES C. A. ROBINSON A. C. SHABICA allothreonine are converted into DL-threonine in MERCK& Co., INC. MAXTISHLER high yield b y transformation into the correspond- RAHWAY,N. J. RECEIVED MAY12, 1948 ing oxazolines followed by hydrolysis of the latter with mineral acid. N-Benzoyl-m-allothreonine was treated with THE TOTAL SYNTHESIS OF SPARTEINE diazometham and the methyl ester (m. p. 110- sir: 111’. Anal. Calcd. for C12H1604N: C, 60.76; We wish to report a convenient total syntheH, 6.36. Found: C, 60.86; H, 5.99.) on reaction with excess thionyl chloride a t room temperature sis of dl-sparteine (I). The Lupin alkaloid 1gave 2-phenyl-5-methyl-4-carbomethoxyoxazoline hydrochloride, m. p. 118-119’, in quantitative yield. Anal. Calcd. for C12H1303N”Cl: C, 56.36; H, 5.52. Found: C, 56.50; H, 5.71. Hydrolysis 1 with dilute hydrochloric acid followed by isolation and recrystallization gave pure D-threonine in sparteine was f i s t isolated in 1851 and the correct 70% yield. Anal. Calcd. for C4H903N : C, 40.33; structure (I) was confirmed by Clemo and Raper’ H, 7.62; N, 11.76. Found: C, 40.35; H, 7.70; in 1933. 1-Sparteine is used in medicine chiefly N, 11-46. By the same sequence of steps N-ben- as a cardiac stimulant and a diuretic.2 dzoyl-m-threonine was converted into pure DL-allo- Sparteine a d the naturally occurring alkaloid pachycarpine*have been shown to be identical.‘ threonine in 77% over-all yield. Our synthesis of dl-sparteine proceeds in two A practical synthesis of DL-threonine from acetoacetic ester has been developed by the use of steps from ethyl 2-pyridylacetate. The first step this inversion. Ethyl a-acetamidoacetoacetate, was the preparation of l-carbethoxy-4-keto-3obtained in SSyoyield from acetoacetic ester via (2‘-pyridyl)-pyridocolineby condensation of ethyl reductive aoetylation of ethyl a-phenylazoaceto- orthoformate with ethyl 2-pyridylacetate in the acetate, was, hydrogenated in aqueous solution presence of acetic anhydride according to the with Adams catalyst to give on concentration a method of Clemo, Morgan and Raper.s The mixture of diastereoisomeric ethyl a-acetamido-8- second step was that of reductive cyclization, hydroxy-n-butyrates containing 80-85% N- which was reported first from this Laboratory6 acetyl-m-allothreonine ethyl ester. A purified for the synthesis of pyrrolizidines. 1-Carbethoxysample of this product melted a t 76-77’. Anal. 4-keto-3-(2’-pyridyl)-pyridocolinein dioxane was Calcd. for CBH,sO$rT : C, 50.78; H, 7.99. Found: hydrogenated over copper chromite a t 250’ and C, 50.54; H, 8.04. f i e crude hydrogenation 350 atm. in one and one-half hours. The prodproduct was ,treated with thionyl chloride, and the uct was separated into three fractions: b. p. 90solution was refluxed with water to decompose the 120’, 120-126’, 140-148’ (1.25 mm.). The intermediate oxazoline. An isolated sample of second and largest fraction gave a monopicrate this 2,5-dirnethyl-4-carbethoxyoxazolinehydro- (m. p. 136-137’; Anal. Calcd. for &lHzsNa07: chloride melted a t 105-106’. Anal. Calcd. for C, 54.42; H, 6.31; N, 15.11. Found: C, 54.55; CeHlaOsN.HC1: C, 46.27; H, 6.79; N, 6.75; N. H, 6.49; N, 15.18) and a dipicrate (m. p. 208’; E., 207.7. Found: C, 46.11; H, 6.87; N, 6.97; Anal. Calcd. for Cz7HsaNsOla: C, 46.82; H, N. E., 202.2. The aqueous solution was concen- 4.66; N, 16.18. Found: C, 46.76; H, 4.88; txgted dry and the amino acid hydrochloride taken N, 16.28). The analyses and melting points of up in isopropanol and precipitated with aniline. the derivatives are consistent with the assignment The crude product (89% yield from ethyl a- of the dl-sparteine structure to the synthetic free acetamidoacetoacetate) was a mixture of DL- base. Clemo and Leitch7reported a monopicrate threonine and ~~-allothreonine containing 83% (1) Clemo and Raper, J . Chcm. Soc., 644 (1933). (2) Wood and Owl. “United States Dispensatory,” J. B. Lippinof the former (microbial assay). Company. Philadelphia, Pa., twenty-third edition, 1943, p. Pure DL-threonine was obtained by separation cott 1013; “The Mer& Index,” Merck and Company, Rahway, N. J.. of the sodium salt from anhydrous alcohol, re- fifth edition. 1940, P. 524. (3) Orechov, Rabinowitch and Konovalova,B e . , 66, 621 (1933). conversion into the free acid and recrystallization (4) Galinovsky and Stern, ibid.. 99, 132 (1944). by precipitation from aqueous solution with alco(5) Clemo, Mormn and Raper, J . Chcm. Soc.. 1025 (1936). hol. The over-all yield of DL-threonine from (6) Leonard, Hruda and Long, THISJOURNAL, 6S, 690 (1947). acetoacetic ester was 57%. Anal. Found: C , (7) Clemo and Ltitch, J . Chrm. Soc., 1811 (1928).
