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Hell-Volhard-Zelinsky Reaction
Hell-Volhard-Zelinsky Reaction
Carl Magnus von Hell ( 1 8 4 9 - 1 9 2 6 ) was born in Stuttgart. Germany. He studied at Stuttgart under Fehling and at Munich under Erlenmeyer. After serving in the W a r of 1 870, during which he became very ill, von Hell returned to Stuttgart as an assistant to Fehling, whom he succeeded in 1883. In 1889, von Hell synthesized the paraffin hydrocarbon, C o H , which was the highest alkane known at that time. He is probably best known for his procedure for the bromination of acids in the presence of phosphorus. 6
*
*
1 2 2
*
Jacob Volhard ( 1 8 3 4 - 1 9 0 9 ) was born in Darmstadt, Germany. He received his doctor's degree in 1855 at Giessen, where he studied under Liebig and then under Will. He studied under Bunsen at Heidelberg for one year then received an assistantship at Munich to work with Liebig. From 1860 to 1861 Volhard served as an assistant to Hofmann in London. After spending a short time in Kolbe's laboratory in Marburg, he returned to Munich, where he became an associate professor. When von Baeyer succeeded Liebig, Volhard became director of the inorganic and analytical departments. During this period he worked on his well-known volumetric determinations. Volhard synthesized sarcosine ( 1 8 6 2 ) , guanidine, and creatine. With Erdmann ( 1 8 8 5 ) he published a synthesis of thiophene and derivatives from succinic acids. The need for a-bromo acids in this work led to the bromination procedure, which was an improvement over von Hell's method. Volhard was also interested in the synthesis of diphenylacetic acid esters. *
*
*
Nikolai D. Zelinsky ( 1 8 6 1 - 1 9 5 3 ) was born in Tyraspol, Russia. He studied at O d e s s a , at Leipzig, and at Gottingen, where he was
129
HELL-VOLHARD-ZELINSKY
REACTION
a student of Victor Meyer. He received his Ph.D. degree in 1889 at Odessa and became an assistant professor. In 1893, Zelinsky was appointed professor at the University of Moscow, where he became head of the department of organic chemistry. Zelinsky was a member of the U.S.S.R. Academy of Sciences. He was awarded the title of Hero of Socialist Labor in 1945, and in 1951 he celebrated his ninetieth birthday and received the Order of Lenin. During his long and fruitful career, Zelinsky published about 500 papers. Many of these contributions deal with the study of catalytic hydrogenations, dehalogenations, terpene chemistry, and synthetic rubber.
The preparation of a-chloro or a-bromo acids by the treatment of aliphatic carboxylic acids with chlorine or bromine usually in the presence of a small amount of the corresponding phosphorus trihalide is known as the Hell-Volhard-Zelinsky reaction. ' The formation of the acyl halide probably precedes halogenation, since it is known that halogens react more rapidly with acyl halides than with the acids themselves. The steps in the reaction may be formulated as follows: 1 2
3RCH COOH + PX 2
RCH COX + X 2
> 3RCH COX + H P 0
3
2
3
3
> RCHXCOX + HX
2
RCHXCOX + RCH COOH
• RCHXCOOH + RCH COX
2
2
The original Hell-Volhard procedure which involves the use of bromine and phosphorus probably proceeds also via the acyl bromide. An example of the bromination with phosphorus trichloride is the preparation of a-bromoisocaproic acid. 3
(CH ) CHCH CH COOH 3
2
2
2
—(CH ) CHCH CHBrCOOH PCI»
3
2
2
(66%)
Attempts to brominate /J-bromopropionic acid by the Hell-VolhardZelinsky method gave only /J-bromopropionyl bromide. An excellent procedure for the preparation of mono a-bromo derivatives of dicarboxylic acids has been described by Schwenk and Papa. The method involves treating the half-ester of dicarboxylic acids with thionyl chloride and then bromine. The bromo acid chloride thus obtained is treated with ethanol to give the bromo diester which can be purified by distillation. 4
5
130
HELL-VOLHARD-ZELINSKY REACTION SOCh
ROOC(CH ) CH COOH 2
n
2
ROOC(CH )„CHBrCOCl 2
Bra
• R'OH
•
ROOC(CH )„CH COCl 2
•
2
ROOC(CH ) CHBrCOOR' 2
n
E t h y l a-bromoadipate was obtained in 90% yield b y this m e t h o d . T h e p r o c e d u r e is also very satisfactory w i t h monocarboxylic acids a n d has given practically quantitative yields of ethyl a-bromocyclohexylacetate a n d ethyl a-bromophenylacetate. References
1. C. Hell, Ber. deut. Chem. Ges. 14, 891 (1881); J. Volhard, Ann. Chem. Liebigs 242, 141 (1887); N. Zelinsky, Ber. deut. Chem. Ges. 20, 2026 (1887). 2. H. B. Watson, Chem. Revs. 7,180 (1930). 3. C. S. Marvel, in "Organic Syntheses" (N. L. Drake, ed.), Vol. 21, p. 74. Wiley, New York, 1941. 4. E. H. Charlesworth and H. J. Anderson, Can. J. Research 28B, 1 (1950). 5. E. Schwenk and D. Papa, /. Am. Chem. Soc. 70, 3626 (1948).
131
Carl Magnus von Hell ( 1 8 4 9 - 1 9 2 6 ) was born in Stuttgart. Germany. He studied at Stuttgart under Fehling and at Munich under Erlenmeyer. After serving in the W a r of 1 870, during which he became very ill, von Hell returned to Stuttgart as an assistant to Fehling, whom he succeeded in 1883. In 1889, von Hell synthesized the paraffin hydrocarbon, C o H , which was the highest alkane known at that time. He is probably best known for his procedure for the bromination of acids in the presence of phosphorus. 6
*
*
1 2 2
*
Jacob Volhard ( 1 8 3 4 - 1 9 0 9 ) was born in Darmstadt, Germany. He received his doctor's degree in 1855 at Giessen, where he studied under Liebig and then under Will. He studied under Bunsen at Heidelberg for one year then received an assistantship at Munich to work with Liebig. From 1860 to 1861 Volhard served as an assistant to Hofmann in London. After spending a short time in Kolbe's laboratory in Marburg, he returned to Munich, where he became an associate professor. When von Baeyer succeeded Liebig, Volhard became director of the inorganic and analytical departments. During this period he worked on his well-known volumetric determinations. Volhard synthesized sarcosine ( 1 8 6 2 ) , guanidine, and creatine. With Erdmann ( 1 8 8 5 ) he published a synthesis of thiophene and derivatives from succinic acids. The need for a-bromo acids in this work led to the bromination procedure, which was an improvement over von Hell's method. Volhard was also interested in the synthesis of diphenylacetic acid esters. *
*
*
Nikolai D. Zelinsky ( 1 8 6 1 - 1 9 5 3 ) was born in Tyraspol, Russia. He studied at O d e s s a , at Leipzig, and at Gottingen, where he was
129
HELL-VOLHARD-ZELINSKY
REACTION
a student of Victor Meyer. He received his Ph.D. degree in 1889 at Odessa and became an assistant professor. In 1893, Zelinsky was appointed professor at the University of Moscow, where he became head of the department of organic chemistry. Zelinsky was a member of the U.S.S.R. Academy of Sciences. He was awarded the title of Hero of Socialist Labor in 1945, and in 1951 he celebrated his ninetieth birthday and received the Order of Lenin. During his long and fruitful career, Zelinsky published about 500 papers. Many of these contributions deal with the study of catalytic hydrogenations, dehalogenations, terpene chemistry, and synthetic rubber.
The preparation of a-chloro or a-bromo acids by the treatment of aliphatic carboxylic acids with chlorine or bromine usually in the presence of a small amount of the corresponding phosphorus trihalide is known as the Hell-Volhard-Zelinsky reaction. ' The formation of the acyl halide probably precedes halogenation, since it is known that halogens react more rapidly with acyl halides than with the acids themselves. The steps in the reaction may be formulated as follows: 1 2
3RCH COOH + PX 2
RCH COX + X 2
> 3RCH COX + H P 0
3
2
3
3
> RCHXCOX + HX
2
RCHXCOX + RCH COOH
• RCHXCOOH + RCH COX
2
2
The original Hell-Volhard procedure which involves the use of bromine and phosphorus probably proceeds also via the acyl bromide. An example of the bromination with phosphorus trichloride is the preparation of a-bromoisocaproic acid. 3
(CH ) CHCH CH COOH 3
2
2
2
—(CH ) CHCH CHBrCOOH PCI»
3
2
2
(66%)
Attempts to brominate /J-bromopropionic acid by the Hell-VolhardZelinsky method gave only /J-bromopropionyl bromide. An excellent procedure for the preparation of mono a-bromo derivatives of dicarboxylic acids has been described by Schwenk and Papa. The method involves treating the half-ester of dicarboxylic acids with thionyl chloride and then bromine. The bromo acid chloride thus obtained is treated with ethanol to give the bromo diester which can be purified by distillation. 4
5
130
HELL-VOLHARD-ZELINSKY REACTION SOCh
ROOC(CH ) CH COOH 2
n
2
ROOC(CH )„CHBrCOCl 2
Bra
• R'OH
•
ROOC(CH )„CH COCl 2
•
2
ROOC(CH ) CHBrCOOR' 2
n
E t h y l a-bromoadipate was obtained in 90% yield b y this m e t h o d . T h e p r o c e d u r e is also very satisfactory w i t h monocarboxylic acids a n d has given practically quantitative yields of ethyl a-bromocyclohexylacetate a n d ethyl a-bromophenylacetate. References
1. C. Hell, Ber. deut. Chem. Ges. 14, 891 (1881); J. Volhard, Ann. Chem. Liebigs 242, 141 (1887); N. Zelinsky, Ber. deut. Chem. Ges. 20, 2026 (1887). 2. H. B. Watson, Chem. Revs. 7,180 (1930). 3. C. S. Marvel, in "Organic Syntheses" (N. L. Drake, ed.), Vol. 21, p. 74. Wiley, New York, 1941. 4. E. H. Charlesworth and H. J. Anderson, Can. J. Research 28B, 1 (1950). 5. E. Schwenk and D. Papa, /. Am. Chem. Soc. 70, 3626 (1948).
131