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Synthesis of 1 n-Dicarbonyl Derivates Using Carbanions from 1 3-Dithianes.

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(instead of COz) at -7OOC the ethyl cdrboxylates (3) are
obtained [yields: (3u) 60
(3b) 78 7 3 which can be saponified (CH3OH/H*O/KOH) to the dithianecarboxylic acids.
2,2-Diisopropyl- 1,3-ditliinne by seqirentinl alkylntion of
To a solution containing 30 mmoles of the anion ( 4 ) , R = H ,
in tetrahydrofuran at -5 "C were added 5.60 g (33 mmoles)
of isopropyl iodide, and the mixture was maintained at
0 ° C for 14 h under nitrogen. The resulting solution of
2-isopropyl-l,3-dithianewas treated at -30 "C with 35
mmoles of n-butyl-lithium i n hexane and after 1.5 h 5.85 g
(35 mmoles) of isopropyl iodide were added. After a reaction period of 70 h at 0 ° C under nitrogen the reaction
mixture was poured into three times its volume of water,
acidified to pH 5-6 and extracted with five portions (30 ml
each) of pentane. After washing successively with 3
aqueous sodium bisulfite, 5 76 aqueous KOH, and water the
extract was dried (K2C03) and concentrated to give 5.82 g
(95 YL) of a nearly colorless oil which contained 15
2-isopropyl- 1,3-dithane and 85 %, of 2,2-diisopropyl-l,3-dithiane ( N M R analysis). Fractionation through a small (5 cm)
column gave 4.30 g (70 %) of pure 2,2-diisopropyl-l,3-di= 1.5392.
thiane (5), R==R=i-C3H7,b.p. 95'C,'0.5 mm,
Received: October 5th, 1965
[ Z 75/901 IEl
German version: Angew. Chem. 77, 1134 (1965)
[ l a ] J . F. Arens et a/., Rec. Trav. chim. Pays-Bas 78, 663 (1959);
81, 1009 (1962). - See also S. Oae, W. Tagaki, and A. Ohnu,
Tetrahedron 20,427 (1964); W. E. Truce and F. E. Roberts, J. org.
Chemistry 28, 961 (1963).
[lb] The open-chain anions (2) can be prepared in the same way;
when R = alkyl, however, the presence of a tert. amine, e.g. triethylenediamine, is necessary. The product of the reaction of (2).
R = CH3, R1 = C6H5, with benzophenone was obtained in this
way in 75 "/o yield, m.p. 153-155 "C.
[2] 1,3-Dithiane ( 3 ) , R=H, was prepared in excellent yield by
slow addition of a mixture of dimethoxymethane and 1,3-propanedithiol in chloroform to a solution of boron fluoride
etherate in chloroform at reflux. The other dithianes were made
by the general procedure reported for 1,3-dithiolanes by R. M.
Roberts and C/i.-Ch. Cheng, J. org. Chemistry 23, 963 (1958).
[3] See F. Weygand and H. Daniel, Chem. Ber. 94, 3145 (1961),
for an analogy.
[4] J. English, Jr. and P. H . Griswuld, Jr., J. Amer. chem. SOC.
67, 2039 (1945) and references cited therein; F. Weygand and
H. J. Bestmann, Chem. Ber. 90, 1230 (1957); F. Weygand, H. J.
Bestmann, and H. Ziemann, ibid. 91, 1040 (1958).
[5] B. W. Erickson, unpublished experiments in these Laboratories.
Synthesis of 1,n-Dicarbonyl Derivates Using
Carbanions from 1,3-Dithianes
By Prof. Dr. E. J. Corey and Dr. D. Seebach
Department of Chemistry, Harvard University,
Cambridge, Massachusetts (U.S.A.)
The preceeding note "1 reports the utility of bisthiocarbanions
of type ( I ) as reagents for displacement and addition reactions
at electrophilic carbon atoms to form derivatives of aldehydes and ketons. This communication deals with the
application of these carbanions to the synthesis of 1,2-, 1,3-,
and other dicarbonyl derivatives.
Treatment of the anions ( I ) of 1,3-dithianes11] with COz at
-70 "C affords the mercaptals (2) of a-keto carboxylic acids
yield. With a large excess of ethyl chloroformate
in 70-75
(Za), R' = CH,, R2 = C 0 2 H , m.p. 133-135OC
/2b), R' = t-C,H,, R2 = C02M, m.p. 98.5-99°C
(30)> R' = CH,, R2 = C0,C2H,
(36), R' = CH,C6H5, R2 = C02C2H5
(4), R' = CH,, R2 = CHO
A n g e w . C h i n . internut. Edit.
1 Vol. 4 (196s) 1 No.
Reaction of ( I ) , RI=CH3, with one equivalent of dimethylformamide or a large excess of ethyl formate at ca. -10°C
leads to the dithioketal ( 4 ) of or-oxopropionaldehyde (m.p.
of the 2,4-dinitrophenylhydrazoneof (4) : 167.5-168.5 "C).
The yield is 50-60 %. N,N-Dimethylacetamide, however,
does not react with ( I ) , R1 = CH3, under similar conditions,
and this seems to be true for higher hornologues in general.
Monomercaptals (5) of 1,2-diketones can be made from
anions of type ( I ) and carboxylic acid derivatives. In some
cases, but not generally, esters are satisfactory starting materials. Thus, the reaction of ( I ) , RI=CH3, (2 equiv.) with
ethyl cyclohexanecarboxylate gives (5a) in 60 % yield,whereas
the reaction with ethyl benzoate under the same conditions
leads t o the dimercaptal (6a), m.p. 156.5-158 OC, in 95 %
yield. The results obtained in a particular case depend on the
relative reactivities of the starting ester and the ketone
derivative (S) and the tendency of this derivative to undergo
enolate formation vs. addition in further reaction with the
anion ( I ) . The synthesis of (56) is not feasible by reaction
of ( I ) , RI-CH3, with ethyl acetate even when the anion is
added slowly to a thirty-fold excess of the ester. The chief
product is invariably the 2: 1 adduct (6b). However, the 1 : 1
adduct (5b) can be obtained in about 500/, yield by slow
addition of the anion ( I ) , RI=CH3, to excess acetyl chloride
at -70°C. Presumably the zinc or cadmium salts of ( I )
would be more satisfactory reagents for the synthesis of
structures of type (5) from acid chlorides and this point is
under investigation. The reaction of nitriles with the lithium
salts ( I ) produces the monomercaptals (5) usually without
complication; for example, (5d) was readily obtained (80 %
yield) from the anion ( I ) , RI=CH3, and benzonitrile at low
(50). R' = CH,, R2 = C6H11
(5b), R' = CH3, R2 = CH3
(5c), R' = H, R2 = CH=CH-C,H,
( 5 8 R' = CH3, R2 = CsH5
(60). R' = CH,, R2 = C,H,
/6b), R' = CH,, R2 = CH,
( 6 ~ )R'
, = H, R2 = CH=CH-C6H5
With a,@-unsaturated carbonyl compounds reaction occurs
preferentially by 1,2- rather than 1,4-addition. For example,
ethyl cinnamate and ( I ) , RI=H, (in equimolar amounts)
afford a mixture of (Sc) (1n.p. 99-100 "C) and a 1 : 2 adduct
(6c) (m.p. 176.5-177.5 "C). Alkylation of carbanions
( I ) by ketals of ct- and P-halocarbonyl compounds
XCH2CH(OR)z] represents an approach to 1,3- and 1,4-dicarbonyl structures.
Alkylation reactions furnish another route to derivatives of
1,n-dicarbonyl compounds. The 1,6-diketone derivatives (7~7)
and (76) were prepared from 1,4-dibromobutane in 84 and
89 % yield, respectively, and the 1,5-diketone derivative (7c)
was obtained from 1,3-dibrornopropane (66 % yield).
(7a), R' = H, n = 4, m.p. 102.5-103.5°C
(7b), R' = CH,, n = 4, m.p. 108.5-109°C
(7c), R' = H, n = 3 , m.p. 101.5-102°C
Finally, carbanions of type ( I ) undergo coupling under the
influence of 0xidizing:agents ,such as 1,2-dibromomethane,
Cu(lI), or iodine to afford 1,2-dicarbonyl derivatives such as
(S), m.p. 184-186°C.
To a cold (-78'C) solution of 10 mmoles of the iithium
derivative ( I ) , RI=CH3, in tetrahydrofuran 111 was added
with stirring 1.06 g (10 mmoles) of benzonitrile. The resulting
bright orange mixture was kept at -78 OC for 40 min, after
which the bath was removed and stirring was continued for
an additional 40 min. The reaction mixture was then poured
onto ice and extracted with ether. The extracts were washed
with dilute base, dried over NazS04 and concentrated t o give
2.22 g (95%) of crude imine which was hydroiysed with
150 ml of 4 "/, hydrochloric acid at 7OoC for 45 min. The
product, which partially separated as colorless crystals, was
removed by extraction with ether. After washing, drying,
of (5d),
and concentration the extract yielded 1.95 g (82
m.p. 97.8-98.7 "C. After recrystallization from methanol the
m.p. is 98.4-98.8 "C.
Received: October 5th. 1965
[Z 76/902 IE]
lead to phosphine oxides of the pyrazoline series not accessible in other ways. For Instance, by warming P-diazomethylP,P-diphenylphosphine oxide (3), R = C6H5, with methyl
vinyl ketone or dimethyl maleate in dioxane or toluene,
removal of the solvent in a vacuum, and recrystallization of
the residue from methanol we obtained the pyrazolines (6),
169'C, and (7), m.p. 153OC, in about 7 0 % yield.
Received: October IZth, 1965
[Z 82/908 IEI
German version: Angew. Chern. 77, 1138 (1965)
Synthesis and Properties of
German version: Angew. Chern. 77, 1135 (1965)
[I] E. J. Corey and D . Seebach, Angew. Chem. 77, 1134 (1965);
Angew. Chem. internat. Edit. 4 , 1075 (1965).
By Priv.-Doz. Dr. P. Boldt and Dip].-Chem. F. Vardakis
Organisch-Chemisches Institut
der Universitat GBttingen (Germany)
Diazomethylphosphine Oxides
Institut fur Pharmazeutische Chemie
der Universitat Hamburg (Germany)
i 71
By Prof. Dr. N. Kreutzkamp, Dr. E. Schmidt-Samoa, and
K. Herberg
1,4,5,8-Anthradiquinone ( I ) , which is of interest in connection with M.O. calculations of redox potentials of quinonesrll
is obtained in good yield by shaking a dioxane solution of
1,4,5,8-anthratetrol with freshly precipated silver oxide
and calcium sulfate (as drying agent) for a short time. Small
The first preparation of diazomethylphosphine oxides (3) has
been achieved by the following reactions:
For synthesis of the intermediates (Z), methanolic solutions
of the chloromethyl compounds ( I ) were saturated with NH3
at 0°C and heated for 5 h in an autoclave at 130OC. The
residues were taken u p in chloroform and extracted several
times with dilute sulfuric acid. The compounds (2) were
precipitated from the extracts by alkali and recrystallized
several times from benzene/ether. Their conversion into (3)
was effected by adding sodium nitrite to their solutions in
glacial acetic acid, with ice-cooling, whereupon the diazomethylphosphine oxides separated. Thus, P,P-dibenzyl-Pdiazomethylphosphine oxide (3), R = C7H7, m.p. 99 OC, was
formed immediately in 90 yield from P-aminomethyl-P,Pdibenzylphosphine oxide (2), R = C7H7, m.p. = 112 "C, and
1 mole of sodium nitrite in glacial acetic acid; P-diazomethylP,P-diphenylphosphine oxide (3), R = C6H5, m.p. = 56 "C,
was obtained analogously in 70 % yield from P-aminomethylP,P-diphenylphosphine oxide (2), R = C6H5, m.p. = 101 "C.
Both the diazomethyl compounds are very stable and intensely yellow. On addition of hydrochloric acid t o their
methanol solutions they are converted into the chloromethylphosphine oxides ( I ) , and they react with triphenylphosphine
t o give phosphazines (4) which crystallize from the solution.
amounts of 5,8-dihydroxy-l,4-anthraquinoneformed at the
same time can be removed chromatographically (chloroform/ethyl acetate, neutral silica gel).
The constitution of the diquinone ( I ) (yellow needles from
dioxane/cyclohexane; decomp. at 170 "C) follows from
elemental analysis, the ultraviolet spectrum (Arna, = 353 mlp;
= 3750 in dimethylformamide), the N M R spectrum
(2 singlets at -7.22 and -8.80 ppm, relative intensity
2: 1 [21), and the simple infrared spectrum (strong bands at
1667,1600,1271,1124, and 849 cm-1 in KBr). The compound
( 1 ) has a higher redox potential (+736 mV in 9 0 % acetic
acid containing 3 % of dimethylformamide) than 1,2,5,6anthradiquinone [31, decomposes in aqueous alkali (in
contrast to the 1,2,5,6-diquinone), and reacts readily with
nucleophiles. Repeated treatment with aziridine and subsequent dehydrogenation with silver oxide affords 2,7-di- and
2,6,7-tri-aziridino-1,4,5,8-anthradiquinone(proof of structure by elemental analysis and N M R spectroscopy).
On oxidation with one equivalent of silver oxide, 1,4,5,8anthratetrol, which is cccessible by alkaline hydrolysis of
its acetate [41 with exclusion of air, affords 5,8-dihydroxy1,Canthraquinone 151 (colorless leaflets from butanoi; decamp. at 300°C) as main product. By oxidation of 1,4,5anthratriol (yellow prisms from acetone; decomp. at 230 " C ) ,
accessible from its acetateC41, with silver oxide in acetone we
obtained 5-hydroxy-l,4-anthraquinone (red needles from
ch1oroform;ethyl acetate; decomp. at 220 "C).
Received: October l l t h , 1965
[ Z 87/919 IEI
German version: Angew. Chern. 77, 1137 (1965)
These products ( 4 ) are hydrolysed when heated with 80%
ethanol, affording the phosphinyiformaldehyde hydrazones
(5) which, after removal of the alcohol, are separated by
means of chloroform/water from the triphenylphosphine
oxides that are formed simultaneously.
Of preparative interest are the addition reactions of the diazomethylphosphine oxides t o unsaturated compounds, which
[l] M . G . Evans, J. Gergely, and J . de Heer, Trans. Faraday SOC.
45, 312 (1949); S. Weckherlin and P. Boldr, unpublished work.
[ 2 ] In deuteriochloroform. Internal standard: tetramethylsilane
0 ppm.
131 P. Boldt, Naturwissenschaften 51, 137 (1964).
[4] H . Brockmann and G. Budde, Chem. Ber. 86, 432 (1953).
[5] Y. Lepage, Bull. Soc. chim. France 1963, 1141.
Angew. Chem. internat. Edit.
Val. 4 (1965)
1 Arc. 12
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using, synthesis, carbanion, dicarbonyl, dithiane, derivaten
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