Sourcebook of Advanced Organic Laboratory Preparations || ETHERS AND OXIDES

5 ETHERS

AND OXIDES

1. INTRODUCTION 2. CONDENSATION REACTIONS

A. The Williamson Synthesis 5-1. Preparation of Triphenylmethyl Ethyl Ether 5-2. Preparation of Allyl Phenyl Ether

B. Ethers and Oxides 5-3. Preparation of Isobutyl Ethyl Ether 5-4. Preparation of l-Ethoxy-2-propanol

3. OXIDATION REACTIONS A. Peroxidation of Olefins to Give Oxiranes (Epoxides)

5-5. Preparation of 1-Hexene Oxide 5-6. Preparation of Isophorone Oxide

JL-/ thers and oxides differ in the type of chemical bonding of carbon to oxygen. Oxides are three-membered rings and are attached to ad-jacent carbon atoms in a given system whereas ethers, if they are cy-clic, are not attached to adjacent carbon atoms as shown below.

From S. R. Sandler and W. Karo, Organic Functional Group Preparations, Vol. I, 2d ed. (New York, 1983), 129-146, by permission of Academic Press, Inc.

1. INTRODUCTION

34

5 ETHERS AND OXIDES 35

—C C—

Ethers

/

V. \

\ c \ —( No

/

Oxides {Epoxides)

The common methods used to produce ethers in the laboratory are the Williamson synthesis and the dehydration of alcohols using acids or inorganic oxides such as alumina.

RONa + RX ROR' + NaX

^ r. H* or Alumina Λ ΛΛ „ Λ 2 ROH > ROR + H 20

Heat 1

Ο)

(2)

Other methods involve the reaction of dialkyl sulfates with sodium alcoholates (or sodium phenolates) and the addition of olefins to alcohols or phenols using acid catalysts.

(RO)2S02 + RONa • ROR + ROSOaNa

ROH + R'CH=CH 2 RCH—CH3

I OR

(3)

(4)

The laboratory reactions with dialkyl sulfates is not preferred since it has been reported that these reagents may cause carcinogenic reactions.

Phenolic ethers can also be formed via the Claisen rearrangement as described earlier in Chapters 2 and 4 of this book.

Ethers are also formed by the base- or acid-catalyzed condensa-tion of oxides with themselves or with alcohols or phenols to give monomeric or polymeric systems.

36 5 ETHERS AND OXIDES

CH2—CH2

CH3OH

/ C H 2 - C H 2 ^

Ο Ο XC H 2— C H /

Dioxane

CH3OCH2CH2OH

Methyl cellosolve

Ethylene oxide

Base HO(CH2CH20)„—Η

Carbowax (5)

Oxides are usually formed in the laboratory by the peroxidation of olefins with H 2 0 2 , peracids, or by the dehydrohalogenation of halohydrins.

C C + B

OH x (6)

CAUTION: Ethers tend to absorb and react with oxygen from the air to form peroxides. These peroxides must be removed prior to dis-tillation or concentration to prevent an explosive detonation. In some cases, heat, shock, or friction can also cause a violent decomposition.

Some epoxides have been reported to be carcinogenic, especially those containing electron-withdrawing groups.

Due to their volatility, the lower members of the ethers and oxides are extremely flammable and care should be taken in handling these materials. Do not distill ethers to dryness.

2. CONDENSATION REACTIONS

A. THE WILLIAMSON SYNTHESIS

RX + ROH • ROR + HX (7)

The Williamson synthesis usually involves the use of the sodium salt of the alcohol and an alkyl halide. Primary halides give the best


yields since secondary and tertiary halides readily dehydrohalogenate to give olefins. However, triarylmethyl chlorides react with alcohols directly to give 97% yields of ethers [1]. Alkyl phenyl ethers are pre-pared from aqueous or alcoholic solutions of alkali phenolates and alkyl halides. Benzyl halides are easily replaced by alkoxy groups in high yields. Polar solvents such as dimethylformamide favor the re-action. Phase transfer catalysis has been reported to aid this reaction.

5-1. Preparation of Triphenylmethyl Ethyl Ether | 1 |

(C6H5)3C—CI + C 2H 5OH • (C 6H 5) 3C—OC 2H 5 + HCl (8)

To an Erlenmeyer flask containing 100 ml of absolute ethanol is added 27.9 gm (0.10 mole) of triphenylmethyl chloride. The flask is heated to get rid of hydrogen chloride. Upon cooling, 28.0 gm (97%) of the trityl ethyl ether separates, m.p. 83°C

5-2. Preparation of Allyl Phenyl Ether |2 |

C6H5OH + CH 2=CH—CH 2Br *2 C O

\ C 6H 5OCH 2—CH=CH 2 (9) Acetone

In a flask equipped with a reflux condenser are placed 18.8 gm (0.20 mole) of phenol, 24.2 gm (0.23 mole) of allyl bromide, 28.0 gm (0.20 mole) of potassium carbonate, and 200 ml of acetone. The con-tents are refluxed for 10 hr, cooled, treated with 200 ml of water, and extracted three times with 25-ml portions of ether. The combined ether extracts are washed with 10% aqueous sodium hydroxide and three times with 25-ml portions of a saturated NaCl solution, dried, and distilled to yield 22 gm (82%) of the product, bp 119.5%-120.5°C (30.2 mm), η

2

Ό

5 1.5210, v m ax 882 cm"

1.

B. ETHERS AND OXIDES

5-3. Preparation of Isobutyl Ethyl Ether [31

CH3—CH—CH2ONa + ( C 2H 5) 2S 0 4 >

CH3 I

CH3—CH—CH2OC2H5 + Na(C 2H 5)S0 4 (10)


To a flask is added 93 gm (1.25 moles) of dry isobutyl alcohol followed by 12.5 gm (0.54 gm atom) of sodium (small pieces). The exothermic reaction causes the mixture to reflux. After the reaction ceases it is heated by means of an oil bath at 120°-130°C for 2\ hr. After this time, some of the sodium still remains unreacted. The mix-ture is cooled to 105°-115°C and 77.1 gm (0.5 mole) of diethyl sulfate is added dropwise over a 2-hr period. The reaction is exothermic and steady refluxing occurs while the addition proceeds. The mixture is refluxed for 2 hr after all the diethyl sulfate has been added. The re-action mixture is cooled to room temperature. Then to it are added an equal weight of crushed ice and a slight excess of dilute sulfuric acid. The ether is steam-distilled off, separated, washed three times with 30% sulfuric acid, washed twice with water, and then dried over potassium carbonate. The dried product is refluxed over sodium ribbon and then fractionally distilled to give 35.7 gm (70%) of iso-butyl ethyl ether, bp 78°-80°C, n

2

O

s 1.3739.

Alcohols also react with epoxides to give hydroxy ethers by a trans opening of the ring.

-CH—CH3 -±> ROCH2—CH—CH3

ο OH (11)

Cyclohexene oxide reacts with refluxing methanol in the presence of a catalytic amount of sulfuric acid to give fraHs-2-methoxycyclo-hexanol in 82% yield. Unsymmetrical epoxides such as propylene oxide give a primary or secondary alcohol, depending on the reaction conditions. Base catalysis favors secondary alcohol formation where-as acid or noncatalytic conditions favor a mixture of the isomeric ethers. Epichlorohydrin can be used in a similar manner to give chlorohydroxy ethers.

5-4. Preparation of l-Ethoxy-2-propanol | 4 |

CH3—CH—CH2 + C2H5OH > CH3—CH—CH2OC2H5

Xo

7 i H (12)

To a mixture of 2560 gm (55.5 moles) of absolute ethanol and 10 gm of sodium hydroxide at 16°-ITC is added 638 gm (11 moles) of propylene oxide over a period of 4 hr. The mixture is boiled for


2 additional hr until the temperature becomes steady at 80°C. Distil-lation of the neutralized liquid yields 770 gm (81.4%) of 1-ethoxy-2-propanol, bp 130°-130.5°C.

3 . OXIDATION REACTIONS

A. PEROXIDATION OF OLEFINS TO GIVE OXIRANES (EPOXIDES) [5-8]

• CAUTION: All organic peracid reactions should be conducted be-hind a safety shield because some reactions proceed with uncontrol-lable violence. Reactions should first be run on a small scale, e.g., 0.1 mole or less, before scaling the preparation up. Efficient stirring and cooling should be provided.

Peracids and other peroxides can be destroyed by the addition of ferrous sulfate or sodium bisulfite [7].

Peracid-containing mixtures should not be distilled until the peracids have been eliminated.

The preparation of peracetic, performic, perbenzoic, and mono-perphthalate acids have been described. m-Chloroperbenzoic acid is available; it has the advantage of being more stable than perbenzoic acid. Higher aliphatic peracids have been prepared in sulfuric acid as a solvent with 50% hydrogen peroxide.

5-5. Preparation of 1-Hexene Oxide [9|

To a round-bottomed flask are added 24.4 gm (0.119 mole) of m-chloroperbenzoic acid (85% pure) and 10.0 gm (0.119 mole) of 1-hexene in 300 ml of anhydrous diglyme. The flask is then placed in the refrigerator for 24 hr and afterward the reaction mixture is sub-jected to distillation through a 2-ft helices-packed column to give 7.05 gm (60%)of 1-hexene oxide, bp 116°-119°C, «è

0 1 4051.

ο ο COOH C—OH

(13)


5-6. Preparation of Isophorone Oxide [10]

To a flask containing a stirred mixture of 55.2 gm (0.4 mole) of isophorone and 115 ml (1.2 moles) of 30% aqueous hydrogen per-oxide in 400 ml of methanol at 15°C is added 33 ml (0.2 mole) of 6 Ν aqueous sodium hydroxide over a period of 1 hr at 15°-20°C. The resulting mixture is stirred for 3 hr at 20°-25°C and then poured into 500 ml of water. The product is extracted with ether, dried over anhydrous magnesium sulfate, and distilled to yield 43.36 gm (70.4%), bp 70°-73°C (5 mm), η

2

Ό

5 1.4500-1.4510.

R E F E R E N C E S

1. A. C. Nixon and G Ε. K. Branch, / . Am. Chem. Soc. 58 ,492 (1936). 2. W. N . White and Β. E. Norcross, J. Am. Chem. Soc. 83 , 3268 (1961). 3. Ε. M. Marks , D . Lipkin, and B. Bettman, / . Am. Chem. Soc. 59, 946 (1937). 4. H. C. Chitwood and B. T. Freure, J. Am. Chem. Soc. 68, 680 (1946). 5. D . Swern, J. Am. Chem. Soc. 69, 1692 (1947). 6. D. Swern, Chem. Rev. 45 , 1 (1949). 7. D. Swern, Org. React. 7, 378 (1953). 8. E. Searles, "Preparat ion, Properties, Reactions and Uses of Organic Peracids

and Their Sal ts ." F .M.C. Corporat ion, Inorg. Chem. Div., New York, 1964; B. Phillips, "Peracetic Acid and Derivatives." 2nd ed. Union Carbide Chem-icals Co. , New York , 1957.

9. D. J. Pasto and C. C. Cumbo , J. Org. Chem. 30, 1271 (1965). 10. H. O. House and R. L. Wasson, J. Am. Chem. Soc. 79, 1488 (1957).

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Sourcebook of Advanced Organic Laboratory Preparations || ETHERS AND OXIDES