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I t has been found that the acid chlorides of several aromatic acids on treatment with silver oxide and bromine in carbon
tetrachloride solution loose carbon dioxide. The acid chloride is substituted by the halide.
It has been reported3 that when the acid chlorides like the sugar acid chlorides, would react to form
of acetylated hexonic acids are dissolved in carbon carbon dioxide and the corresponding halide.
tetrachloride and heated at reflux temperature with Benzoyl chloride was found to react, with silver
silver oxide and bromine, the acid chloride loses car- oxide and bromine to yield bromobenzene. The m-
bon dioxide and forms the aldehpdo-l-bromo-penta- and p-nitrobenzoyl chlorides formed the corre-
0-acetyl-pentose. Either acetic anhydride or ace- sponding rn- and p-bromonitrobenzenes. Kaph-
tyl chloride3react with mixtures of silver oxide and thoyl chloride also reacted, although slowly, under
bromine and after respectively losing 2 moles and 1 the same conditions to form bromonaphthalene.
mole of carbon dioxide, form methyl bromide. The reaction as measured by the evolution of car-
Although the product formed by the reaction of bon dioxide was essentially quantitative (Table I).
acid chlorides with silver oxide and bromine is es- A possible mechanism for the above reaction is
sentially the same as that obtained by the decar- that the acid chloride reacts with silver oxide to
boxylation of the silver salts of organic acids by re- form the silver salt of the acid and silver chloride.
action with bromine,4 the acid chlorides, in contrast The silver salt would then react with bromine to
TABLE I
OF AROMATIC
DECARBOXYLATION ACID CHLORIDES
WITH BROMINE
A N D SILVER
OXIDE
COZevolved.
Equivalent in
Weight, ml. 0.1 N HCl Compound" w p . , OC.
Compound g. Calc'd Obsv'd Isolated Observed Literature
~~ ~ ~
A Convenient Synthesis of Alkyl Halides from mercuric oxide, and reaction in light gives poly-
Carboxylic Acids bromination.
When either exo- (I) or endo-5,6,7,8,9,9-hexa-
Sir: ch10ro-1,2,3,4,4a15,8,8a-octahydro-exo-endo 1,4,5,8- -
dimethano-2-naphthoic acid (11)2was treated under
The salts of R variety of metals and carboxylic these conditions, a mixture of 71% em-(111) and
acids upon treatment with halogens lead to the 29% endo-bromides (IV)z was formed. This is
halogenative decarboxylation reaction RCOOM +
precisely the same mixt,ure of bromides obtained
+ +
X,+ RX MX CO,.' Of these reactions, that from the silver salt of either acid with bromine.2
of the silver salt (generally termed the Hunsdiecker This suggests that both procedures lead to the same
reaction) appears to be the most useful.' This intermediate RCOOX. The reaction may involve
reaction has the practical disadvantage that the the existence of the mercuric salt although (a) it has
silver salt must be relatively pure and must be been reportedla that mercury salts of acids such as
scrupulously dry in order to obtain satisfactory stearic acid do not give good yields following the
yields. In the course of our studies2 on the mecha- normal Hunsdiecker reaction, and (b) glutaric
nism of the decomposition of the acyl hypobromite acid does not. give ybutyrolactone, whereas the
intermediate' in the Hunsdiecker reaction, we a b silver (and presumably the mercury) salt gives the
tempted to prepare this intermediate in another lactone. It seems most likely that the mercuric oxide
fashion. This has led to what appears to us to be a gives a positive halogen species: which reacts with
useful preparative method, as reagents and opera- the carboxylic acid to give the acyl hypohalite.
tions are much more convenient than the silver If this is the case, and if equation (1) represents the
salt-bromine reaction. stoichiometry of the reaction, we do not under-
Treatment of a slurry of excess red mercuric stand why the water formed does not interfere
oxide in a refluxing solution of an aliphatic car- with the reaction as it apparently does in the Huns-
boxylic acid in carbon tetrachloride with approxi- diecker procedure where glassware and chemicals
mately one equivalent of bromine in the dark led to need to be scrupulously dry.' I n any case, the pre-
excellent yields of the corresponding alkyl bromide. parative value of this procedure lies in its conven-
For example, treatment of 0.25 mole of stearic acid ience and simplicity in comparison to those proce-
with 0.25 mole of bromine and 0.19 mole of red dures involving preparation of silver or mercury
mercuric oxide in 150 ml. of carbon tetrachloride for salts.
one hour gave a 93% yield of crude heptadecyl
bromide, m.p. 22" ( l k 3m.p. 32" for pure material).
The presumable stoichiometric equation is as "3
follows:
the crude product produced recovered alcohol, 198 g. of 1,1,7-tri- form containing 0.02 mole of titanium tetrachloride for 5 hr. a t
hydroperfluoroheptyl benzoate, b.p. 155"(0.5mm.), and 295 g. of 50'. After work-up similar to above experiments, fractionation
1,1,7-trihydroperfluoroheptyl orthebenzoate, b.p. 187" (0.1 of the product yielded 24.2 g. (80%) of the methyl fluoro alcohol
mm.), 62ycyield based on unrecovered alcohol. carbonate, b.p. 46" (0.1 mm.).
Anal. Calcd. for C28H14F3803: C, 31.05; H, 1.29. Found: The two methyl fluoro alcohol carbonates from these experi-
C, 31.21; H, 1.36. ments were found to be identical by infrared and n.m.r. analyses
l,l,S-TrihydroperfluoropentylCh1orocarbonate.-A solution of and determination of the same retention times by g.1.p.c.
69.6 g. (0.3mole) of 1,1,5-trihydroperfluoropentanoland 5.4 g. 1,1,7-Trihydroperfluoroheptylchlorocarbonate was prepared in
(0.3mole) of water was added intermittently over a period of 1.25 a similar manner except the alcohol and water were added por-
hr. to a mixture of 26.4 g. of ferric chloride in 60 ml. of carbon tionwise simultaneously. The chlorocarbonate was obtained
tetrachloride a t 76". Large amounts of phosgene and hydrogen in 40% yield, b.p. 73" (14mm.).
chloride were evolved over a period of 5 hr. After the addition of Anal. Calcd. for C8H3ClF1202: C, 27.70; H, 1.54. Found:
2.5 ml. more of water, the reaction was allowed to continue an C, 27.81; H, 1.44.
additional 8 hr. After cooling, the entire reaction mixture was Phosgene was bubbled through a mixture of 22.7g. (0.1mole) of
dissolved in ether, washed very quickly with cold water, dried, 1,1,5-trihydroperfluoropentanoland 8.1 g. (0.05 mole) of ferric
and distilled. The fractionation gave recovered alcohol, 40 g. chloride for 6 hr. a t 50". Less than 10% of chlorocarbonate was
(6097,)of the chlorocarbonate, b.p. 53" (13 mm.), and 15 g. obtained.
(217,) of the bis carbonate.
A part of the 1,1,5-trihydroperfluoropentyl chlorocarbonate Acknowledgment.-This paper is related to an obser-
(6.0 g., 0.02 mole) was added to excess methanol in ether a t 50". vation by one of us (M. E. H.) at the U. S. Naval
Distillation after work-up yielded 4.3 g. (70y0of methyl 1,1,5- Ordnance Laboratory, Silver Spring, Maryland. The
trihydroperfluoropentyl carbonate, b.p. 50' (0.15mm.).
Methyl chlorocarbonate (10.4 g., 0.11 mole) was stirred with many stimulating discussions with Dr. D. V. Sickman
23.2 g. (0.1 mole) of 1,1,5-trihydroperfluoropentanolin chloro- and Dr. 0. H. Johnson are gratefully acknowledged.
Bromodecarboxylation of organic acids by the Cristol-Firth modification of the Hundsiecker reaction using
the free acid and red mercuric oxide was found to be much more effective than the modification using the acid
chloride and silver oxide. A study has been made of the possible use of oxides other than mercuric oxide and
of the effectiveness of various solvents.
Replacement of the carboxyl group in organic acids oyl chloride, p-nitrobenzoyl chloride, and p-chloro-
by a halogen atom, especially bromine, by treatment of benzoyl chloride.
the anhydrous silver salt of the acid with bromine, The silver oxide was carefully dried as was all the
chlorine, or iodine in an inert solvent is commonly glassware and the carbon tetrachloride, bromine, and
known as the Hunsdiecker r e a c t i ~ n . ~ -Yields
~ are acid chlorides were redistilled before use. Although
generally quite good (usually better than 60%), but numerous variations of the reaction conditions were
the reaction is extremely sensitive to trace amounts of tried, only trace amounts of the desire(. bromides
water, tlle presence of which leads to the recovery of were obtained by fractional distillation of the reaction
unchanged acid. Unfortunately, the preparation of mixtures. However, fair yields of bromobenzene were
dry silver salts of carboxylic acids is frequently very obtained from silver benzoate by the original Huns-
difficult and, because such salts are usually quite sensi- diecker reaction.
tive to heat also, they are &n quite hard to dry Fund, Cristol, and Firth have reported' that treat-
thoroughly. ment of a slurry of excess red mercuric oxide in a re-
Several years ago there appeared a report5 that the fluxing solution of stearic acid in carbon tetrachloride
acid chloride of penta-0-acetyl-D-gluconic acid under- with approximately an equivalent amount of bromine
goes smooth decarboxylation when heated with bro- in the dark gave a 93% yield of crude heptadecyl
mine and silver oxide in carbon tetrachloride, furnish- bromide. The reaction also was reported to give
ing aldehydo-1-bromo-D-arabinose penta-0-acetate in poor yields with benzoic acid arid glutaric acids, and
an excellent yield. A second report6 described the fair to excellent yields with cyclopropanecarboxylic
reactions of benzoyl chloride and three other aromatic acid, 9,lO-dihydro-9,lO-ethane-9-ant hronic acid, and
acid chlorides with bromine and silver oxide in carbon lauric acid. As soon as we learned of the Cristol-Firth
tetrachloride. modification, its apparent convenience and simplicity
An investigation of this modification of the Huns- in comparison to those procedures involving prepara-
diecker reaction was started using the following acid tion of silver salts or acid chlorides immediately sug-
chlorides: benzoyl chloride, n-butyryl chloride, phthal- gested a broad study of this modified procedure using
different classes of carboxylic acids and the use of
(1) (a) This work was made possible b y Grant R897-B from the Petroleum solvents other than carbon tetrachloride. Since mer-
Research Fund, administered by the American Chemical Society: (b)
American Chemical Society Petroleum Research Fund Scholar.
curic oxide is relatively expensive and mercury com-
(2) R. G. Johnson and R . K . Ingham, Chem. Rev., S6, 219 (1956). pounds are tokic, a study also was made of the possi-
(3) C. V. Wilson, Org. Reactions, 9 , 332 (1957). bility of using other oxides for this reaction.
(4) C. W. Shoppee and R . J. Stephenson, J . Chem. Soc., 2230 (1954).
(5) F. A. H . Rice, .I. A m . Chem. Soc., 7 8 , 3173 (1956).
(6) F. A. H. Rice and W. Morganroth, J . O w . Chem., 11, 1388 (1956). (7) Stanley J. Cristol and William C. Firth, Jr., i b i d . , 96, 280 (1961)
416 DAVIS,HERYNK,
CARROLL,
BUNDS,AND JOHNSON VOL.30
TABLEI
PERCENTYIELDSBASEDO N WEIQHTOF BROMIDE
RECOVERED
Acid Solvent Product Yield, 7
'0 B.p., OC." nDOC.a
Decanedioic 66 79 -Yield, %-
HgO
Using red mercuric oxide and either carbon tetrachloride or b-1-
lll,2,2-tetrachloroethaneaa solvent. Numbers in parentheses Acid low) AgnO PbO Pbso4 CdO
are per cent yields baaed upon the amount of organic bromide Propionic 87 78 42 45 8
recovered by fractional distillation. Palmitic 76 12 5 (CClr)
Acid chlorides
After trying a number of variations of the method, Benzoyl chloride 7 (CCla)
it was found that best yields were obtained when the Palmitoyl chloride 8 (cc4)
acid, the red mercuric oxide, and the solvent were Butyryl chloride 45
mixed and stirred with a magnetic stirrer. The mix- a Using 1,1,2,2-tetrachloroethaneaa solvent and oxides other
ture was then heated and a small fraction of the bro- than red mercuric oxide.
mine was added. If a reaction did not occur spon-
taneously, heating was continued until the reaction For the effectiveness of solvents other than carbon
started; then the remainder of the bromine was slowly tetrachloride and tetrachloroethane see Table IV.
added. The mixture was kept warm for 1 hr., then
filtered and washed with 5y0sodium hydroxide solution, Discussion
then with water, and dried over anhydrous magnesium
sulfate. It was then filtered and the bromide was In this investigation it was found that the Cristol-
separated by fractional distillation and identified by its Firth method using red mercuric oxide and the free acid
boiling point and refractive index (see Table I). gave much more decarboxylation than did the method
FEBRUARY
1965 p31-Hl COUPLING
FOR STRUCTURE
DETERMINATION 417
TABLEIV least 1 hr., then filtered, washed, and dried, and the organic
bromide was separated by fractional distillation. The prepara-
OF CARBON
PERCENTYIELDSBASEDON AMOUNT DIOXIDE
tion of 1-bromohexane is typical of the method used.
PRODUCED' Preparation of I-Bromohexane from Heptanoic Acid.-A few
Yield, $' & drops of a solution containing 16 g. (0.1 mole) of bromine in 50
Nitro- Bromo- Chloro-
ml. of dry carbon tetrachloride produced an immediate reaction
Ben- ben- ben- ben- CzClr- C&la- Hex-
Acid zene nene zene nene Fz F3 ane
when added to a warm, stirred mixture of 13.0 g. (0.1 mole) of
heptanoic acid and 22 g. of red mercurir oxide in 150 ml. of dry
Palmitic 69 82 76 67 71 58 40 carbon tetrachloride. The remainder of the bromine solution was
Phthalic 0 0 32 added slowly and the reaction mixture was refluxed for 1 hr.
Terephthalic 26 The mixture was then filtered, washed with 5y0 sodium hy-
Propionic 79 61 2 40 droxide solution and then with water, and dried with anhydrous
Benzoic 6 48 41 0 magnesium sulfate. Careful fractional distillation of the solution
Stearic 81 gave 6 g. of I-bromohexane, b.p. 150-159", 12% 1.4470.
2-Ethylbutyric 60 43 To determine the per cent yield based on the amount of
carbon dioxide produced, 2 ml. of bromine was slowly added to a
a Using red mercuric oxide and different solvents.
warm, stirred mixture containing 50 ml. of solvent, 0.01 mole of
acid, and 5 g. of red mercuric oxide in a 500-ml., three-neck
using silver oxide and the acid chloride. The Cristol- flask. The flask was fitted with a dry nitrogen inlet, separatory
funnel for addition of the bromine, and a reflux condenser. The
Firth method is simpler than the original Hunsdiecker carbon dioxide produced was swept out of the flask by nitrogen
method in that it does not require the preparation of the and passed through three Dry Ice traps to remove all bromine
dry silver salt. In many cases higher yields were ob- vapor and then absorbed in standard barium hydroxide solution.
tained with tetrachloroethane as solvent than with car- The barium carbonate precipitate was filtered off and the excess
barium hydroxide was titrated with standard acid. The follow-
bon tetrachloride. This probably was due to the higher ing is typical of the method used.
boiling point of the tetrachloroethane which permitted a Bromodecarboxylation of Palmitic Acid.-Bromine (2 ml.)
higher reaction temperature. Bromobenzene and tet- was added slowly to a warm, stirred mixture containing 50 ml.
rachlorodifluoroethane seem to offer soine promise as of carbon tetrachloride, 2.564 g. (0.01 mole) of palmitic acid,
other solvents for this reaction. Yellow mercuric oxide and 5 g. of red mercuric oxide. The carbon dioxide pro-
duced was swept out of the flask by nitrogen and absorbed in
was found to be almost as effective as red mercuric 125.0 ml. of standard 0.2 N barium hydroxide solution. The
oxide. As a general rule aromatic and dicarboxylic barium carbonate precipitate was filtered off and the excess
acids underwent less bromodecarboxylation than did barium hydroxide titrated with standard hydrochloric acid,
aliphatic monocarboxylic acids. yielding 0.0090 (goyo) mole of carbon dioxide.
Acknowledgment.-Acknowledgment is made to the
Experimental donors of The Petroleum Research Fund, administered
by the American Chemical Society, for support of this
For the preparation and isolation of the organic bromides, 0.1 research and to the E. 1. du Pant de Nelllours and
mole of bromine was slowly added to a warm, stirred mixture of
0.1 mole of acid and 0.1 mole of red mercuric oxide in 150 to 200 Company for furnishing samples of tetrachlorodifluoro-
ml. of ,solvent. The reaction mixture was then refluxed for a t ethane and trichlorotrifluoroethane.
benzylidenebenzylamine (1) are known to produce a red of imine 1 (in excess) in 10 mL of solvent (see Table I). A strong
purple color? and this coloration remains intense as long crimson color appeared immediately with the addition of or-
as carbanion is present in the solution. We used this ganolithium; the solution was then titrated by a 1 M solution of
property for the analysis of organolithium reagents by two sec-butyl alcohol in xylene or a 1 M solution of benzoic acid in
methods (see Scheme I). tetrahydrofuran.
Method B. A 5-mL aliquot of the solution to be analyzed was
In method A, the organolithium reacts with a solution added at room temperature under nitrogen t,o a solution of 2 mL
of an excess of the Schiff base 1 by addition and meta- of diisopropylamine (in excess) in 10 mL of solvent (see Table
lation. The colored anion 3 is obtained by metalation of I). Imine 1 (2-3 drops) was added to this mixture, and the crimson
the Schiff base by means of RLi or the lithium amide 2 color appeared immediately. The solution was then titrated as
formed by addition. In method B, the organolithium is in method A.
converted to lithium diisopropylamide (4), which produces In the two methods, the end point was reached when the color
anion 3 from a few drops of Schiff base 1. The lithium of the solution became a persistent yellow.
compound RLi is quantitatively transformed into 2 and Registry No. 1, 780-25-6;n-BuLi, 109-72-8;sec-BuLi, 598-30-1;
3 (method A) or 4 and 3 (method B). Titration is made t-BuLi, 594-19-4;PhLi, 591-51-5.
by addition of an acid solution which reacts both with the
lithium amide 2 or 4, and with the colored anion 3. At the
end point, the added acid is equal to the initial quantity
of RLi. Results are summarized in Table I.
These methods have the advantage of using organo- Photoassisted Cristol-Firth-Hunsdiecker
lithium compounds in the common conditions of use of Reaction
these reagents in various solvents such as diethyl ether,
tetrahydrofuran, benzene, and hexane. These are single A. I. Meyers* and Michael P. Fleming‘
titrations, simple and rapid to realize in the laboratory,
and present a sharp and easy to observe end point. The Department of Chemistry, Colorado State University,
Fort Collins, Colorado 80523
Schiff base 1, easily prepared from benzylamine and
b e n ~ a l d e h y d e ,is~a, ~liquid at room temperature and can Received March 28, 1979
be stored as a solid at -30 OC. Finally, these methods can
be used to control the quality of the solvents.8 A well-known route to aryl and alkyl bromides is the
Hunsdiecker reaction2 or its more recent modification by
Experimental Section Cristol and Firth.3 The latter workers found that mercuric
Solvents were drit?d on molecular sieves, then distilled from salts of carboxylic acids could replace the more tediously
LiAIHl prior to use. prepared and sensitive silver salts in the key bromo-
Method A. A 5-mL aliquot of the solution to be analyzed was decarboxylation step upon treatment with bromine.
added a t room temperature under nitrogen to a solution of 2 g Recent studies on the scope and mechanism4* of the
Cristol-Firth modification indicate that the carboxylic
(6) (a) T. Kauffmanr,, K. Habersaat, and E. Koppelmann, Chem. Ber.,
110,638 (1977). (b) L. I. Sivova, N. A. Sivov, R. A. Gracheva, and V. M.
Potapov, Zh. Org. Khin., 14, 791 (1978). (1) National Service Award (NIH) Postdoctoral Fellow, IF32CA
(7) For a review see for example: R. W. Layer, Chem. Reu., 63, 489 05946-02.
(1963). (2) Wilson, C. V. Org. React. 1957, 9, 341.
(8) For example, titrations (method A) by an identical acid solution (3) Cristol, S. J.: Firth. W. C.. Jr. J. Ore. Chem. 1961. 26. 280
of an identical solution of n-BuLilhexane in THF freshly distilled from (4) Davis, J. A.; Hernyk, J.;Carroll, S.; Bunds, J.; Johnson, D. J . Org.
LAM4and THF distilled some months prior to the experimentationyielded Chem. 1965,30, 415.
N = 1.69 and N = 1.59, respectively. The difference between these two ( 5 ) Bunce, N . J. J . Org. Chem. 1972, 37, 664.
values is attributed to impurities contained in “old” THF. (6) Cason, J.; Walba, D. J . Org. Chem. 1972, 37, 669.
3.5-(NO., LC,H,CO,H 97 Oe
3~NO,-4%l-~-MeOd6H,CO,H 9 6c -40
m-BrC,H,CO,H 83
p - Br C, H,CO, 13 86 Maximum Optical Rotation of 2-Fluorooctane?
o-CIC,H,CO,H 81 Survey of Fluorinating Reagents
m-ClC, H, CO, H 75
o-MeOC,H,CO,H d Jacques Leroy,la Eric Hebert,lb and Claude Wakselman'"*
o-phthalic acid 42 8 5f
1-naphthoic acid d C.N.R.S., 94320 Thiais, France
n-C, ,H,,CO,H 99 9lf
n-C, ,H,,CO,H 90 90f Received March 28, 1979
11-C,,H,,CO,H 85 95f
a Reactions run in carbon tetrachloride a t reflux, molar Optically active 2-alkyl halides are of particular interest
ratios of RC0,H-HgO-Br, are 1.00:1.50:1.50, respective- as they can serve as models in the study of numerous
ly. All yields are for pure (distilled o r crystallized) pro- reactions of organic chemistry. 2-Chloro-, 2-bromo-, or
ducts and were identified by comparison with published 2-iodooctaneis commonly used2 and their optical purities
IR and NMR data (Aldrich or Sadtler). J. M. Kane and
A. I. Meyers, Tetrahedron Lett., 771 (1977). Gave only are determined without ambig~ity.~ By contrast, however,
polybrominated products. e See ref 5. Based on car- the maximum optical rotation of 2-fluorooctane remains
bon dioxide produced. Actual isolated yields were much unknown, as no chemical correlation has been established,
lower in those instances where isolation was attempted owing to the poor leaving-group character of fluorine.
(see ref 4). Thus, only an estimate of optical purity has been made
for 2-fluorooctane (1) based on a correlation between
acids form a diacyloxy mercury salt 1, which then leads molecular rotation and bond refra~tion.~
to the acyl hypobromite 2 followed by thermal decom- Recent results obtained with methyltri-n-butylfluoro-
position to the alkyl bromide. During the course of other phosphorane5 (2) leading to 2-fluorooctane of higher optical
2RCOzH ---
HgO
(RCOZ),Hg
1
-ZBQ
2RC02Br 2RBr
2
- rotation than that of San Filippo and Romano4 (stated as
about 100% optical purity) have prompted us to check
other fluorinating reagents.6 Phenyltetrafluoro-
studies, we had occasion to investigate the CFH reaction phosphorane7 (3), N - (2-chloro-1,1,2-trifluoroethy1)di-
with aromatic acids. The observed trend@ is that aromatic ethylamine8 (4) (FAR), and (diethy1amino)sulfur tri-
acids form rather insoluble mercuric salts and give lower fluorideg ( 5 ) (DAST) were used according to slightly
yields than aliphatic acids. We now describe a further modified procedures.
modification of the CFH reaction which simply involves CGH,,CH(OTs)CH3 + (n-C4Hg)3PFCH, +
71001-78-0; m-BrC6H4Co2H,585-76-2; p-BrC6H,CO2H, 586-76-5; (8) C. M. Sharts and W. A. Sheppard, Org. React., 21, 125 (1974).
O-CIC&~CO~H, 118-91-2;m-ClC&C02H, 535-80-8; o-Me0C&I4CO2H, (9) W. J. Middleton, J . Org. Chem., 40, 5'74 (1975).