J . Org. Chem., Vol. 40, No. 21,1975
Notes Table I1 Olefinic Products from Reactions of 2-Iodobutane" with Potassium Alkoxides in Me630 a t 50" transSystem no.
9
10 11
Registry % 1-butene
2-Butene: cis-2-butene
Alkoxide
no.
Di-tert-butyl-noctadecylmethoxideb Tricyclohexylmethoxided Tri-2-norbornylmethoxided
5634830-2
24.5
5463779- 5 5634331-3
27.2
* 0.6
3.04
29.4
+ 0.5
3.41
* 0.2'
3.31
[2-BuI] = 0.1 M [ROK] = 0.25 M . Standard deviation from repetitive analysis of trapped butene mixture. [ROK] = saturated solution.
3139
prepared by dissolving the base in the appropriate solvent. Other base-solvent solutions were prepared by previously employed methods" except that KH was used instead of NaH. Procedure. For the reactions at 50°, the experimental procedure and GLC analytical techniques previously reported" were utilized. For the reactions at -2S0, a bromobenzene-liquid nitrogen slush bath was used to cool the reaction vessel and a 20-min reaction period was employed.
Acknowledgment. Acknowledgment is made to the donors of the Petroleum Research Fund, administered by the American Chemical Society, for the support of this research. Registry No.-2-Iodobutane, ide, 865-47-4.
513-48-4; potassium tert-butox-
Geferences and Notes (1) Positional orientation refers to the relative amounts of Internal and ter-
Olefinic products observed in reactions of 2-iodobutane with potassium tricyclohexylmethoxide, tri-2-norbornylmethoxide, and di-tert-butyl-n-octadecylmethoxidein MeZSO at 50' are recorded in Table 11. A nitrogen gas sweep technique1* was employed to prevent isomerization by removing butenes from the reaction vessel. For all three bases, the high trans-:cis-2-butene ratios indicate dissociated base species2 and the percentage of 1butene is higher than would be expected on the basis of estimated base strength alone.l0?l1However, only with the most ramified dissociated base, tri-2-norbornylmethoxide, does the proportion of terminal alkene approach that reported with t-BuOK-t-BuOH (Table I, system no. l), a base-solvent system in which base association plays an important Dehydrohalogenation of alkyl halides by oxyanion bases in MezSO i s very rapid.15 It might be anticipated that greater selectivity for the production of 1-butene by ramified, dissociated alkoxide ion bases might be exhibited a t lower temperatures. Reactions of 2-iodobutane with potassium tert- butoxide and tri-2-norbornylmethoxide in DMF a t -28' were therefore investigated. The results, which are presented in Table 111, reveal that, when compared with tert- butoxide, tri-2-norbornylmethoxideis even less selective in DMF at -28' than in MezSO a t 50'. Table I11 Olefinic Products from Reactions of 2-Iodobutanea with Potassium Alkoxides in DMF a t -28"
minal alkenes that are formed.
(2) R. A. Bartsch, G. M. Pruss, D. M. Cook, R. L. Buswell, B. A. Bushaw, and K. E. Wiegers, J. Am. Chem. Soc., 95, 6745 (1973). (3) S. P. Acharya and H. C. Brown, Chem. Commun., 305 (1968). (4) R. A. Bartsch, Acc. Chem. Res., 8, 239 (1975).
(5) We shall refer to contact Ion pairs and aggregates of contact ion pairs as the associated species and to free ions and separated ion pairs as the dissociated base. (6) H. C. Brown and R. L. Klimisch, J. Am. Chem. Soc., 88, 1425 (1966). (7) D. L. Griffith, D. L. Meges, and H. C. Brown, Chem. Commun.. 90 (1968). ( 8 ) Me2SO
suppresses base association owing to the strong solvation of
potassium cations by dipolar aprotic compounds. (9) R. A. Bartsch, C. F. Kelly, and G. M. Pruss, J. Org. Chem., 36, 662 (1971). (10) R. A. Bartsch, G. M. Pruss, 8. A. Bushaw, and K. E. Weigers, J. Am. Chem. SOC.,95, 3405 (1973). (11) . . R. A. Bartsch. K. E. Wieaers. and D. M. Guritz. J. Am. Chem. Soc., 96. 430 (1974). (12) H. C. Brown and M. W. Rathke, J. Am. Chem. SOC.,89, 2737 (1967). (13) H. Quast,personal communication. (14) R. A. Bartsch, J. Org. Chem., 35, 1023 (1970). (15) J. E. Hofmann, T. J. Wallace, and A. Schriesheim, J. Am. Chem. Soc., 88, 1561 (1964).
-
A Facile One-Step Synthesis of 3,5,5-Trisubstituted B(BH)-Furanones Albert Padwa" and David Dehm Department of Chemistry State University of New York a t Buffalo, Buffalo, New York 14214 Received May 20,1975
trans-
E%? 12 13
Alkoxide
% 1-butene
tert-Butoxideb 12.9 Tri-2-norb~rnylmethoxide~ 15.4
* 0.3c f
0.2d
2 -Butene: cis-2-butene
4.93 5.82
a [2-BuI] = 0.1 M . [ROK] = 0.25 M . Standard deviation from repetitive analysis of the trapped butene mixture. [ROK] = saturated solution.
In conclusion, the proportion of Hofmann orientation product which can be obtained in eliminations from 2-iodobutane induced by ramified, dissociated, tertiary alkoxide bases in MezSO is less than that reported using associated oxyanion bases. The concept of sterically hindered dissociated bases which combine the orientation control of associated bases with high reactivity therefore appears to be unworkable. Experimental Section Reagents. '4nalytical reagent grade MezSO and DMF were kept over molecular sieves. Tricyclohexylmethanol, tri-2-norbornylmethanol, and t-BuOK (Aldrich) were used directly. Di-tertbutyl-n-octadecylmethanol was provided by Dr. H. Quast, University of Wurzburg, West Germany. Base-solvent solutions of t-BuOK in MerSO and DMF were
In the course of our studies dealing with the photochemical rearrangements of a,@-unsaturatedlactones,' we required a number of 3,5,5-triaryl substituted 2(5H)-furanones. A survey of the literature revealed that there are no convenient methods to synthesize lactones of this type. An attractive route to several of the desired compounds was suggested by some recent work of Liotta2 and Durst.3 These authors showed that when the potassium salt of an acid is solubilized by complexation with crown the anionic portion becomes sufficiently nucleophilic to react smoothly and quantitatively with a wide variety of organic substrates. For example, carboxylate salts were found to undergo phase transfer reaction with a-bromoacetophenone in nonpolar solvents to give phenacyl esters by an SN2 process in quantitative yield.3 The present paper describes an application of the carboxylate displacement reaction which allows various a,a-dialkyl and diary1 acetaldehydes to be converted into 3,5,5-trisubstituted 2(5H)-furanones in high yield. Using a slight modification of the Durst procedure,3 potassium phenylacetate (1) was treated with an a-bromo substituted aldehyde (2) in the presence of 18-crown-6 to
3140
J.Org. Chem., Vol. 40, No. 21, 1975
Notes
Table I Synthesis of Trisubstituted 2(5H)-Furanones
Example
PIs.!.Ic:
1 2
R1 R1 R2 R, R, R,
3
=
Procedure
= R2 = P h ; R3 = H = P h ; R, = H
B
5 6 7
= P h : R2 = H
“c
Registry no.
B
90 81
152-1 53 139-140
3.6859-02-6 56258-94-7
A
80
120- 121
56258-95-8
A
75
112-113
56258-96-9
B
62
134-135
56258-97-0
B
20
117- 11 8
56258-98-1
80
125-1 26
7404-46-8
90
69-70
5109-73-9
= p- CH3OC gH,
R2 = H R , = R, R2 = H
8
MP,
= P-CHsOCsH,
= H;R, = P h R2 = P-CH,OC,H, R j = P h ; R3 = H R, = P-BrC,H, R , = P h ; R3 = H Rz = P-CNCsH, R, = R3 = P h
4
Yield, 9 d b
A,
B
B
CH,
a Structures were assigned on the basis of physical and spectral properties. Satisfactory analyses were obtained on all new compounds. * No attempts were made to optimize the yields.
form an aldehydo ester 3 which could be cyclized to a fivemembered unsaturated lactone 4 on further heating. We
R* I
PhCH2C02-K+ 1
+
I
R,CCHO
I
18-crown-6
Br 2
fluoride reagent produced much larger quantities of alkene products.6 The above observation confirms Liotta’s claim that “naked” fluoride is a much stronger base than ‘‘naked” acetate.*fj The mechanism for the displacement reaction on the tertiary aldehydic bromide may involve attack of solubilized acetate on a tight ion pair rather than by an s N 2 substitution path. Further work needs to be done before this point can be established.
Experimental Section
Rz 3
4
found that either acetonitrile or benzene can be used as the solvent, with the reaction proceeding faster in acetonitrile than in benzene. The reactions could be carried out by utilizing one of two different procedures. Procedure A involved heating a mixture of the appropriate a-bromo carbonyl compound with potassium phenylacetate in acetonitrile for 1hr. In this case the catalyst concentration was 0.05 M . Removal of the solvent afforded the aldehydo ester 3 (or desyl ester when desyl bromide was used) in quantitative yield. Cyclization of 3 to the desired 2(5H)-furanone system was accomplished by treating 3 with 1equiv of sodium hydride in dimethyl sulfoxide at 70° for 1-3 hr. A more convenient procedure (B) involved refluxing a mixture of 1 and 2 in benzene in the presence of 18-crown-6 (0.25 equiv) for 1-3 days. The solvent was removed under vacuum and the residue was washed with benzene through a short column (4-5 g) of dry column silica gel. Removal of the solvent afforded the desired 2(5H)-furanone(see Table I). It is interesting to note that the reaction of “naked” phenylacetate with tertiary substituted bromo aldehydes proceeds quickly and quantitatively to afford the corresponding esters in high yield. The substitution reaction occurred even when 2-bromo-2-methylpropanal was used as the substrate. Virtually no elimination product could be detected in this reaction. This result is in direct contrast to that obtained by Liotta in the reaction of “naked” fluoride with tertiary halides. His results showed that the “naked”
Synthesis of 3,5-Diphenyl-4-(p-anisyl)-2(5H)-furanone. Procedure A. To a stirred solution of 2.2 g of 4’-methoxybenzoin in 50 ml of carbon disulfide was added a solution of 1.36 g of bromine in 5 ml of carbon disulfide. After stirring for 2 hr the reaction mixture was quenched by the addition of 20 ml of a 1%aqueous sodium thiosulfate solution. The reaction mixture was washed with water and dried over sodium sulfate. Removal of the solvent gave a-bromo-4’-methoxybenzoin in quantitative yield. The crude bromo ketone was taken up in 75 ml of acetonitrile and 1.50 g of potassium phenylacetate and 132 mg of 18-crown-6 was added to the solution. The mixture was heated a t reflux for 1hr. Removal of the solvent left a yellow oil which was taken up in 100 ml of dry dimethyl sulfoxide. To this mixture was added 270 mg of sodium hydride. The reaction mixture was stirred a t room temperature for 2 hr and then warmed to 70’ for 10 min. The cooled reaction mixture was poured into cold water and extracted several times with ether. The ether layer was washed with a 2% hydrochloric acid solution and then repeatedly with water. Evaporation of the dried ethereal layer gave 3,5-diphenyl-4-(p-anisyl)-2(5H)-furanone as a white solid in 80% yield: mp 120-121O; ir (KBr) 1755 cm-I; NMR (CDC13) 6 3.62 ( ~ , H), 3 6.03 ( 8 , 1 H), 6.51 (d, 2 H, J = 8.0 Hz), 6.92 (d, 2 H, J = 8.0 Hz), 7.09-7.41 (m, 10 H); mle (70 eV) 342 (M+). Synthesis of 3,5,5-Triphenyl-2(5H))-furanone.Procedure B. To a stirred solution of 2.32 g of diphenylacetaldehyde (Aldrich) in 50 ml of carbon disulfide was added a solution of 1.35 g of bromine in 5 ml of carbon disulfide. After stirring for 1hr the reaction mixture was quenched by the addition of 20 ml of a 1%aqueous sodium thiosulfate solution. The react,ion mixture was washed with water and dried over sodium sulfate. Removal of the solvent gave a-bromodiphenylacetaldehyde in nearly quantitative yield: ir (film) 1695 cm-l; NMR (CClJ 6 9.61 (s, 1 H), 7.22 (m, 10 H). The crude bromo aldehyde was taken up in 125 ml of benzene and 1.50 g of potassium phenylacetate and 662 mg of 18-crown-6 was added t o the solution. The mixture was heated a t reflux for 24 hr with an attached Dean-Stark tube. At the end of this time the solution was concentrated under reduced pressure to 20 ml and passed through a short silica gel column with benzene to remove the crown ether.
J . Org. Chem., Vol. 40, No. 21,1975 3141
Notes 0
Evaporation of the solvent and recrystallization of the solid from methanol gave 3,5,5-triphenyl-2(5H)-furanonein 90% yield: mp 152-153'; ir (KElr) 1750 cm-'; NMR (CDC13) 6 7.98 (s, 1 H), 7.31 (m, 15 H); uv (95%ethanol) 265 and 275 nm ( e 18,200 and 16,800); mle (70 eV) 312 (M+). Anal. Calcd for C22H1602: C, 84.59; H, 5.16. Found: C, 84.28; H, 5.05.
1
2
3
4,R, = H 5,R, = Ac
Acknowledgment. Acknowledgment is made to the donors of the Pet.roleum Research Fund, administered by the American Chemical Society, for support of this research. The authors wish to thank Mr. Joel Myerson and Mr. Todd Brookhart for some experimental assistance. We also wish to thank Professor H. D. Durst for a sample of 18-crown-6 and for helpful discussions. Registry No.-1, 13005-36-2; 2 (R1 = R2 = Ph), 36930-94-6; 4'methoxybenzoin, 4254-17-5; diphenylacetaldehyde, 947-91-1.
irn"
References and Notes (1) For earlier work see A. Padwa, D. Dehm, T-Oine. and G. A. Lee, J. Am. Chem. SOC.,97, 1837 (1975); A. Padwa and 0. Dehm, J. Am. Chem. Soc., 97, 4779 (1975). (2) C. L. Liotta. H. P. Harris, M. McDermott, T. Gonzalez, and K. Smith, Tetrahedron Lett., 2417 (1974). H. D. Durst, Tetrahedron Lett., 2421 (1974). C. J. Pedersen, J. Am. Chem. SOC.,89, 7017 (1967); 92, 391 (1970); Fed. Proc., Fed. Am. SOC.Exp. Biol., 27, 1305 (1968); C. J. Pedersen and H K Frensdorff. Anaew. Chem. Int. Ed. €no/.. 84. 16 11972): J. J. Christenson, J. 0. Hili, anbR. M. Izatt, Science, l f 4 , 459 (1971). D. J. Sam and H. E. Simmons, J. Am. Chem. SOC.,94,4024 (1972) F. L Cook, C. W. Bowers, and C. L. Liotta, J. Org. Chem., 39, 3416 (1974).
C1
R," 6,R, = Ac; R, = C1 7,R, = H;R2 = C1 8, R, = H; R, = NHNH,
9, R, = C1 10, R, = NHNHCOzCHzPh
dium. Treatment of 9 with an equimolar amount of benzyl carbazate at room temperature gave a 37% yield of 10. Since it is known that the chloro group of 2,4-diamino-6chloro-5-nitropyrimidineis replaced by amines under mild condition^,^ the reaction of 9 with 2 equiv of the carbazate Preparation of 2,s-Diamino-4,6-dichloropyrimidinel was not attempted. Hydrogenation of 9 in the presence of Raney nickel gave Carroll Temple, Jr.,* Buford H. Smith, and John A. Montgomery the 5-amino compound 6. Replacement of one chloro group and removal of the %acetyl group was accomplished by Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama 35205 treatment of 6 with ethanolic hydrazine at room temperature to give 8. In some preparations of 6, this product was Received June 10,1975 contaminated with the corresponding deacetylated compound 7. Treatment of either 6 or a mixture of 6 and 7 with The projected routes for the synthesis of some condensed pyrimidine ring systems used 2,5-diamino-4,6-dichloropyri- ethanolic HCl hydrolyzed the 2-acetyl group to give 7. The reason for the considerable difference between the melting midine (7) as a key intermediate. Previously, this compoints of 7 and that previously prepared2 is unknown. The pound was obtained in two steps from 2,4,6-trichloro-5-niuse of 7 in the preparation of a pteridine has been retropyrimidine, which was prepared by the chlorodehydroxported.6 ylation of 5-nitrobarbituric acid.2 In one experiment in our laboratories, treatment of 5-nitrobarbituric acid with Experimental Section' POC13 gave a 4% yield of the desired product. In two other N-(6,7-Dihydro-2-methyl-7-oxooxazolo[ 5.4-dlpyrimidin-2experiments, the addition of N,N-dimethylaniline to the y1)acetamide (1). A mixture of 3 hemisulfate (6.0 g, 31 mmol) and POCL mixture gave a violet, exothermic reaction (inducAcnO (60 ml) was heated with stirring a t 100' for 3.5 hr. The solid tion period) resulting in the loss of the reactants. For this that deposited from the resulting solution was collected by filtrareason another route for the preparation of 7 was sought. tion and washed with EtzO: yield 3.3 g (50%);mp 294'. For analyses a portion of this sample (0.5 g) was recrystallized from H2O The chlorination of 3 with POCl3 to give 7 directly was yield, 0.3 g; mp 303'; ,A,, (e X pH 7 253 nm (15.01, 279 unsuccessful, apparently because of degradation of the ring (11.3); i,,, 1670 cm-'. system. To block the amino groups, 3 was treated with hot Anal. Calcd for CsHsN403: C, 46.16; H, 3.88; N, 26.92. Found C , AcaO, but this reaction resulted in the formation of the 46.30; H, 4.27; N, 27.39. oxooxazolopyrimidine I. Chlorination of 1 gave a mixture N-(6-Chlor0-3,4-dihydro-5-nitro-4-oxopyrimidin-2-yl)aceof products containing one to four chlorine atoms (mass tamide (5). Solid 2 (10 g, 69 mmol) was added with stirring a t 17.5' to 140 ml of of a 1:l mixture of concentrated sulfuric acidspectrum), and the investigation of this approach was ternitric acid (d 1.49-1.50). The solid dissolved in several minutes minated. and the temperature rose to 35'. After 50 min the solution was In the successful route, the 5-nitropyrimidine 43 was prepoured with stirring into crushed ice (500 9). The solid that depospared from z4 and purified by conversion to its acetylamino ited was collected by filtration, washed with water, and dried in derivative 5. Treatment of 5 with refluxing POC13 gave the vacuo over P205. The resulting crude sample of 43 was extracted dichloropyrimidine 9. In some runs this product was conwith acetone (4 X 500 ml), and the combined extract was evapotaminated with a minor impurity, presumably the correrated to dryness in vacuo. The resulting solid was suspended in acetic anhydride (100 ml) containing 2 drops of concentrated sulsponding 2-arninopyrimidine resulting from deacetylation furic acid, and the whole was heated in a preheated oil bath at 90' of 9. This impurity was reconverted to 9 by recrystallizafor 30 min. The resulting hot solution was filtered, and the filtrate tion of the sample from AczO. In one experiment, the prodwas cooled to deposit 5: yield 8.7 g; mp 260' dec (Kofler Heizuct was contaminated with 5,apparently resulting from hy(e X pH 7 242 nm (10.21, 278 sh (3.72), 356 (2.02); bank); A,, drolysis of 9 during the work-up of the acidic reaction meLax 1680 cm-'.
