The first type of such shorthand to become widely used by organic chemists is the name reaction. At first, name reactions were used sparingly and almost always in reference to reactions that were already widely used and well known. In this way, a name reaction was more widely viewed as a tribute to the discoverer of a highly useful reaction. For example, within the dozen years after its first appearance in the literature, Victor Gri- gnard’s synthesis of alcohols by the reaction between an alkyl- or arylmagnesium halide and a carbonyl compound had become so widely used that almost all chemists knew what was meant by the term, “Grignard’s synthesis.” Within the same time period, the Grignard reaction had so completely displaced the previous methods—also name reac- tions using organozinc reagents—that it was the reaction of first choice for the synthesis of alcohols.
This general principle—that a reaction on which the discoverer’s name was conferred should be both widely known and widely used—stood for much of the 20th century, and
1. Review: Pettit, R. Pure Appl. Chem. 1968, 17, 253.
2 Katz T.J.; Acton N. J. Am. Chem. Soc. 1973, 95, 2738.
Chapter three
Organic Shorthand: Acronyms and Name Reactions
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conferring a name on a reaction was thus sparingly done. Toward the end of that century, however, the proliferation of variations on a theme and the need for using a specific varia- tion of a particular reaction meant that the use of name reactions and named reagents began to be used more as a shorthand to describe the explicit version of the base reaction being used rather than as a tribute to the discoverer of the generic reaction. This trend still continues.
Unfortunately, this very proliferation of named reactions and reagents has made a chapter like this increasingly necessary in modern organic synthesis—few people can keep the full set of named reactions and reagents clear in their minds (and that includes this author!).3 Over the course of this book, we will discuss many name reactions. Some of the oldest named reactions—all from before World War I—are gathered (in alphabetical order) in Table 3.1. The list is not exhaustive, and it has expanded by a large amount in the century that followed.
When you examine the list, you will find many reactions that you have already learned in your introductory course in organic chemistry; it is worthwhile taking some time to review them. Unless you have been asked for a superhuman effort, you will not have studied all the reactions in Table 3.1, so do not be discouraged if you find reactions that you are not familiar with. When you examine Table 3.1, you will find two rather obvious omissions from the list—Markovnikov’s rule4 for addition and Zaitsev’s rule5 for elimination. Likewise, substituent effects on regiochemistry in aromatic substitution are not in the table.
3. There are several books and monographs devoted to name reactions that have appeared in recent years: (a) Kürti, L.; Czakó, B. Strategic Applications of Named Reactions in Organic Synthesis (Academic Press: New York, 2005). (b) Li, J.J. Name Reactions. A Collection of Detailed Mechanisms and Synthetic Applications, 4th ed.
(Springer-Verlag: Berlin, 2009). (c) Mundy, B.P.; Ellerd, M.G.; Favaloro, F.G. Name Reactions and Reagents in Organic Synthesis, 2nd ed. (Wiley-Interscience: New York, 2005).
4. (a) Markownikoff, W. Ann. Chem. Pharm. 1870, 133, 228. (b) Markovnikov, V. Compt. Rend. 1875, 82, 668, 728, 776.
5. Saytzeff, A. Justus Liebigs Ann. Chem. 1875, 179, 296.
Reaction Name Reaction Year Ref.
Baeyer-Villiger oxidation R R'
O R'CO3H R
O O
R' 1899 6
Beckmann rearrangement N
R'
R OH
NH R' O PCl5 R
1886 7
Blaise reaction CO2R
Br R
R 1) Zn, R'CN R'
CO2R R R
2) HCl/H2O O 1901 8
Borodin-Hunsdiecker
reaction R OAg R Br
O Br2 1861 9
Table 3.1 Long-standing Name Reactions
6. Baeyer, A.; Villiger, V. Ber. dtsch. chem. Ges. 1899, 32, 3625; 1900, 33, 858.
7. Beckmann, E. Ber. dtsch. chem. Ges. 1886, 19, 988.
8. Blaise, E.E. Compt. rend. 1901, 132, 478.
9. Borodine, A. Ann. Chem. Pharm. 1861, 119, 121; Z. Chem. 1861, 4, 5; 1869, 12, 342; Ann. Chem. Pharm. 1869, 121, 119.
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Reaction Name Reaction Year Ref.
Bouveault-Blanc reduction R CO2R' R'OHNa R OH 1903 10
Claisen condensation R CO2Et
O CO2Et R R
NaOEt
1881 11
Claisen rearrangement O ∆ OH 1912 12
Clemmensen reduction Zn(Hg), HCl, ∆
R R
H O H
R
R 1913 13
Darzens condensation CO2R' X
R R"2C=O base
O R"
R" R
CO2R' 1904 14 Demyanov rearrangement NH2 HONO
OH + CH2OH 1903 15
Dieckmann condensation COCO22EtEt NaOEt
O CO2Et
1894 16
Diels-Alder reaction + 1929 17
Étard oxidation Ph Me CrO2Cl2 Ph CHO 1880 18
Friedel-Crafts acylation
Cl X
R Ar
X R AlCl3
Ar-H 1877 19
Fries rearrangement
OCOR OH
COR AlCl3
1908 20
Gattermann-Koch reaction Ar H HCN, HClAlCl Ar CHO
3 1897 21
Glaser coupling R H CuCl, O2 R R 1869 22
10. Bouvealt, L.; Blanc, G. Compt. Rend. 1903, 136, 1676; Bull. Soc. Chim. France [3], 1904, 31, 666.
11. Claisen, L.; Claparède, A. Ber. dtsch. chem. Ges. 1881, 14, 2460.
12. Claisen, L. Ber. dtsch. chem. Ges. 1912, 45, 3157.
13. Clemmensen, E. Ber. dtsch. chjem Ges. 1913, 46, 1837; 1914, 47, 51, 681.
14. Darzens, G. Compt. rend. 1904, 139, 1214; 1905, 141, 766; 1906, 142, 214.
15. (a) Demyanov, N.Ya. Zh. Russ. Fiz.-Khim. O-va. 1903, 35, 26; 1904, 36, 186. (b) Demjanov, N. Chem. Zentr.
1903, I, 828; 1904, I, 1214; Ber. dtsch. chem. Ges. 1907, 40, 4393, 4961; 1908, 41, 43.
16. Dieckmann, W. Ber. dtsch. chem. Ges. 1894, 27, 102, 965; 1900, 33, 595, 2670; Ann. Chem. Pharm. 1901, 317, 51, 93.
17. Diels, O.; Alder K. Justus Liegigs Ann. Chem. 1929, 460, 98.
18. Étard, A.L. Compt. rend. 1880, 90, 534; Ann. Chim. Phys. [5] 1881, 22, 218.
19. Friedel, C.; Crafts, J.M. Compt. rend. 1877, 84, 1392, 1450.
20. (a) Fries, , K.; Fink, G. Ber. dtsch. chem. Ges. 1908, 41, 4271. (b) Fries, K.; Pfaffendorf, W. Ber. dtsch. chem.
Ges. 1910, 43, 212.
21. Gattermann, L. Ber. dtsch. chem. Ges. 1898, 31, 1149; Ann. Chem. Pharm. 1907, 357, 313.
22. Glaser, C. Ber. dtsch. chem. Ges. 1869, 2, 422; Ann. Chem. Pharm. 1870, 154, 159.
(continues)
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23. (a) Barbier, P. Compt. rend. 1899, 128, 110. (b) Grignard, V. Compt. rend. 1900, 130, 1322; 1901, 133, 336, 558;
1902, 134, 849; Chem. Zentr. 1901, II, 622; Ann. Chim. Phys. 1901, 24 [vii], 433. (c) Grignard, V.; Tissier, L. Compt.
rend. 1901, 133, 835; 1902, 134, 107.
24. (a) Hantzsch, A. Ann. Chem. Pharm. 1882, 215, 1, 72; Ber. dtsch. chem. Ges. 1885, 18, 1744; 1886, 19, 289.
25. (a) Hell, C. Ber. dtsch. chem. Ges. 1881, 14, 891. (b) Volhard, J. Ann. Chem. Pharm. 1887, 242, 141.
(c) Zelinskii, N. Ber. dtsch. Chem. Ges. 1887, 20, 2026.
26. Hofmann, A.W. Ber. dtsch. chem. Ges. 1881, 14, 2725.
27. (a) Curtius, T. J. prakt. Chem. [2] 1894, 50, 275. (b) Lossen, W. Ann. Chem. Pharm. 1874, 161, 347; 1875, 175, 271, 313.
28. (a) Kizhner, N.; Zavadovskii, A. Zh. Russ. Fiz.-Khim. O-va. 1911, 43, 1132. (b) Kizhner, N. Zh. Russ. Fiz.- Khim. O-va. 1912, 434, 1132165, 849; 1913, 45, 949, 957, 987; 1915, 47, 1102.
29. (a) Kolbe, H. Ann. Chem. Pharm. 1860, 113, 125. (b) Schmitt, R. J. prakt. Chem. [2] 1885, 31, 397.
30. Michael, A. J. prakt. Chem. [2] 1887, 35, 349.
31. Perkin, W.H. J. Chem. Soc. 1868, 21, 53, 181; J. Chem. Soc. 1877, 31, 388.
32. Prileschajew, N. Ber. dtsch. chem. Ges. 1909, 42, 4811.
Reaction Name Reaction Year Ref.
Grignard reaction R X 1) Mg, Et2O
2) R'2C=O OH R R'
R' 1900 23
Hantzsch pyridine synthesis R
CO2Et O
2 R' CHO
NH3 N
H R'
CO2Et EtO2C
R R
1882 24
Hell-Volhard-Zelinskii reaction
R OH
O Br2, P R Br OH
O
1881 25
Hofmann rearrangement R KOH, Br2 R NH2
NH2
O
1881 26
Hofmann, Curtius, Lossen rearrangements
O NH
R X N C O
R 1874–1894 27
Kishner cyclopropane synthesis
R1 R2
O R3
1) N2H4
2)KOH, Pt-kaolin, ∆ R3 R2
R1 1911 28
Kolbe carbonation
ONa CO2, Na2CO3
∆, pressure
OH
CO2Na 1860 29
Michael addition Ar CO2R NaOEt EtO2C Ar
EtO2C
CH2(CO2Et)2 CO2R
1887 30
Perkin condensation Ph CHO Ac2O Ph CO2H
AcONa, ∆ 1868 31
Prilezhaev reaction
R
R R
R RCO2OH O
R
R R
R 1909 32
(Table 3.1 continued)
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Reaction Name Reaction Year Ref.
Reformatskii reaction Br CO
2R R
R Zn, R'2CO HO
CO2R R' R'
R R
1887 33
Reimer-Tiemann reaction
OH OH
CHO CHCl3
KOH 1876 34
Stobbe condensation Ar CHO EtO2C
CO2Et NaOEt, EtOH, ∆
CO2Et CO2H
Ar 1893 35
Strecker amino acid
synthesis R CHO R
1) HCN, NH3
2) HCl, H2O, ∆
CO2H NH2
1850 36
Tollens oxidation R CHO Ag(NH3)2OH
R CO2H 1882 37
Ullmann Coupling Ar Br R INa Ar R 1881 38
Wagner-Meerwein
rearrangement Cl + Cl
HCl 1899 39
Wolff-Kishner reduction N2H4, KOH, ∆
R R
H O H
R
R 1911 40
Wurtz coupling R X Na R R 1855 41