Bäuml, Englbert

Mayr, Herbert

English

Crossref

Diels-Alder reactions of 2-alkynoyl chlorides with cyclopentadiene: a reinvestigation

Universität München: Elektronischen Publikationen

2600 J .  Org. Chem. 1983,48, 2600-2601 
in the syringe and injected into 3.00 mL of an aqueous solution 
containing 0.0091 N HCl and 0.017 M KCl. The temperature of 
the solution was maintained a t  60 “C by using a water bath, and 
the procedure was performed inside an enclosure containing a 
nitrogen atmosphere. Another aqueous solution was prepared 
which contained 0.02 M Tris in the free base form, and 2 X 
M 1. After equal volumes of these two solutions were mixed in 
the stopped-flow spectrophotometer, the final pH was measured 
as 7.50. After correction for a 0.025-mL holdup in the injection 
syringe, the final concentration of 2 was calculated to be 5.02 x 
lo4 M and that of 3 to be 5.00 X lo4 M. In all experiments, the 
ionic strength of the mixed solution was calculated to be 0.01 f 
0.003, disregarding the contribution of the surfactant to the ionic 
strength. 
Kinetic Studies. Reactions were monitored with a Durrum 
Model D-130 stopped-flow spectrophotometer equipped with a 
Beckmann Model DU-2 monochromater and a Tektronix Model 
5103N/D15 storage oscilloscope. The oscilloscope readout was 
photographed by using a Polaroid camera. A constant-temper- 
ature circulating bath maintained the temperature at 25 * 0.2 
“C. The appearance of the Ells- product was followed a t  445 
nm.13b All reactions were monitored with two oscilloscope time 
bases, one appropriate to the faster reactions and one appropriate 
to the slower reactions. Rate constants were calculated from the 
appropriate traces. First-order kinetic behavior was observed for 
the fastest reaction, with correlation coefficients greater than 0.999 
for computer-generated correlations of log (Al- - At) with time. 
The fastest reaction was rapid enough so that product oxidation 
could be ignored. 
The rate of the second reaction in Scheme I was in all cases 
comparable to the rate of product oxidation. The relative rate 
constants for the second reaction were therefore calculated from 
the maximum product concentrations observed. The relative 
maximum concentration from the second step, B, was obtained 
by subtracting from the maximum observed concentration that 
amount of product that was due to the first step (1 X 10” M) and 
then dividing the result by the theoretical total product yield from 
the second step (also 1 X M). If k, is the pseudo-first-order 
rate constant for the second step in Scheme I and k,, is the 
pseudo-first-order rate constant for product oxidation, then 8, 
can be approximated by (k,,/k,,) raised to the power kOx/(k , ,  - 
The ratio between k,, and k, was then calculated for 0- 
in each case. On the assumption that k,, was the same in each 
case, the “ratio of ratios” thus gave the relative rate constants 
for the second step at different thiol  concentration^.^^ 
The estimate of k, was obtained from measurement of the time 
at which 8, was observed, T ,  in the experiment with 0.001 M 
2. By use of the above rate constants, T- can be approximated 
by (l/(ko, - k,&) In (kox/k+2).22 The nature of the absorption vs. 
time reaction trace was such that a precise T~~ value was not 
obtained; nevertheless T, lay between 10 and 100 s. Using these 
two boundary values and the relation k,, = 0.138 k,, (from 
the 8, value), we calculated that 0.0032 8-l < k,, < 0.032 s-l; 
we thus estimate that 12, < 32 L mol-l 5-l. 
The occurrence of the oxidation reaction, which forces us to 
resort to the foregoing analysis, cannot be easily prevented. The 
vesicles were prepared in a nitrogen atmosphere, but oxygen is 
apparently introduced during the transfer of the solutions to the 
stopped-flow spectrophotometer. We suspect that only be en- 
closing that instrument in a nitrogen atmosphere, and thus 
performing the entire experiment under an inert atmosphere, 
could we completely eliminate the complication of product oxi- 
dation. 
Acknowledgment. I thank Professor Robert A. Moss 
for helpful discussions and Professor Jean-Marie Lehn for 
assistance in preparing this paper. Financial support from 
(22) Moore, J. W.; Pearson, R. G. “Kinetics and Mechanism”, 3rd ed.; 
Wiley: New York, 1981; p 290 ff. 
(23) It must be noted that this is a crude calculation; the relations used 
are exactly true only for two consecutive frat-order reactions. The system 
we observed involved two parallel pseudo-first-order reactions, followed 
by a third, consecutive pseudo-first-order reaction. There is no simple 
kinetic solution which can analyze completely such a system. Therefore, 
the initial reaction has been ignored, because it is much more rapid than 
the two reactions which follow. 
0022-326318311948-2600$01.50/0 
the National Science Foundation is also gratefully ac- 
knowledged. 
Registry No. 1, 69-78-3; 2, 79246-00-7; 3, 70755-47-4; (n- 
C16H33)2N+(CH3)CH2CHzSSEll, 85908-82-3. 
Diels-Alder Reactions of 2-Alkynoyl Chlorides 
with Cyclopentadiene: A Reinvestigation 
Englbert Biiuml and Herbert Mayr* 
Institut fur Organische Chemie der 
Friedrich- Alexander- Uniuersitat Erlangen-Nurnberg, 
0-8520 Erlangen, Federal Republic of Germany 
Received November 16, 1982 
Diels-Alder reactions of cyclopentadiene represent a 
simple access to the bicyclo[2.2.1] skeleton.la While 
electron-deficient alkenes react readily with cyclo- 
pentadiene,lblc cycloadditions to triple bonds appear to be 
problematic. 
While alkenoyl chlorides are among the most reactive 
dienophiles,’bpc phenylpropynoyl chloride has been reported 
“not to undergo appreciable reaction with cyclopentadiene 
at  room temperature even after 24 hSe2 Therefore, Baum 
and Viehe used a route via acetylenic iminium salts for 
synthesizing compounds of type 4.3 In earlier papers, 
however, Diels-Alder reactions of la with cyclopentadiene 
have been r e p ~ r t e d . ~ ~ ~  Forty-one percent of cycloadduct 
was obtained when a solution of la and 2 in toluene was 
heated at  reflux for 48 h.4 Other workers describe a 
spontaneous reaction of la with 2 at room temperature in 
the presence of a “few crystals of picric acidne5 The in- 
consistency of these reporta prompted us to reexamine the 
reactions of alkynoyl chlorides with cyclopentadiene. 
When la and 2 were mixed at 0 “C, warmed up to room 
temperature, and poured into a suspension of sodium 
bicarbonate in methanol, 84% of ester 4a was obtained. 
Combining these cycloaddends without external cooling 
resulted in a rapid exothermic cycloaddition reaction ac- 
companied by partial polymerization of cyclopentadiene. 
Alkynoyl chlorides lb and IC reacted with cyclopentadiene 
at room temperature to give good yields of norbornadienes 
4b and 4c, respectively. Because of the mild reaction 
\ 
2 COCl  COZCHJ l a ,  R = Ph 
b, R = CH, 3 4a, 84% 
c, R = C(CH,), b, 78% 
c, 82% 
conditions employed for these cycloadditions6 and the 
versatile reactivity of acid chlorides 3, we consider the title 
reaction as the method of choice for the synthesis of any 
~~~ 
(1) (a) Sauer, J. Angew. Chem., Int. Ed.  Engl. 1966,5,211. (b) Sauer, 
J.; Wiest, H.; Mielert, A. 2. Naturforsch., B: Anorg. Chem., Org. Chem., 
Biochem., Biophys. Biol. 1962,17,203. (c) Sauer, J. Angew. Chem., Int. 
Ed.  Engl. 1967,6, 16. 
(2) Glass, R. S.; Smith, D. L. J. Org. Chem. 1974, 39, 3712. 
(3) Baum, J. S.; Viehe, H. G. J. Org. Chem. 1976, 41, 183. 
(4) Cristol, S. J.; LaLonde, R. T. J. Am. Chem. SOC. 1959,81, 5417. 
(5) P m ,  G. I.; Kleis, J.; Wittekind, R. R.; Rosenau, J. D. J. Org. Chem. 
1961,26,4898. 
(6) Diels-Alder reaction of 2-butynoic acid with cyclopentadiene is 
carried out a t  185 OC: Simmross, F.-M.; Weyerstahl, P. Liebigs Ann. 
Chem. 1981, 1089. 
0 1983 American Chemical Society 
J.  Org. Chem. 1983, 48, 2601-2603 2601 
norbornadiene-2-carboxylic acid derivatives. Since even 
the sterically hindered tertiary butyl compound IC reacts 
readily a t  room temperature, this reaction should be of 
general applicability. 
Experimental Section 
General Procedures. Infrared spectra were recorded on a 
Beckman Acculab 1 IR spectrophotometer. 'H NMR spectra were 
taken in carbon tetrachloride on a JEOL JNM-C-60-HL spec- 
trometer, and mass spectra were recorded on a Varian MAT CH 
4 spectrometer. 
Methyl 3-Phenylbicyclo[2.2.l]hepta-2,5-diene-2- 
carboxylate (4a). Cyclopentadiene (2.70 g, 40.9 "01) was added 
to precooled (0 "C) phenylpropynoyl chloride (la;' 6.00 g, 36.5 
mmol) in a nitrogen atmosphere and the mixture was allowed to 
warm to 20 "C within 4 h. After 10 h, more cyclopentadiene (2.70 
g, 40.9 mmol) was added. After the mixture was stirred for 24 
h, la was consumed completely (monitoring by NMR) and the 
mixture was added slowly to a suspension of NaHC03 (3.5 g) in 
50 mL of methanol. After 1 h, the mixture was filtered and the 
solvent evaporated. The residue was dissolved in 20 mL of ether 
and filtered, the ether evaporated, and the residue distilled: 6.93 
g (84%) of 4a; bp 109-110 "C (0.2 mmHg) [lit.4 bp 111-116 "C 
(0.6 mmHg)]; IR (neat) 3050,2980,2940,2870, 1705, 1605,1590, 
1485,1425, 1330,1290, 1230,1185, 1145,1095,1080,1070,755, 
715, 690 cm-'; 'H NMR (CC14) 6 2.03, 2.23 (br AB system, J = 
7 Hz, 2 H), 3.60 (s, 1 H), 3.82 (br s, 1 H), 4.03 (br s, 1 H), 6.94 
(br s, 2 H), 7.1-7.7 (m, 5 H); mass spectrum (70 eV), m / e  (relative 
intensity) 226 (100, M'), 195 (24), 167 (63), 166 (21), 165 (39), 
161 (69), 152 (15), 129 (47). 
Anal. Calcd. for C15H14O2: C, 79.62; H, 6.24. Found: C, 79.50; 
H, 5.96. 
Methyl 3-Methylbicyclo[2.2.l]hepta-2,5-diene-2- 
carboxylate (4b). 2-Butynoyl chloride (lb; from 2-butynoic acid8 
and SOC12;9 4.00 g, 39.0 mmol) and cyclopentadiene (2.70 g, 40.9 
mmol) were combined at room temperature (N2 atmosphere). 
After 48 h at  ambient temperature more cyclopentadiene (2.70 
g, 40.9 mmol) was added, and the mixture was left for another 
48 h and worked up as above. The crude material was purified 
by filtration over silica gel. After elution of dicyclopentadiene 
with petroleum ether, 4b was eluted with ether, the ether evap- 
orated, and the residue distilled: 5.0 g (78%) of 4b; bp 67-70 "C 
(4 mmHg) [lit! bp 85-90 "C (15 mmHg)]. For spectral data, see 
ref. 6. 
Methyl 3-tert-Butylbicyclo[2.2.l]hepta-2,5-diene-2- 
carboxylate (4c). 4,4-Dimethyl-2-pentynoyl chloride (IC; from 
4,4-dimethyl-2-pentynoic acidlo and SOC12;g 9.00 g, 62.2 mmol) 
and cyclopentadiene (5.00 g, 75.6 mmol) were combined at 20 "C 
(N2 atmosphere). After 30 h more cyclopentadiene (4.10 g, 62.0 
"01) was added, and the mixture was stirred for 5 days at room 
temperature and worked up as described for 4a: 10.5 g (82 %) 
of 4c; bp 62-64.5 "C (1 mmHg); IR (neat) 3070,2950,2870,1720, 
1600,1560,1480,1460,1435,1365,1300,1235,1195,1160,1090, 
1050, 725 cm-'; 'H NMR (CC14) 6 1.16 (s, 9 H), 1.88 (m, 2 H), 3.67 
(s and m, 5 H), 6.82 (m, 2 H); mass spectrum (70 eV), m / e  (relative 
intensity) 206 (58, M'), 191 (21), 175 (22), 174 (40), 159 (24), 147 
(80), 141 (51), 131 (100). 
Anal. Calcd for Cl3Hl8O2: C, 75.69; H, 8.80. Found C, 76.00, 
H, 9.05. 
Acknowledgment. We thank the Deutschen For- 
schungsgemeinschaft and the Fonds der Chemischen In- 
dustrie for support of this work. 
Registry No. la, 7299-58-3; lb, 39753-54-3; IC, 52324-03-5; 
4a, 24161-43-1; 4b, 85894-25-3; 4c, 85894-26-4; cyclopentadiene, 
542-92-7. 
(7) Bergmann, F.; Haskelberg, L. J. Am. Chem. SOC. 1941,63,2243. 
(8) Simmross, F.-M.; Weyerstahl, P. Synthesis 1981, 72. 
(9) General procedure: 'Organikum", 7th ed.; VEB Deutscher Verlag 
der Wissenschaften: Berlin, 1967; p 409. 
(10) Moreu, C.; Delange, R. Bull. SOC. Chim. 1903,29,648. 
Sulfinic Acids and Related Compounds. 14. 
Derivatives of 3-Sulfinopropanoic Acid's2 
J. Mark Hoch and Lamar Field* 
Department of Chemistry, Vanderbilt University, 
Nashville, Tennessee 37235 
Received November 16, 1982 
Sulfinate salts containing di- or trisulfide linkages have 
shown promise as antiradiation drugs.3 An attractive 
alternative to long sequential syntheses of such structures 
would be convergent syntheses in which separately syn- 
thesized sulfinic acid derivatives and di- or trisulfides 
become connected by a carboxylate ester linkage involving 
COzH on one of the synthons and OH on the other. For 
such purposes, 3-sulfinopropanoic acid (1)) as its sulfinate 
salt (2) or ester (3), is an attractive synthon both per se 
and as a model. This paper reports studies of several 
compounds related to 1: the salt 2, the diacid dichloride 
4, the diester 5, the thiolsulfonate 6, and various related 
compounds. 
H 0 2 S  (CH2 )2C02H Na 02 S (C H2 )2COzH R O ~ S ( C H ~ ) Z C  0 2 H 
1 2 3 
0 0  0 
II II II 
CIS(CH2)2CCI MeOS(CH2)pCOzMe H O ~ C ( C H ~ ) Z S O Z S ( C H Z ~ ~ C O Z H  
A reported method for oxidizing thiols to sulfinic acids, 
in which m-chlorobenzoic acid precipitates: was unsatis- 
factory with 3-mercaptopropanoic acid (7) because 1 co- 
precipitated. However, when an alkaline solution of the 
products was adjusted to pH 3, the acid 1 (pK, probably 
of -2 for S02H)' remained in solution as its salt, while 
m-chlorobenzoic acid could be extracted (pK, = 3.8,g 
sparingly soluble). The spectra of 2 obtained by evapo- 
rating the aqueous phase met expectation and showed a 
negligible amount of m-chlorobenzoic acid. Titration for 
sulfinic acid content by the method of Marvel and John- 
son, by using nitrous acid? indicated a content in the salt 
2 of -94% of sulfinate (with allowance for NaC1, which 
could not readily be separated and usually would be in- 
consequential); this titration is selective for sulfinic acids 
in the presence of sulfonic or carboxylic acids and related 
materials?b The identity of the 2 was confirmed by con- 
version to a bis(benzy1thiuronium) salt. Efforts to con- 
dense the carboxy salt 2 with bis(2-hydroxyethyl) disulfide 
have been unpromising so far because of solubility prob- 
lems,2 however, and we therefore turned to a study of the 
diacid dichloride 4. 
Douglass and Farah prepared 4 by chlorinating the 
mercapto acid 7,1° and others also have encountered no 
4 6 6 
(1) For paper 13, see Ekwarakrishnan, V.; Field, L. J. O g .  Chem. 1981, 
(2) Abstracted from part of the M.S. Thesis of J. Mark Hoch, Van- 
derbilt University, Nashville, TN, Dec 1982, which can be consulted for 
further details. 
(3) For leading citations, see ref 1, 4, and 5. 
(4) Klayman, D. L.; Copeland, E. S. In "Drug Design"; Ariens, E. J., 
Ed.; Academic Press: New York, 1975; Vol. 6, pp 81-142. 
(5) Sweeney, T. R. "A Survey of Compounds from the Antiradiation 
Drug Development Program of the US. Army Medical Research and 
Development Command"; Walter Reed Army Institute of Research 
Washington, DC, 1979; see especially pp 5,672,688,689, 769, and 770. 
(6) Filby, W. G.; Giinther, K.; Penzhorn, R. D. J.  Org. Chem. 1973,38, 
4070-4071. 
(7) Cf. Oae, S.; Kunieda, N. In 'Organic Chemistry of Sulfur"; Oae, S., 
Ed.; Plenum Press: New York, 1977; p 612. 
(8) Davis, M. M. 'Acid-Base Behavior in Aprotic Organic Solvents"; 
US .  Government Printing Office: Washington, DC, 1968; p 33. 
(9) (a) Marvel, C. S.; Johnson, R. S. J. Org. Chem. 1948,13,822-829. 
(b) Cf. also Kice, J. L.; Bowers, K. W. J. Am. Chem. SOC. 1962, 84, 
605-610. 
46, 4182-4187. 
0022-3263/83/1948-2601$01.50/0 0 1983 American Chemical Society 


Diels-Alder reactions of 2-alkynoyl chlorides with cyclopentadiene. a reinvestigation

Open Access LMU ( Ludwig-Maximilians-Univ. München)

2600 J .  Org. Chem. 1983,48, 2600-2601 in the syringe and injected into 3.00 mL of an aqueous solution containing 0.0091 N HCl and 0.017 M KCl. The temperature of the solution was maintained a t  60 “C by using a water bath, and the procedure was performed inside an enclosure containing a nitrogen atmosphere. Another aqueous solution was prepared which contained 0.02 M Tris in the free base form, and 2 X M 1. After equal volumes of these two solutions were mixed in the stopped-flow spectrophotometer, the final pH was measured as 7.50. After correction for a 0.025-mL holdup in the injection syringe, the final concentration of 2 was calculated to be 5.02 x lo4 M and that of 3 to be 5.00 X lo4 M. In all experiments, the ionic strength of the mixed solution was calculated to be 0.01 f 0.003, disregarding the contribution of the surfactant to the ionic strength. Kinetic Studies. Reactions were monitored with a Durrum Model D-130 stopped-flow spectrophotometer equipped with a Beckmann Model DU-2 monochromater and a Tektronix Model 5103N/D15 storage oscilloscope. The oscilloscope readout was photographed by using a Polaroid camera. A constant-temper- ature circulating bath maintained the temperature at 25 * 0.2 “C. The appearance of the Ells- product was followed a t  445 nm.13b All reactions were monitored with two oscilloscope time bases, one appropriate to the faster reactions and one appropriate to the slower reactions. Rate constants were calculated from the appropriate traces. First-order kinetic behavior was observed for the fastest reaction, with correlation coefficients greater than 0.999 for computer-generated correlations of log (Al- - At) with time. The fastest reaction was rapid enough so that product oxidation could be ignored. The rate of the second reaction in Scheme I was in all cases comparable to the rate of product oxidation. The relative rate constants for the second reaction were therefore calculated from the maximum product concentrations observed. The relative maximum concentration from the second step, B, was obtained by subtracting from the maximum observed concentration that amount of product that was due to the first step (1 X 10” M) and then dividing the result by the theoretical total product yield from the second step (also 1 X M). If k, is the pseudo-first-order rate constant for the second step in Scheme I and k,, is the pseudo-first-order rate constant for product oxidation, then 8, can be approximated by (k,,/k,,) raised to the power kOx/(k , ,  - The ratio between k,, and k, was then calculated for 0- in each case. On the assumption that k,, was the same in each case, the “ratio of ratios” thus gave the relative rate constants for the second step at different thiol  concentration^.^^ The estimate of k, was obtained from measurement of the time at which 8, was observed, T ,  in the experiment with 0.001 M 2. By use of the above rate constants, T- can be approximated by (l/(ko, - k,&) In (kox/k+2).22 The nature of the absorption vs. time reaction trace was such that a precise T~~ value was not obtained; nevertheless T, lay between 10 and 100 s. Using these two boundary values and the relation k,, = 0.138 k,, (from the 8, value), we calculated that 0.0032 8-l < k,, < 0.032 s-l; we thus estimate that 12, < 32 L mol-l 5-l. The occurrence of the oxidation reaction, which forces us to resort to the foregoing analysis, cannot be easily prevented. The vesicles were prepared in a nitrogen atmosphere, but oxygen is apparently introduced during the transfer of the solutions to the stopped-flow spectrophotometer. We suspect that only be en- closing that instrument in a nitrogen atmosphere, and thus performing the entire experiment under an inert atmosphere, could we completely eliminate the complication of product oxi- dation. Acknowledgment. I thank Professor Robert A. Moss for helpful discussions and Professor Jean-Marie Lehn for assistance in preparing this paper. Financial support from (22) Moore, J. W.; Pearson, R. G. “Kinetics and Mechanism”, 3rd ed.; Wiley: New York, 1981; p 290 ff. (23) It must be noted that this is a crude calculation; the relations used are exactly true only for two consecutive frat-order reactions. The system we observed involved two parallel pseudo-first-order reactions, followed by a third, consecutive pseudo-first-order reaction. There is no simple kinetic solution which can analyze completely such a system. Therefore, the initial reaction has been ignored, because it is much more rapid than the two reactions which follow. 0022-326318311948-2600$01.50/0 the National Science Foundation is also gratefully ac- knowledged. Registry No. 1, 69-78-3; 2, 79246-00-7; 3, 70755-47-4; (n- C16H33)2N+(CH3)CH2CHzSSEll, 85908-82-3. Diels-Alder Reactions of 2-Alkynoyl Chlorides with Cyclopentadiene: A Reinvestigation Englbert Biiuml and Herbert Mayr* Institut fur Organische Chemie der Friedrich- Alexander- Uniuersitat Erlangen-Nurnberg, 0-8520 Erlangen, Federal Republic of Germany Received November 16, 1982 Diels-Alder reactions of cyclopentadiene represent a simple access to the bicyclo[2.2.1] skeleton.la While electron-deficient alkenes react readily with cyclo- pentadiene,lblc cycloadditions to triple bonds appear to be problematic. While alkenoyl chlorides are among the most reactive dienophiles,’bpc phenylpropynoyl chloride has been reported “not to undergo appreciable reaction with cyclopentadiene at  room temperature even after 24 hSe2 Therefore, Baum and Viehe used a route via acetylenic iminium salts for synthesizing compounds of type 4.3 In earlier papers, however, Diels-Alder reactions of la with cyclopentadiene have been r e p ~ r t e d . ~ ~ ~  Forty-one percent of cycloadduct was obtained when a solution of la and 2 in toluene was heated at  reflux for 48 h.4 Other workers describe a spontaneous reaction of la with 2 at room temperature in the presence of a “few crystals of picric acidne5 The in- consistency of these reporta prompted us to reexamine the reactions of alkynoyl chlorides with cyclopentadiene. When la and 2 were mixed at 0 “C, warmed up to room temperature, and poured into a suspension of sodium bicarbonate in methanol, 84% of ester 4a was obtained. Combining these cycloaddends without external cooling resulted in a rapid exothermic cycloaddition reaction ac- companied by partial polymerization of cyclopentadiene. Alkynoyl chlorides lb and IC reacted with cyclopentadiene at room temperature to give good yields of norbornadienes 4b and 4c, respectively. Because of the mild reaction \ 2 COCl  COZCHJ l a ,  R = Ph b, R = CH, 3 4a, 84% c, R = C(CH,), b, 78% c, 82% conditions employed for these cycloadditions6 and the versatile reactivity of acid chlorides 3, we consider the title reaction as the method of choice for the synthesis of any ~~~ (1) (a) Sauer, J. Angew. Chem., Int. Ed.  Engl. 1966,5,211. (b) Sauer, J.; Wiest, H.; Mielert, A. 2. Naturforsch., B: Anorg. Chem., Org. Chem., Biochem., Biophys. Biol. 1962,17,203. (c) Sauer, J. Angew. Chem., Int. Ed.  Engl. 1967,6, 16. (2) Glass, R. S.; Smith, D. L. J. Org. Chem. 1974, 39, 3712. (3) Baum, J. S.; Viehe, H. G. J. Org. Chem. 1976, 41, 183. (4) Cristol, S. J.; LaLonde, R. T. J. Am. Chem. SOC. 1959,81, 5417. (5) P m ,  G. I.; Kleis, J.; Wittekind, R. R.; Rosenau, J. D. J. Org. Chem. 1961,26,4898. (6) Diels-Alder reaction of 2-butynoic acid with cyclopentadiene is carried out a t  185 OC: Simmross, F.-M.; Weyerstahl, P. Liebigs Ann. Chem. 1981, 1089. 0 1983 American Chemical Society J.  Org. Chem. 1983, 48, 2601-2603 2601 norbornadiene-2-carboxylic acid derivatives. Since even the sterically hindered tertiary butyl compound IC reacts readily a t  room temperature, this reaction should be of general applicability. Experimental Section General Procedures. Infrared spectra were recorded on a Beckman Acculab 1 IR spectrophotometer. 'H NMR spectra were taken in carbon tetrachloride on a JEOL JNM-C-60-HL spec- trometer, and mass spectra were recorded on a Varian MAT CH 4 spectrometer. Methyl 3-Phenylbicyclo[2.2.l]hepta-2,5-diene-2- carboxylate (4a). Cyclopentadiene (2.70 g, 40.9 "01) was added to precooled (0 "C) phenylpropynoyl chloride (la;' 6.00 g, 36.5 mmol) in a nitrogen atmosphere and the mixture was allowed to warm to 20 "C within 4 h. After 10 h, more cyclopentadiene (2.70 g, 40.9 mmol) was added. After the mixture was stirred for 24 h, la was consumed completely (monitoring by NMR) and the mixture was added slowly to a suspension of NaHC03 (3.5 g) in 50 mL of methanol. After 1 h, the mixture was filtered and the solvent evaporated. The residue was dissolved in 20 mL of ether and filtered, the ether evaporated, and the residue distilled: 6.93 g (84%) of 4a; bp 109-110 "C (0.2 mmHg) [lit.4 bp 111-116 "C (0.6 mmHg)]; IR (neat) 3050,2980,2940,2870, 1705, 1605,1590, 1485,1425, 1330,1290, 1230,1185, 1145,1095,1080,1070,755, 715, 690 cm-'; 'H NMR (CC14) 6 2.03, 2.23 (br AB system, J = 7 Hz, 2 H), 3.60 (s, 1 H), 3.82 (br s, 1 H), 4.03 (br s, 1 H), 6.94 (br s, 2 H), 7.1-7.7 (m, 5 H); mass spectrum (70 eV), m / e  (relative intensity) 226 (100, M'), 195 (24), 167 (63), 166 (21), 165 (39), 161 (69), 152 (15), 129 (47). Anal. Calcd. for C15H14O2: C, 79.62; H, 6.24. Found: C, 79.50; H, 5.96. Methyl 3-Methylbicyclo[2.2.l]hepta-2,5-diene-2- carboxylate (4b). 2-Butynoyl chloride (lb; from 2-butynoic acid8 and SOC12;9 4.00 g, 39.0 mmol) and cyclopentadiene (2.70 g, 40.9 mmol) were combined at room temperature (N2 atmosphere). After 48 h at  ambient temperature more cyclopentadiene (2.70 g, 40.9 mmol) was added, and the mixture was left for another 48 h and worked up as above. The crude material was purified by filtration over silica gel. After elution of dicyclopentadiene with petroleum ether, 4b was eluted with ether, the ether evap- orated, and the residue distilled: 5.0 g (78%) of 4b; bp 67-70 "C (4 mmHg) [lit! bp 85-90 "C (15 mmHg)]. For spectral data, see ref. 6. Methyl 3-tert-Butylbicyclo[2.2.l]hepta-2,5-diene-2- carboxylate (4c). 4,4-Dimethyl-2-pentynoyl chloride (IC; from 4,4-dimethyl-2-pentynoic acidlo and SOC12;g 9.00 g, 62.2 mmol) and cyclopentadiene (5.00 g, 75.6 mmol) were combined at 20 "C (N2 atmosphere). After 30 h more cyclopentadiene (4.10 g, 62.0 "01) was added, and the mixture was stirred for 5 days at room temperature and worked up as described for 4a: 10.5 g (82 %) of 4c; bp 62-64.5 "C (1 mmHg); IR (neat) 3070,2950,2870,1720, 1600,1560,1480,1460,1435,1365,1300,1235,1195,1160,1090, 1050, 725 cm-'; 'H NMR (CC14) 6 1.16 (s, 9 H), 1.88 (m, 2 H), 3.67 (s and m, 5 H), 6.82 (m, 2 H); mass spectrum (70 eV), m / e  (relative intensity) 206 (58, M'), 191 (21), 175 (22), 174 (40), 159 (24), 147 (80), 141 (51), 131 (100). Anal. Calcd for Cl3Hl8O2: C, 75.69; H, 8.80. Found C, 76.00, H, 9.05. Acknowledgment. We thank the Deutschen For- schungsgemeinschaft and the Fonds der Chemischen In- dustrie for support of this work. Registry No. la, 7299-58-3; lb, 39753-54-3; IC, 52324-03-5; 4a, 24161-43-1; 4b, 85894-25-3; 4c, 85894-26-4; cyclopentadiene, 542-92-7. (7) Bergmann, F.; Haskelberg, L. J. Am. Chem. SOC. 1941,63,2243. (8) Simmross, F.-M.; Weyerstahl, P. Synthesis 1981, 72. (9) General procedure: 'Organikum", 7th ed.; VEB Deutscher Verlag der Wissenschaften: Berlin, 1967; p 409. (10) Moreu, C.; Delange, R. Bull. SOC. Chim. 1903,29,648. Sulfinic Acids and Related Compounds. 14. Derivatives of 3-Sulfinopropanoic Acid's2 J. Mark Hoch and Lamar Field* Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235 Received November 16, 1982 Sulfinate salts containing di- or trisulfide linkages have shown promise as antiradiation drugs.3 An attractive alternative to long sequential syntheses of such structures would be convergent syntheses in which separately syn- thesized sulfinic acid derivatives and di- or trisulfides become connected by a carboxylate ester linkage involving COzH on one of the synthons and OH on the other. For such purposes, 3-sulfinopropanoic acid (1)) as its sulfinate salt (2) or ester (3), is an attractive synthon both per se and as a model. This paper reports studies of several compounds related to 1: the salt 2, the diacid dichloride 4, the diester 5, the thiolsulfonate 6, and various related compounds. H 0 2 S  (CH2 )2C02H Na 02 S (C H2 )2COzH R O ~ S ( C H ~ ) Z C  0 2 H 1 2 3 0 0  0 II II II CIS(CH2)2CCI MeOS(CH2)pCOzMe H O ~ C ( C H ~ ) Z S O Z S ( C H Z ~ ~ C O Z H  A reported method for oxidizing thiols to sulfinic acids, in which m-chlorobenzoic acid precipitates: was unsatis- factory with 3-mercaptopropanoic acid (7) because 1 co- precipitated. However, when an alkaline solution of the products was adjusted to pH 3, the acid 1 (pK, probably of -2 for S02H)' remained in solution as its salt, while m-chlorobenzoic acid could be extracted (pK, = 3.8,g sparingly soluble). The spectra of 2 obtained by evapo- rating the aqueous phase met expectation and showed a negligible amount of m-chlorobenzoic acid. Titration for sulfinic acid content by the method of Marvel and John- son, by using nitrous acid? indicated a content in the salt 2 of -94% of sulfinate (with allowance for NaC1, which could not readily be separated and usually would be in- consequential); this titration is selective for sulfinic acids in the presence of sulfonic or carboxylic acids and related materials?b The identity of the 2 was confirmed by con- version to a bis(benzy1thiuronium) salt. Efforts to con- dense the carboxy salt 2 with bis(2-hydroxyethyl) disulfide have been unpromising so far because of solubility prob- lems,2 however, and we therefore turned to a study of the diacid dichloride 4. Douglass and Farah prepared 4 by chlorinating the mercapto acid 7,1° and others also have encountered no 4 6 6 (1) For paper 13, see Ekwarakrishnan, V.; Field, L. J. O g .  Chem. 1981, (2) Abstracted from part of the M.S. Thesis of J. Mark Hoch, Van- derbilt University, Nashville, TN, Dec 1982, which can be consulted for further details. (3) For leading citations, see ref 1, 4, and 5. (4) Klayman, D. L.; Copeland, E. S. In "Drug Design"; Ariens, E. J., Ed.; Academic Press: New York, 1975; Vol. 6, pp 81-142. (5) Sweeney, T. R. "A Survey of Compounds from the Antiradiation Drug Development Program of the US. Army Medical Research and Development Command"; Walter Reed Army Institute of Research Washington, DC, 1979; see especially pp 5,672,688,689, 769, and 770. (6) Filby, W. G.; Giinther, K.; Penzhorn, R. D. J.  Org. Chem. 1973,38, 4070-4071. (7) Cf. Oae, S.; Kunieda, N. In 'Organic Chemistry of Sulfur"; Oae, S., Ed.; Plenum Press: New York, 1977; p 612. (8) Davis, M. M. 'Acid-Base Behavior in Aprotic Organic Solvents"; US .  Government Printing Office: Washington, DC, 1968; p 33. (9) (a) Marvel, C. S.; Johnson, R. S. J. Org. Chem. 1948,13,822-829. (b) Cf. also Kice, J. L.; Bowers, K. W. J. Am. Chem. SOC. 1962, 84, 605-610. 46, 4182-4187. 0022-3263/83/1948-2601$01.50/0 0 1983 American Chemical Society 

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Diels-Alder reactions of 2-alkynoyl chlorides with cyclopentadiene. a reinvestigation

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