1
35
Synlett
P. B. Cranwell et al.
Letter
In conclusion a simple, safe, and cheap method for the
conversion of ketones and aldehydes into their correspond-
ing methylene has been disclosed. Significant safety ad-
vances have been made, reducing exposure to the volatile,
suspect carcinogenic and teratogenic hydrazine. The inter-
ception of the classical Wolff–Kishner intermediate means
that this protocol can be easily adapted to previously de-
scribed examples that have utilised hydrazine.
(16) Cook, A. H.; Linstead, R. P. J. Chem. Soc. 1934, 946.
(17) Quast, H.; Ivanova, S.; Peters, E.-M.; Peters, K. Eur. J. Org. Chem.
2000, 507.
(
(
(
18) Szmant, H. H.; Harmuth, C. M. J. Am. Chem. Soc. 1964, 86, 2909.
19) Zengin, G.; Huffman, J. W. Turk. J. Chem. 2006, 30, 139.
20) (a) Balandin, A. A.; Vaskevich, D. N. J. Gen. Chem. (USSR) 1936, 6,
1878. (b) Todd, D. J. Am. Chem. Soc. 1949, 71, 1356.
(21) (a) Seibert, W. Chem. Ber. 1947, 80, 494. (b) Seibert, W. Chem.
Ber. 1948, 81, 266.
(22) (a) Szmant, H. H. Angew. Chem., Int. Ed. Engl. 1968, 7, 120.
(
1
b) Szmant, H. H.; Birke, A.; Lau, M. P. J. Am. Chem. Soc. 1977, 99,
863. (c) Szmant, H. H.; Alciaturi, C. E. J. Solution Chem. 1978, 7,
Acknowledgment
2
69.
Use of the Chemical Analysis Facility (CAF) at the University of Read-
ing is gratefully acknowledged.
(
(
23) Szmant, H. H.; Alciaturi, C. E. J. Org. Chem. 1977, 42, 1081.
24) Yamabe, S.; Zeng, G.; Guan, W.; Sakaki, S. Beilstein J. Org. Chem.
2
014, 10, 259.
Supporting Information
(
(
25) Taber, D. F.; Stachel, S. J. Tetrahedron Lett. 1992, 33, 903.
26) (a) Garland, K.; Gan, W.; Depatie-Sicard, C.; Beauchemin, A. M.
Org. Lett. 2013, 15, 4074. (b) Lavergne, K.; Bongers, A.; Betit, L.;
Beauchemin, A. M. Org. Lett. 2015, 17, 3612.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1560805.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
(27) Wiznycia, A. V.; Desper, J.; Levy, C. J. Chem. Commun. 2005,
4693.
References and Notes
(
28) General Procedure 1
(
(
(
(
1) All authors contributed an equal amount of work.
2) Kishner, N. J. Russ. Phys. Chem. Soc. 1911, 43, 582.
3) Wolff, L. J. Liebigs Ann. Chem. 1912, 394, 86.
4) (a) Wicha, J. Reduction of Carbonic or Carboxylic Acids, Alde-
hydes, Ketones or Derivatives, In Science of Synthesis: Houben-
Weyl Methods of Molecular Transformation; Vol. 48; Hiemstra,
H., Ed.; Thieme: Stuttgart, 2009, 97. (b) Hutchins, R. O.;
Hutchins, M. K. Reduction of C=X to CH2 by Wolff–Kishner and
Other Hydrazone Methods, In Comprehensive Organic Synthesis;
Vol. 8; Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991,
To the aldehyde or ketone (1.0 g) in EtOH (5–10 mL) was added
methyl hydrazinocarboxylate (1.3 equiv) followed by a few
drops of AcOH. The reaction was heated at reflux overnight and
then cooled to r.t. The product was either purified by recrystal-
lization by dropwise addition of H O, cooling upon ice, and col-
2
lection of the product by Büchner filtration, or the solvent was
removed in vacuo and the crude product purified by flash
column chromatography to give the carbomethoxyhydrazones.
General Procedure 2
KOH (4 equiv)* was dissolved in triethylene glycol (5 mL) and
the solution was heated to 100 °C, forming an orange solution.
The carbomethoxyhydrazone (0.5 g) was added in one portion,
and the reaction was further heated at 140 °C for 4 h after
3
27. (c) Reusch, W. In Reduction; Augustine, R. L., Ed.; Marcel
Dekker: New York, 1968, 171. (d) Huang-Minlon, Sci. Sinica
961, 10, 711. (e) Buu-Hoï, N. P.; Hoán, N.; Xuong, N. D. Recl.
1
Trav. Chim. Pays-Bas 1952, 71, 285. (f) Todd, D. The Wolff–
Kishner Reduction, In Organic Reactions; Vol. 4; Adams, E., Ed.;
John-Wiley and Sons: London, 1948, 378. (g) Bashore, C. G.;
Samardjiev, I. J.; Bordner, J.; Coe, J. W. J. Am. Chem. Soc. 2003,
which time the reaction was cooled, diluted with H O, and
2
extracted with Et O. The organic phase was dried (MgSO ), fil-
2
4
tered, and the solvent removed in vacuo. The crude product was
purified by flash column chromatography to provide the desired
products as pale yellow oils. *Add one more equivalent KOH per
acidic group present.
125, 3268.
(
(
5) Staudinger, H.; Kupfer, O. Ber. Dtsch. Chem. Ges. 1911, 44, 2194.
6) (a) Huang-Minlon J. Am. Chem. Soc. 1946, 68, 2487. (b) Huang-
Minlon J. Am. Chem. Soc. 1949, 71, 3301.
Representative Data for Methyl (E)-2-[1-(4-Bromophe-
nyl)ethylidene]hydrazine-1-carboxylate (Table 1, entry 2)
(
(
(
7) Soffer, M. D.; Soffer, M. B.; Sherk, K. W. J. Am. Chem. Soc. 1945,
1
H NMR (400 MHz, CDCl ): δ = 7.98 (1 H, br s, NH), 7.63 (2 H, d,
3
6
7, 1435.
8) Herr, C. H.; Whitmore, F. C.; Schiessler, R. W. J. Am. Chem. Soc.
945, 67, 2061.
J = 8.8 Hz, CH ), 7.49 (2 H, d, J = 8.8 Hz, CH ), 3.88 (3 H, s,
Ar Ar
OCH ), 2.19 (3 H, s, CH ). 13C NMR (100 MHz, CDCl ): δ = 147.5
3
3
3
1
(C=N), 136.8 (C Br), 131.6 (C H), 127.9 (C H), 123.6 (C ), 53.3
Ar Ar Ar Ar
9) Kuethe, J. T.; Childers, K. G.; Peng, Z.; Journet, M.; Humphrey, G.
(OCH ), 12.7 (CH ). IR (neat): ν
= 3196, 2945, 1730, 1702,
3
3
max
R.; Vickery, T.; Bachert, D.; Lam, T. T. Org. Process Res. Dev. 2009,
1539, 1484 cm–1
.
HRMS (ESI ): m/z was calcd for
+
13, 576.
C10H12O N 79Br: 271.0077 [M + H]
+
; found: 271.0077. Mp 152–
2
2
(
(
10) Nagata, W.; Itazaki, H. Chem. Ind. (London) 1964, 1194.
11) Cram, D. J.; Sahyun, M. R. V.; Knox, G. R. J. Am. Chem. Soc. 1962,
155 °C (EtOH).
Representative Data for 1-Bromo-4-ethylbenzene (Table 1,
entry 2)
84, 1734.
(
(
12) Szmant, H. H.; Roman, M. N. J. Am. Chem. Soc. 1966, 88, 4034.
13) Grundon, M. F.; Henbest, H. B.; Scott, M. D. J. Chem. Soc. 1963,
1
H NMR (400 MHz, CDCl ): δ = 7.83 (2 H, d, J = 8.4 Hz, CHAr),
3
7.06 (2 H, d, J = 8.4 Hz, CH ), 2.59 (2 H, q, J = 7.6 Hz, CH CH ),
Ar
2
3
1855.
1.21 (3 H, t, J = 7.6 Hz, CH CH ). 13C NMR (100 MHz, CDCl ):
2
3
3
(
(
14) Furrow, M. E.; Myers, A. G. J. Am. Chem. Soc. 2004, 126, 5436.
15) (a) Barton, D. H. R.; Ives, D. A. J.; Thomas, B. R. J. Chem. Soc. 1955,
δ = 143.2 (C ), 131.3 (C H), 129.6 (C H), 119.3 (C Br), 28.3
Ar
Ar
Ar
Ar
(CH CH ), 15.5 (CH CH ). IR (neat): ν
= 3022, 2963, 2928,
2
3
2
3
max
2056. (b) Barton, D. H. R.; O’Brien, R. E.; Sternhell, S. J. Chem. Soc.
2871, 1485 cm–1
.
1962, 470. (c) Barton, D. H. R.; Bashiardes, G.; Fourrey, J.-L. Tet-
rahedron Lett. 1983, 24, 1605. (d) Barton, D. H. R.; Bashiardes, G.;
Fourrey, J.-L. Tetrahedron 1988, 44, 147.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 131–135