[504-63-2]  · C3H8O2  · 1,3-Propanediol  · (MW 76.10)

(preparation of acetals,2,3 quinolines,4 indoles,5 boron esters;6 traps Wacker aldehyde intermediates;7 reaction solvent for Wolff-Kishner reduction8)

Alternate Name: trimethylene glycol.

Physical Data: liquid, bp 214 °C; mp -27 °C; d 1.053 g cm-3.

Solubility: sol H2O, alcohol; n sol ether; sol (hot) benzene.

Form Supplied in: >97% purity, depending on supplier.

Purification: dried with K2CO3 and distilled under reduced pressure.

Reactions with Carbonyls.

The chemistry of 1,3-propanediol (1) is dominated by acetal2,3,9,10 formation.11 Its ketone acetals show differential hydrolytic stability: cyclopentanone acetals hydrolyze faster than cyclohexanone acetals, and both hydrolyze faster than ethylene glycol-derived acetals (Table 1).3a The ketone-acetal equilibrium lies far to the left.3 Its aldehyde acetals, however, show the opposite behavior and are hydrolytically more stable than ethylene glycol acetals.3b,12 Polyketones3 and 1,4-diones13 may be selectively protected by judicious choice of substituted 1,3-propanediols. For protection of steroidal ketones, (1) is preferred over ethylene glycol, which is susceptible to attack by alkyllithium reagents.10

Conversion to Reactive Intermediates.

Acrolein condenses with (1) to give 2-(2-bromoethyl)-1,3-dioxane,2 which finds use as a three-carbon homologating agent (eq 1)14 and in the preparation of g-keto aldehydes.15 Use of (1) is essential as the corresponding ethylene glycol dioxolane is thermally unstable2 and gives Grignard reagents that tend to autodestruct.15,16 Hydrolysis of the product acetals requires special conditions.14,15

Diol (1) is used to prepare cyclopropenone acetal (2).17,18 Its highly nucleophilic double bond forms addition products with alcohols and amines17 and cycloaddition products with dienes to give norcarenes,17 ketones to give furanones and oxetanes,17 aldehydes to give butenolide, furan, and g-keto ester derivatives (eq 2),18 electrophilic alkenes to give cyclopropanes19 and functionalized cyclopentenones,20 and an a-pyrone to give a cycloheptatrienone.21

Formation of Boron Esters.

Esterification of boronic acid derivatives occurs readily with (1), and has been used in many hydroboration reaction sequences.6,22 The six-membered ring boronates are more stable than the corresponding five-membered ring or acyclic products made from 1,2-diols or alcohols. The title reagent has been used to regenerate carbohydrates from boronate derivatives.23

Heterocycle Synthesis.

Alkyl (3)24 and alkoxy (4)25 1,3,2-dioxophosphorinane 2-oxides are prepared in good yields by base-catalyzed condensation of (1) with the appropriate phosphonous dichloride. Iminosulfinyl dichlorides react similarly.26 With DCC, (1) gives 2-imino-1,3-oxazine (5) (CuCl, 95%) which is converted into urea derivatives in high yields.27

In an alternative route to the Skraup synthesis, quinolines are prepared from (1) and primary anilines (eq 3). Choice of stoichiometry, solvent, and ligand greatly affect yield.4

Regioselective synthesis of indoles is accomplished by in situ trapping of Wacker aldehydes with (1) (eq 4). o-Vinylacetanilides give indoles directly under similar reaction conditions.5 Isocoumarins and 1-isoquinolinones are also prepared by this chemistry.28 Electron-deficient alkenes give acetals with (1) under Wacker conditions (see Palladium(II) Chloride-Copper(I) Chloride).7

Miscellaneous Transformations.

1,3-Propanediol can be converted to 3-chloro-1- (60%),29 3-iodo-1- (68%),30 and 3-bromo-1-propanol (90%)31 or to 1,3-dibromopropane (85-95%).32 With imidoyl chlorides, 3-chloropropyl benzoates are produced.33 The title reagent has good solvent properties and finds use in the Wolff-Kishner reduction.8 Cyclohexenones and (1) give hydroxypropyl phenols under oxidative conditions (eq 5).34

1. (a) Cameron, D. C.; Tong, I. T.; Skraly, F. A. Prepr.-Am. Chem. Soc., Div. Pet. Chem., 1993, 38, 294. (b) Avots, A.; Glemite, G.; Dzenitis, J. Latv. PSR Zinat. Akad. Vestis, Kim. Ser. 1986, 398 (CA 1987, 106, 17 529d).
2. Stowell, J. C.; Keith, D. R.; King, B. T. OS 1984, 62, 140.
3. (a) Smith, S. W.; Newman, M. S. JACS 1968, 90, 1249. (b) Newman, M. S., Harper, R. J. JACS 1958, 80, 6350. (c) Smith, S. W.; Newman, M. S. JACS 1968, 90, 1253.
4. Tsuji, Y.; Huh, K.-T.; Watanabe, Y. JOC 1987, 52, 1673.
5. Kasahara, A.; Izumi, T.; Murakami, S.; Miyamoto, K.; Hino, T. JHC 1989, 26, 1405.
6. Brown, H. C.; Bhat, N. G.; Somayaji, V. OM 1983, 2, 1311.
7. (a) Hosokawa, T.; Ataka, Y.; Murahashi, S.-I. BCJ 1990, 63, 166. (b) Hosokawa, T.; Ohta, T.; Kanayama, S.; Murahashi, S.-I. JOC 1987, 52, 1758.
8. Campbell, T. W.; Ginsig, R.; Schmid, H. HCA 1953, 36, 1489.
9. Marton, D.; Slaviero, P.; Tagliavini, G. G 1989, 119, 359.
10. Dann, A. E.; Davis, J. B.; Nagler, M. J. JCS(P1) 1979, 158.
11. Sandler, S. R.; Karo, W. Organic Functional Group Preparations 2nd ed.; Academic: New York, 1989; Vol. 3, p 1.
12. Stowell, J. C. JOC 1976, 41, 560.
13. Cole, J. E.; Johnson, W. S.; Robins, R. A.; Walker, J. JCS 1962, 244.
14. Stowell, J. C.; Keith, D. R. S 1979, 132.
15. Stowell, J. C. JOC 1976, 41, 560.
16. Ponaras, A. A. TL 1976, 36, 3105.
17. (a) Butler, G. B.; Herring, K. H.; Lewis, P. L.; Sharpe, V. V.; Veazey, R. L. JOC 1977, 42, 679. (b) Albert, R. M.; Butler, G. B. JOC 1977, 42, 674.
18. Boger, D. L.; Brotherton, C. E.; Georg, G. I. OS 1986, 65, 32.
19. Boger, D. L.; Brotherton, C. E. TL 1984, 25, 5611.
20. Boger, D. L.; Brotherton, C. E. JACS 1984, 106, 805.
21. Boger, D. L.; Brotherton, C. E. JOC 1985, 50, 3425.
22. For alkenyl borinate transformations, see: (a) Brown, H. C.; Bhat, N. G. TL 1988, 29, 21. (b) Brown, H. C.; Imai, T.; Bhat, N. G. JOC 1986, 51, 5277. (c) Srebnik, M.; Bhat, N. G.; Brown, H. C. TL 1988, 29, 2635. (d) Brown, H. C.; Bhat, N. G.; Iyer, R. R. TL 1991, 32, 3655. For asymmetric hydroboration of prochiral alkenes, see: Brown, H. C.; Imai, T.; Desai, M. C.; Singaram, B. JACS 1985, 107, 4980.
23. Ferrier, R. J.; Prasad, D.; Rudowski, A.; Sangster, I. JCS 1964, 3330.
24. Yuan, C.; Li, S.; Cheng, Z. S 1988, 186.
25. Boisdon, M.-T.; Munoz, A.; Vives, J.-P. CR(C) 1961, 253, 1570.
26. Picard, C.; Cazaux, L.; Tisnes, P. PS 1981, 10, 35.
27. Vowinkel, E.; Gleichenhagen, P. TL 1974, 2, 143.
28. Izumi, T.; Nishimoto, Y.; Kohei, K.; Kasahara, A. JHC 1990, 27, 1419.
29. Marvel, C. S.; Calvery, H. O. OSC 1941, 1, 533.
30. Buijs, W.; van Elburg, P.; van der Gen, A. SC 1983, 13, 387.
31. Kang, S.-K.; Kim, W.-S.; Moon, B.-H. S 1985, 1161.
32. Kamm, O.; Marvel, C. S. OSC 1941, 1, 25.
33. Back, T. G.; Barton, D. H. R.; Rao, B. L. JCS(P1) 1977, 1715.
34. Horiuchi, C. A.; Fukunishi, H.; Kajita, M.; Yamaguchi, A.; Kiyomiya, H.; Kiji, S. CL 1991, 1921.

Kenneth C. Caster

Union Carbide Corporation, South Charleston, WV, USA

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