A Convenient Synthesis of 3,4-Pentadien-1-01 from 3-Butyn-1-01 Spectral Analysis and Unusual Durability of the Allene Moiety William A. Price1 and Timothy E. Patten2 La Salk University, 20th St. and Olney Ave., Philadelphia, PA 19141 The combination of stmctural novelty with spectral and mechanistic challenge in the same undergraduate organic laboratory project is unique. The clean, one-pot preparation of the title allenic alcohol, oxidation to the corresponding carboxylic acid, and subsequent analyses of the IR and 'H NMR spectra for both compounds effectively address the above criteria. Furthermore, the exercise relies on the use of standard laboratory equipment and spectrometers (a welltuned 60-MHz NMR spectrometer is sufficient). Crabbe3 first reported that CuBr catalyzed the homologation of a variety of terminal acetylenes via treatment of the substrate with paraformaldehyde and diisopropylamine (formation of a Mannich base intermediate) in refluxing 1,4dioxane. A modification of this method allows for the clean homologation of 3-butyn-1-01 (1) to the corresponding allene, 3,4-pentadien-1-01 (2). Thus, a mixture of alkyne l, paraformaldehyde (2.5 equivalents), diisopropylamine (2.0 equiv.), and CuI (0.5 equiv.) in refluxing THF4 exclusively affords allene 2. Alternative syntheses of allenes are either multistep processes5 or are not applicable to the preparation of a P-hydroxyallene.Vhe oxidation of 2 to 3,4-pentadienoic acid (3) occurs smoothly in the presence of Jones reagent a t -10 OC in 74%. Surprisingly, under these conditions there is no isomerization of the allene system to the highly conjugated 2,4-pentadienoic acid. HCHO. CUI
H-CaCCihCwH
HNl. THF
>
CWC-CHCWIMH
2
GOl.
w*
-109
Journal of Chemical Education
Presented in part at 3rd Chemical Congress of North Americall95th National Meeting of the American Chemical Society. Toronto, Canada. June 8. 1988. Abskact #286. Corresponding author. Undergraduate Summer Research Assistant, current address: UnC versity of California at Berkeley, Berkeley, CA 94720. Searles, S.; Li. Y.; Nassim, 5.; Robert-Lopes, M.: Tran, P. T.; CrabbB. P. J. Chem. Soc. Perkin Trans. 11984, 747-751. Use of THF instead of 1,4dioxane(a cancer suspect agent)allows for gentler reaction conditions and increases the yield. Rona, P.: CrabW. P. J. Am. Chem. Soc. 1989, 91,32893292. Galantay, E.; Basco, I.; Coombs, R. V. Synthesis 1974, 344-346.
'
' CWC-CHCWIHI 3
Mechanistically, the Cu(1) immediately (and visibly) complexes with the alkyne (initially forming a chartreuse complex that gradually darkens), thereby increasing the acidity of the acetylenicproton. Undergraduates in our labs tested a
256
wide variety of Cu(I), Ag(I), Hg(I), Hg(II), and Pd(I1) catalysts (as well as the alternative bases diethylamine and di-npropylamine) and determined that CuI and CuBr with diisopropylamine were the only catalysthase combinations that gave the allene exclusively (although the reaction with CuBr gave significantly lower yields). The other catalysts either afforded mixtures of the allene and conjugated dienes, uncharacterizable products, or unreacted starting material. A logical mechanism that bas been proposed invokes a Mannich base intermediate.3 A hvdride from the aloha carbon of the amine intermediate is transferred (either directly or via CuI) toC-3 of thesubstrate. thus liberatine the homoloeated product.
60-MHz 'H NMR
sp&um of 3.4-pentadien-1-01(2).
'H NMR Analysls T h e 'H N M R spectrum of 3,4-pentadien-1-01 (2) is analyzed below:
H. b Hd \
c
oHb
,CH2CH20H
c=c=C
.+"
Hc Hd, Ht
'He
Hdt
T h e 'H below:
N M R analysis of 3,4-pentadienoic acid (3)is analyzed 0
"b \ "S. S
61.S3.8 variable (br s, 1H) 6 2.37 (m (dtdd, 2H, J b s = 6.8, Jbe = 6.6, J b d = 3.4, Jba = 3.0)) 6 3.79 (t,2H, J e b = 6.6) 6 4.81 (m (overlap-
c=c=c,
Hc
Hb*
d H.
,CH2C02H Hb, Hb, Hc Hd
6 3.12 (ddd. . . 2H. J.. = 7.0, J a b = 3.1, J a b , =
3.0)
6 4.78 (m, 2H) 6 5.26 (tdd.. 1H.. J,.- = 7.0. Jd = 7.0, Jcb. = 5.9) 6 11.52 (hr s, variable)
Several interesting features are clearly illustrated in these spectra, most notably, the nonequivalence of the terminal allenic protons for both compounds. T h e chemical shift difference-of Drotons d and d' in c o m ~ o u n d2 (and the corre~ - - sponding irotons in compound 3)-is small relative to the e x ~ e d e deeminal c o u ~ l i n econstant (-10 to -20 Hz). Thus, t h k . 4 ~pakern isdistorted to the extent that the outer peaks mav be mistaken for baseline noise. A simple first.order analysis of this portion of the spectrum would~wronglyignore any AB cou~lina.T h e unusual nine-peak multiplet a t 6 2.37 for compound (see figure) can hardly he attributed to firstorder coudinn . .either; however, due to its relative isolation, a tree diagram of t h e coupling constants given is consistent with the splitting pattern in t h e actual spectrum. Although the NMR data were obtained bv analvzinn . .ahove . - the spectra from a 300-MHz instrument, the spliitmg patterns and counline c o n s m t s can he clearlv illustrnted with a 60-MHz spectrometer (as shown in the figure). More elaborate spectroscopic studies are clearly in t h e offing (e.g., proton decoupling and H,H (and H,C) COSY experiments) for those labs with access to a high-field instrument. ~~
i
.~~~ -
Experlrnmtal W l o n Infrared spectra were obtained with a Mattson Polaris ForuierTransform Infrared Spectrophotometer. 'H NMR spectra were ohtained with a Varian T-60 or a GE QE-300 NMR Spectrometer.THF was distilled from sodiumibenzophenone prior to use. All starting materials, reagents, and solvents were obtained from Aldrieh Chemical Ca.
3.4-Pentadien- 1-01 (2) 3-Butyn-1-01 (10.02 g, 143 mmol), diisopropylamine (28.93 g, 286 mmol), and paraformaldehyde (10.74 g, 358 mmol) were added with 275 mL of dry THF to a 1-L round-bottomed flask equipped with a magnetic stirrer and a condenser fitted with a CaC12 drying tube. The mixture was stirred vigorously as the copper(1) iodide (13.62 g, 72.5 mmal) was added in small portions.' NOTE: Although the order of additionof the first three reagentsisnot critical,it ia imperatiue that the Cur be added last to eliminate any possibility of forming a copper acetylide intermediate. The reaction mixture was heated at a gentle reflux with stirring for 16 h.s The resulting brown suspension was cooled to room temperature, filtered throueh a Celite .due. .. and concentrated via rotaw. evanora. tion toa thrrk, dark Irown oil. The residue was diluced nirh 75 ml. of H O and 100 mL of ether and was then transferred to a reparatory funnel and acidified to pH 2 with 3 M HCI. The hiphssie mixture was then decanted (or filtered) from any residue, the organic phase was separawd, and the aqueous layer was wnrhed with four 5U.mL portions of ether. The combined ether layers were washed with 50 mL of H 0 rand reoeated if necessary untila pH of 7 is reached, and 100mL o f saturated NaCI. The yefiow organic solution was dried over MgS04,filtered, and carefully concentrated in vacuos (bath temperature should not exceed 35 T) to a yellow-arange ail. The crude product was then distilled under reduced pressure (short-path apparatus) to afford 4.90 g (41%isolated) of the clear, colorless allene, bp 3739'C at 4.5 mm Hg (lit.lo57-58 "Cat 16 mm Hg). The product is stable for several years if refrigerated. Infrared spertrum: 3390 (hnmd 0-H str.). 2985, I956 ( C - C - C s1r.r. 1429. 1052 (~rimarvC-O rtr.). 846 Lallenic C-H out of olane 3,4Pentadienoic Acid (3) A solution of 3,4-pentadien-1-01(2.18 g, 25.9 mmol) in 150 mL of reagent-grade acetone was placed in a 500-mL three-necked roundbottomed flaskequipped with amagneticstirrer (a mechanicalstirrer is not necessary), nitrogen inlet, and an addition funnel and cooled to -10 "C with a CaClz ice bath. The addition funnel was charged with 13 mL of Jones resgent," which was added dropwise over 45 min. After the addition was complete, the mixture was allowed to stir for an additional 90 min at -10 OC followed by removal of the ice bath and gradual warmingto room temperature. Isopropanol was added to the reddish brown mixture to destroy any excess Cr(V1). The mixture \.as filtered in vacua, and about 90%of the acetone was removed via rotary evaporation. The residual oil was diluted with 100 mL of Hz0 and extracted with three 50-mL portions of ether. The combined ether layers were dried over MgSO,, filtered, and concentrated to a yellow oil (rotaryevaporator). Distillation at reduced pressure (shortpath apparatus) gave 1.88g (74%)of the pure carboxylic acid, hp 78 'C at 2.3 mm Hg. The acid does not appear to be sensitive to light or moisture but should be refrigerated to maximize the shelf life. Infrared spectrum: 3300-2500 (broad), 1962,1724,1412,1300,856 em-'. The authors gratefully acknowledge L a Salle University and t h e National Science Foundation Grant #CS1-8750760 for partial support of this project. Also, gratitude is extended to Charles A. Stanley, Division of Endocrinology-Diabetes, Children's Hospital of Philadelphia under National Institutes of Health Grant l t P 5 0 NS 17752 for ~ a r t i aslu m o r t and for giving our work a sense of immediacy and relev&ce. 'If the Cul Is added all at once, ttm complex forms too rapldly, foaming occurs and stirring becomes difficult. Although use of 0.5 molar equivalents of Cul is sufficient, addition of up to one equivalent of catalvst does not affect the vield. h e reaction appears tdbe complete after 6 5 h, but allowing the reaction to run overnight was more convenient for our class and does not decrease the yield of the aliene. If the bath temperature exceeds 35 OC, the allene tends to codistill wim the solvent. Alternatively, the ether can be removed through a Vigreaux column under slightly reduced pressure (weak water aspirati&). 'O Bates, E. B.; Jones, E. R. H.: Whltlng, M. C. J. Chem. Soc. 1954, 1854-1859. "The Jones reagent was prepared accordlng to Fleser, M.: Fleser, L. Reagents for Organic Synthesis: Wiley-lntersclence: New Ywk, 1966; Vol. 1, p 142.
Volume 68
Number 3 March 1991
257
