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O-Carbamates
CHAPTER
il / O-CARBAMATES
1. Introduction . . . . 2. Condensation Reactions A. Reactions of Alcohols with Urea 2-1. Preparation of Methyl Carbamate 2-2. Preparation of Ethyl Carbamate 2-3. Preparation ofn-Butyl Carbamate 2-4. Preparation of 2-Ethylbutyl Carbamate B. Reactions of Alkyl Chloroformâtes with Ammonia C. Reactions of Sodium Cyanate with Alcohols in the Presence of Acids 2-5. Preparation oft-Butyl Carbamate D. Transesterification of Carbamates 2-6. Preparation of Benzyl Carbamate 3. Miscellaneous Methods References . . . .
235 236 236 238 238 238 239 240 241 241 243 244 244 244
1. INTRODUCTION O-Carbamates represent a class of compounds distinct from those discussed in Chapter 10, which are 7V-carbamates (substituents on the nitrogen atom) O
O
II
II
ROC—NH2 (I) O-carbamate
ROC—NHR (II) N-carbamate
(structures I, II). In this chapter only carbamates with varying substituents on the oxygen atom are discussed. The recent industrial applications of carbamates as a tranquilizer [ 1 ] (structure III), a crease-resistant agent (when reacting with formaldehyde) in the textile industry [2], a solvent [3], hair conditioners [4], a plasticizer [5], and a fuel additive [6] have stimulated interest in the synthesis of various carbamates. CH3
X
CH2OCONH2
C3H7 CH2OCONH2 (III) Meprobamate, a tranquilizer 235
236
11. 0-Carbamates
The O-carbamates are usually solids; some representative examples are shown in Table I. TABLE I MELTING POINTS OF O-CARBAMATES
Carbamate
M.p. (°C)
Methyl Ethyl Λ-Propyl Isopropyl w-Butyl Lauryl «-Octyl tf-Stearyl
54.2 48.2 60 95 53 81-82 67 94-95
The most important methods of preparing (9-carbamates are shown in Eq. (1). ? O O
I
ROCNH 2
NaOCN
ROH
CF3COOH,
NH2CNH2
ROCNH2
COClz
ROH
-ROH
-
y
(1)
ROCOC1
O
II
R'NH 2
ROCNH2
f
ROCONHR'
2. CONDENSATION REACTIONS A. Reactions of Alcohols with Urea The reaction of primary alcohols with urea gives carbamates when the reac tion is carried out at 115°-150°C [7-10] (Eqs. 2, 3). Since 150°C is the tempera ture for the optimum dissociation of urea to cyanic acid and ammonia, lowerboiling alcohols (methyl, ethyl, and propyl) must be heated under pressure. Refluxing urea and w-butanol at 115°-120°C requires a 40-hr reaction time to give a 75 % yield of butyl carbamate [8].
o II NH 2 —CNH 2 HNCO + ROH
HNCO + NH 3
(2)
RO—CNH 2
(3)
O
237
§ 2. Condensation Reactions
In order to shorten the reaction time, various heavy metal salts (zinc, lead, and manganese acetates) of weak organic acids, zinc or cobalt and tin chlorides are added to the reaction mixture [11]. For example, refluxing an uncatalyzed mixture of 3 moles of isobutyl alcohol and urea for 150 hr at 108°-126°C gives a 49 % yield of the carbamate. Adding lead acetate or cobalt chloride to the same reaction lowers the reaction time to 75 hr, at which point an 88-92 % yield is obtained. In another example, ethylene glycol (1 mole) and urea (2 moles) are heated for 3 hr at 135°-155°C with Mn(OAc)2 to give a 78% yield of the diurethane [11]. The commercial production of butyl carbamate uses catalytic quantities of cupric acetate [12]. The effects of catalysts on the yields and rates of formation of carbamates from alcohols and urea are shown in Table II. The catalytic effectiveness of BF3 has also been reported [13]. Apparently a systematic study has not been made to evaluate the compara tive effectiveness of various metals as catalysts for the reaction of urea with TABLE II e CATALYTIC EFFECT ON THE YIELDS AND RATES OF FORMATION OF CARBAMATES FROM ALCOHOLS AND UREA
Reactants Urea (moles)
Alcohol (moles)
Catalyst
(gm)
Temp. (°C)
Carbamate (yield %)
5 8 8 5 5 5
175-185 150-160 150-160 175-185 175-185 175-185
56 87 92 0 0 0
150 75 75 12 10
108-126 108-126 108-126 80-85 70-75
49 88 92 0 0
4 6 5 5
160-205 150-160 100-105 160-185
18 56 83 0
Time (hr)
Benzyl alcohol 1.0 1.0 1.0 1.0 1.0 1.0
3.0 2.0 2.0 2.0 2.0 2.0 Isobutyl alcohol
O Zn(OAc) 2 SnCl 4 cone. H 2 S 0 4 NH4HSO4 Glycerin
—
1.0 1.0 1.0 1.0 1.0
3.0 3.0 3.0 1.95 1.95 Methylcyclohexanone
O Pb(OAc) 2 COCl 2 85%H3P04 HC1 gas
—
1.0 1.0 1.0 1.0
3.02 3.02 3.02 3.02
O O Zn(OAc) 2 85%H3P04
— —
a
Data taken from Paquin [11].
4 4 1 6 8
6 5 5
7 7
238
11. Ö-Carbamates
alcohols to give carbamates. The reaction of urea with tertiary alcohols and phenols fails to give carbamates. In concentrated sulfuric acid at 20°-25°C tertiary alcohols alkylate urea in 31-33 % yields [14,15]. For the preparation of tertiary alkyl, secondary alkyl, and phenolic carbamates see Section C. 2-1. Preparation of Methyl Carbamate [12] O ||
N H 2 C N H 2 + CH 3 OH
O Cu(OAc)2 i3Q0C
>
||
CH3OCNH2 + NH3
(4)
To a flask are added 60 gm (1.0 mole) of urea, 4.0 gm (0.022 mole) of cupric acetate, and 0.5 ml of methanol. The mixture is heated to 130°C, and methanol is then added dropwise over a 3 hr period while ammonia is evolved completely. The residue in the flask weighs 31.1 gm (41 %) and has a melting point of 54°C. Ethyl, butyl, and 2-methoxyethyl carbamates are prepared similarly. 2-2. Preparation of Ethyl Carbamate [13] O Il C 2 H 5 OH + N H 2 C N H 2
BF3 >
O II C2H5OCNH2 + NH3
(5)
To a tared flask containing 600.6 gm (10 moles) of urea dissolved in 2073.2 gm of ethanol at 70°C is added, via a gas addition tube, boron trifluoride until 678.2 gm (4.3 moles) is absorbed. The ethanol is removed by distillation until the pot temperature reaches 100°C, then the reaction mixture is filtered. The solids, which consist of BF 3 -NH 3 complex, are washed with ethanol and then the ethanol is added to the original filtrate. The ethanol is then distilled off again as above and filtered again to give more BF 3 -NH 3 solids. The total BF 3 -NH 3 solids weigh 535 gm. This solid is washed with hot ethanol and the total alcohol washing and remaining ethanol filtrates cooled to give 255 gm of BF 3 -4(NH 2 CONH 2 ) complex, m.p. 96°-98°C. The combined filtrates are freed of alcohol by distillation, extracted with benzene, and the extract on distillation under reduced pressure affords 380 gm (99%) of C 2 H 5 OCONH 2 , b.p. 115°C (100 mm), m.p. 48°-50°C. The tacky residue weighs 150gm. 2-3. Preparation ofn-Butyl Carbamate [8] O NH2CNH2 + AZ-C4H9OH
O ► «-C4H9OCNH2 + NH3
(6)
§ 2. Condensation Reactions
239
To a flask in a hood is added 970 gm (13.1 moles) of w-butanol. The nbutanol is stirred and warmed to 100°C while urea ( 180 gm, 3 moles) is added in small portions. The reaction is exothermic, and the temperature is maintained below the melting point of urea so that the urea dissolves and does not settle as a molten layer. The solution is refluxed for 30 hr while ammonia escapes from the top of the condenser. The reaction mixture is distilled until the temperature reaches 150°C. On cooling, the residue solidifies and is then boiled with 1 liter of ligroin (b.p. 60°-90°C). The mixture is filtered. The remaining solids are refluxed with ligroin and then filtered. Approximately 12-18 gm (9-14%) of almost pure cyanuric acid is obtained from the ligroin-insoluble material. Dis tillation of the combined dry ligroin filtrate up to 150°C affords a residue which on distillation at reduced pressure gives 266 gm (76%), b.p. 108°-109°C (14 mm), m.p. 53°-54°C. 2-4. Preparation of 2-Ethylbutyl Carbamate [19] C2H5 CH3CH2CHCH2OH + COCl2
C2H5 >
CH3CH2CHCH2OCOCl
NHa
>
Ç2H5 CH3CH2CHCH2OCONH2
(7)
To a flask situated in a well-ventilated hood is added 1 liter of toluene. The toluene is cooled to 5°C with an ice bath and then phosgene is passed into it until 200 gm (2.0 mole) has been absorbed. To this phosgene solution is added 182 gm (1.8 mole) of 2-ethyl-l-butanol with rapid stirring. The reaction is exothermic and the temperature rises to 35°C while hydrogen chloride and some phosgene are evolved and passed through a potassium hydroxide trap. The reaction mixture is stirred for an additional 18 hr, then a dry nitrogen stream is passed through the solution for 1 hr in order to remove excess phos gene. The solution is poured, with rapid stirring, into 400 ml of concentrated aqueous ammonia, cooled to 5°C. The toluene layer is separated, concentrated under reduced pressure, and cooled in an ice bath to precipitate 195 gm (75 %), m.p. 81°C (corr.) of 2-ethylbutyl carbamate. Other carbamates such as ethyl-«-propyl, isopropyl, 3-butyl, isobutyl, secbutyl, fl-amyl, isoamyl, 2-methylbutyl, 1-ethylpropyl, and 2-ethylhexyl carb amate were prepared in a manner similar to that described here for 2-ethylbutyl carbamate in 55-76% yields [19]. Benzyl carbamate has also been reported to be prepared by this method in 91-94% yield [17]. Table III gives the preparation of several chloroformâtes and their con version into carbamates using aqueous ammonia.
240
11. 0-Carbamates TABLE IIIfl PREPARATION OF CHLOROFORMÂTES A N D CONVERSION
INTO
CARBAMATES USING AQUEOUS AMMONIA
ROCH2CH2OH + COCI2 -> ROCH2CH2OCOCl B.p., °C (mmHg)
ROCH2CH2OCOCI + NH 3 -+ ROCH2CH2OCONH2
R
Yield (%)
M.p. (°C)
CH 3 C2H5 CH3(CH2)3
93 77 91
58.7(13) 67.2(14) 93.0-93.5(14)
1.4163(25) 1.4169(25) 1.4241(25)
(C6H5)2CH
72
87.0-87.5(8.5)
1.4261(25)
nj
B.p., °C (mm Hg)
nj
46.8 — 62.2 — — 132.2-132.4 (2.5) — 133-134(2.5)
Yield (%)
— — —
13.3 39.0 63.5
—
63.5
"Data taken from Porai-Koshits and Remizov [16].
B. Reactions of Alkyl Chloroformâtes with Ammonia The ammonolysis of alkyl chloroformâtes affords an excellent laboratory method for the preparation of carbamates [16-20]. However, since phosgene is involved in the preparation of the chloroformate ester, great caution must be exercised. It is mandatory that phosgene be used in a well-ventilated hood. Where possible, the urea-alcohol method of Section A should be used because of the more favorable weight relationship of urea compared to phosgene. Assuming 100% reaction, the weight relationships given in Eqs. (8), (9), and (10) would hold. Section B : CH3OH + COCl2 32 gm
99 gm
CH3OCOCI + 2NH3 94.5 gm
34 gm
>
CH3OCOCI + HCI
(8)
94.5 gm 36.5 gm ► CH3OCONH2 + NH4CI 75 gm
(9)
53.5 gm
Section A : CH3OH + NH2CONH2 32 gm
60 gm
► CH3OCONH2 + NH 3 75 gm
(10)
17 gm
It should be noted that the method of Section A gives ammonia by-product which can be used to prepare more urea. However, Section B gives ammonium chloride, which requires costly conversion into free ammonia.
241
§ 2. Condensation Reactions
C. Reactions of Sodium Cyanate with Alcohols in the Presence of Acids Werner [21] reported that ethanol reacted with an aqueous solution of sodium cyanate and hydrochloric acid to give a 56 % yield of ethyl carbamate. Similar results were obtained with potassium cyanate [22, 23]. Tertiary alco hols were reported earlier to react with potassium cyanate in acetic acid to give dehydration or rearrangement but no carbamate [24]. Marshall [25] and others [26,27] described a method whereby tertiary alcohols reacting in situ generated cyanic acid from a mixture of anhydrous sodium cyanate in trichloroacetic acid. Loev [28] recently reported that modifying Marshall's procedure by using trifluoroacetic acid affords ί-butyl carbamates in over 90% yields. The beneficial effect of trifluoroacetic acid does not appear to be solely related to increased acid strength as hydrochloric acid or methanesulfonic acid gives only traces of carbamate when used in place of trifluoroacetic acid under similar conditions. The role of trifluoroacetic acid in the mechanism of this reaction requires further investigation. When the reaction is run in benzene and méthylène chloride, better yields are obtained than from similar reactions run in ether, tetrahydrofuran, or carbon tetrachloride. Surprisingly it was reported that when potassium cyanate is substituted for sodium cyanate the yields of carbamates are reduced to less than 5 %. The reason for this drastic effect is not known at this time. In addition, the use of other alkali or alkaline metal cyanates in this reaction has not been investi gated. The Loev [28] procedure appears applicable to the synthesis of carb amates from primary, secondary, and tertiary alcohols (2 hr reaction time affords 60-90% yields), cyclic and acyclic 1,3-diols, phenols, oximes, aldoximes, and ketoximes, and primary, secondary, and tertiary mercaptans. Carbamates could not be obtained from diphenylethylcarbinol (dehydrated to 1,1-diphenylethylene) or trichloro- and trifluoromethylcarbinols. Although earlier investigators [24, 29, 30] reported that cyanic acid reacts with alcohols to give allophonates, Loev [28] never detected any of these in his procedure. The only by-product was trifluoroacetamide, which did not present a difficulty because of its high solubility in water and organic solvents. Table IV illustrates the production of carbamates by the reaction of sodium cyanate and alcohols in the presence of trifluoroacetic acid. .2-5. Preparation oft-Butyl Carbamate [28] CH 3 CH 3 —C—OH + NaOCN CH 3
CAUTION: Use a hood.
CF3C00H _ H ► <-6 6
CH 3 O I II CH3-C-OCNH2 I
CH
,^x (11)
0.21
0.21
0.21
i-BuSH
Me | Et 2 C—SH
/ 0.20
0.20
100
0.20
100
100
CH2C12
100
100
100
100
Ether
0.20
0.20
0.20
D a t a taken from L o e v and K o r m e n d y [28].
\=NOH
0.21
«-BuSH
OH
1
Me2^/jy-Me2
T
0.21
0.21
C 6 H 5 OH
OH
0.21
CH=C—CH 2 OH
18
18
4
3
18
48
3
2
0.20
2
100 100
0.20
0.21
t-BuOH
CÓHÓ
0.20
0.21
Time (hr)
rt-BuOH
Solvent (ml)
NaOCN (moles)
CF3COOH (moles)
Alcohol
a
T A B L E IV a
30
30
30
30
30
30
30
30
30
Temp. (°Q
\=NOCONH2
Me | Et 2 C—SCONH 2
/-BuSCONH 2
K-BuSCONH2
/
2
OCONH 2
1
Me2-^N-Me
OCONH 2
C 6 H 5 OCONH 2
90
25
50
65
45
62
60
92
CH=C—CH 2 OCONH 2
73
A*-BUOCONH2
Yield (%)
r-BuOCONH 2
Product carbamate
94-96
45-47
92-95
98-100
175-185
145-148
H20
Hexane
Hexane
Hexane
H20
H20
Benzene
Hexane 47-50
H20 53-54
Recryst. solvent
107-108
M.p. (°C)
SYNTHESIS OF CARBAMATES VIA THE R E A C T I O N OF S O D I U M C Y ANATE A N D A L C O H O L S I N THE PRESENCE OF TRIFLUOROACETIC A C I D
243
§ 2. Condensation Reactions
To a stirred mixture of 7.4 gm (0.1 mole) of /-butyl alcohol and 13.0 gm (0.2 mole) of sodium cyanate in 50 ml of benzene is slowly added 15.5 ml (0.21 mole) of trifluoroacetic acid. The reaction is exothermic and some gas bubbles are formed. The reaction is stirred for 3 hr, then 15 ml of water is added, the organic layer separated, dried, the solvent removed under reduced pressure at a pot temperature of 40°-50°C ; the resulting residue solidifies to afford 10.7 gm (92%), m.p. 98°-10rC. Recrystallization of the entire product from water affords 8 gm (69%), m.p. 107°-108°C. D. Transesterification of Carbamates Carbamates have been prepared by heating ethyl carbamate with a higherboiling alcohol in the presence or absence of catalysts [31-33]. Aluminum isopropoxide has been reported [34] to be an excellent catalyst for the interchange reaction between ethyl carbamate and benzyl alcohol. The interchange reac tion is also effective for N-alkyl carbamates as well as unsubstituted carb amates [35]. This catalyst is effective in preparing mono- and dicarbamates in excellent yields from primary and secondary alcohols and diols. Other effec tive catalysts are: dibutyltin dilaurate [36], dibutyltin oxide [37], sulfuric acid or/7-toluenesulfonic acid [31], and sodium metal (reacts with alcohols to give the alkoxide catalyst) [33]. Examples of the transesterification reaction of ethyl carbamates and alco hols are given in Table V. TABLE \Ta TRANSESTERIFICATION REACTION OF ETHYL CARBAMATES AND ALCOHOLS
Alcohol Isobutyl
sec-Butyl /-Butyl Benzyl
a
Mole ratio of ethyl carbamate/ alcohol Catalyst 1/6 1/6 1/6 1/6 1/6 1/1.5 1/1.5 l/lc
O H2S04e (fl-Bu) 3 N
H2S04 H2SO4
O H2SO4
Al (iso-PrO) 3
Temp. (°C)
Time (hr)
Yield (%)
110-120 110-120 110-120 105-110 85-90 190-230 145-240 130-140 d
103 19 8 16
— 87 (56)& — 37
—
19 5 5-10
—
70 (53)b 9 86
Data taken from Gaylord and Sroog [31] except where noted. Recrystallized product. c Data from Kraft [34]. d Bath temperature. e Approximately 2 ml concentrated H2SO4/0.5 mole ethyl carbamate used. b
M.p. (°Q
— 63-64
—
92-93
—
85-86 82-84 86-87
244
11. 0-Carbamates
Tertiary alcohols and phenols do not undergo the transesterification reaction of carbamates with acidic or basic catalysts [38]. 2-6. Preparation of Benzyl Carbamate [34] O II
C2H5OCNH2 + C6H5CH2OH
Al(iso-PrO) 3
-+
O 'I
C6H5CH2OCNH2 + C2H5OH
,
(12)
To a 250 ml three-necked flask equipped with a thermometer and a 20 cm distillation column filled with glass beads are added 44.5 gm (0.5 mole) of ethyl carbamate, 54.1 gm (0.5 mole) of benzyl alcohol, and 60 ml of toluene. The reaction flask is heated with an oil bath at 110°-125°C in order to remove any water in the reagents. The bath is cooled to 100°C, and 2.0 gm (0.01 mole) of aluminum isopropoxide is added all at once. The reaction is heated with the oil bath set at 130°-140°C in order to remove about 50 ml of the ethanoltoluene azeotrope at 77°C. The residue is recrystallized from toluene to yield 64.5 gm (85.5%), m.p. 86°-87°C. NOTE: Substituting sodium methoxide for aluminum isopropoxide gave poor yields. 3. MISCELLANEOUS METHODS (1) Ammonolysis of diethyl carbonate to ethyl carbamate [39]. (2) Preparation of tertiary alkyl esters of carbamic acid by the ammono lysis of mixed phenyl alkyl carbonates to yield alkyl carbamate and phenol [24, 40, 41]. (3) Reaction of urea and ethylene oxide to give aminoethyl carbamates [42]. (4) Reaction of carbamoyl chloride (NH 2 COCl) with alcohols to yield carbamates [43]. (5) Reaction of alkyl oxamates with bromine and sodium ethoxide [44]. (6) Reaction of silver carbamate with alkyl halides [45]. (7) Hydrolysis of cyanates [46]. (8) Reaction of polyvinyl alcohol with urea to give polyvinyl carbamates [11,47,48]. REFERENCES
1. F. M. Berger and B. J. Ludwig, U.S. Pat. 3,724,720 (1956). 2. R. L. Arcenaux, J. G. Frick, H. O. Reid, and G. A. Gantreaux, Amer. Dyest. Rep. 50, 37 (1961). 3. Berkeley Chemical Corp., Liquithane, Bulletin, 1960. 4. I. H. Updegraff and A. Contras, U.S. Pat. 2,937,966 (1960). 5. R. T. Pollock, U.S. Pat. 2,438,452 (1948).
References 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48.
245
P. Kirby and T. Owen, Brit. Pat. 961,569 (1964). R. A. Jacobson, / . Amer. Chem. Soc. 60, 1742 (1938). T. L. Davis and S. C. Lane, Org. Syn. Coll. Vol. 1, 140 (1941). A. E. A. Werner, /. Chem. Soc. 113, 622 (1918). F. M. Meigs, U.S. Pat. 2,197,479 (1940). M. Paquin, Z. Naturforsch. 1, 518 (1946). S. Beinfest, P. Adams, and J. Halpern, U.S. Pat. 2,837,561 (1958). F.. J. Sowa, U.S. Pat. 2,834,799 (1958). L. I. Smith and O. H. Emerson, Org. Syn. Coll. Vol. 3, 151 (1955). M. T. Harvey and S. Caplan, U.S. Pat. 2,247,495 (1941). H. G. Ashburn, A. R. Collett, and C. L. Lazzell, /. Amer. Chem. Soc. 60, 2933 (1938). H. E. Carter, R. L. Frank and H. W. Johnston, Org. Syn. Coll. Vol. 3, 167 (1955). G. A. Kirkhgof and R. Y. Astrova, Khim. Farm. Prom. 282 (1933). W. M. Kraft and R. M. Herbst, J. Org. Chem. 10, 483 (1945). J. Thiele and F. Dent, Ann. Chem. 302, 246 (1898). E. A. Werner, Sci. Proc. Roy. Dublin Soc. 24, 209 (1947). O. Folin, Amer. Chem. J. 19, 336 (1897). J. H. Barnes, M. V. A. Chapman, P. A. McRea, P. G. Marshall, and P. A. Walsh, / . Pharm. Pharmacol. 13, 39 (1961). W. M. McLamore, S. Y. P'An, and A. Bavley, / . Org. Chem. 20, 1379 (1955). P. G. Marshall, J. H. Barnes, and P. A. McCrea, U.S. Pat. 2,814,637 (1957). W. Stuehmer and S. Funke, U.S. Pat. 2,878,158 (1959). J. H. Barnes, /. Pharm. Pharmacol. 13, 39 (1961). B. Loev and M. F. Kormendy, / . Org. Chem. 28, 3421 (1963). W. J. Close and M. A. Spielman, /. Amer. Chem. Soc. 75, 4055 (1953). K. W. Blohm and E. I. Becker, Chem. Rev. 51, 471 (1952). N. G. Gaylord and C. C. Sroog, /. Org. Chem. 18, 1632 (1953). G. Heilner, Ger. Pat. 551,777 (1932). M. Metayer, Bull. Soc. Chim. Fr. 802 (1951). W. M. Kraft, /. Amer. Chem. Soc. 70, 3569 (1948). R. Hazard, J. Cheymal, P. Charbrier, A. Skera, and E. Echefralaire, Bull. Soc. Chim. Fr. 2087 (1961). W. Kern, K. J. Ranterkus, W. Weber, and W. Herz, Makromol. Chem. 57, 241 (1962). P. Adams and F. A. Baron, Chem. Rev. 65, 570 (1965). N. G. Gaylord, / . Org. Chem. 25, 1874 (1960). A. Cahours, Ann. Chem. 56, 266 (1845). K. Hafner and W. Kaiser, Tetrahedron Lett. 32, 2185 (1964). Société des Laboratoires Labaz, Brit. Pat. 802,557 (1959). W. F. Touisignant and T. Houtmann, Jr., U.S. Pat. 2,842,523 (1958). L. Gatterman, Ann. Chem. 244, 29 (1888). J. Miliotis, Prakt. Akad. Athenon 10, 190 (1935). U. Iwase, Japan. Pat. 17,655 (1963). D. Martin, Angew. Chem. 76, 303 (1964). I. Sakurada, A. Nakajima, and K. Shibatani, /. Polym. Sci. A 2, 3545 (1964). F. Masuo and T. Watanabe, Japan. Pat. 13,886 (1960).
il / O-CARBAMATES
1. Introduction . . . . 2. Condensation Reactions A. Reactions of Alcohols with Urea 2-1. Preparation of Methyl Carbamate 2-2. Preparation of Ethyl Carbamate 2-3. Preparation ofn-Butyl Carbamate 2-4. Preparation of 2-Ethylbutyl Carbamate B. Reactions of Alkyl Chloroformâtes with Ammonia C. Reactions of Sodium Cyanate with Alcohols in the Presence of Acids 2-5. Preparation oft-Butyl Carbamate D. Transesterification of Carbamates 2-6. Preparation of Benzyl Carbamate 3. Miscellaneous Methods References . . . .
235 236 236 238 238 238 239 240 241 241 243 244 244 244
1. INTRODUCTION O-Carbamates represent a class of compounds distinct from those discussed in Chapter 10, which are 7V-carbamates (substituents on the nitrogen atom) O
O
II
II
ROC—NH2 (I) O-carbamate
ROC—NHR (II) N-carbamate
(structures I, II). In this chapter only carbamates with varying substituents on the oxygen atom are discussed. The recent industrial applications of carbamates as a tranquilizer [ 1 ] (structure III), a crease-resistant agent (when reacting with formaldehyde) in the textile industry [2], a solvent [3], hair conditioners [4], a plasticizer [5], and a fuel additive [6] have stimulated interest in the synthesis of various carbamates. CH3
X
CH2OCONH2
C3H7 CH2OCONH2 (III) Meprobamate, a tranquilizer 235
236
11. 0-Carbamates
The O-carbamates are usually solids; some representative examples are shown in Table I. TABLE I MELTING POINTS OF O-CARBAMATES
Carbamate
M.p. (°C)
Methyl Ethyl Λ-Propyl Isopropyl w-Butyl Lauryl «-Octyl tf-Stearyl
54.2 48.2 60 95 53 81-82 67 94-95
The most important methods of preparing (9-carbamates are shown in Eq. (1). ? O O
I
ROCNH 2
NaOCN
ROH
CF3COOH,
NH2CNH2
ROCNH2
COClz
ROH
-ROH
-
y
(1)
ROCOC1
O
II
R'NH 2
ROCNH2
f
ROCONHR'
2. CONDENSATION REACTIONS A. Reactions of Alcohols with Urea The reaction of primary alcohols with urea gives carbamates when the reac tion is carried out at 115°-150°C [7-10] (Eqs. 2, 3). Since 150°C is the tempera ture for the optimum dissociation of urea to cyanic acid and ammonia, lowerboiling alcohols (methyl, ethyl, and propyl) must be heated under pressure. Refluxing urea and w-butanol at 115°-120°C requires a 40-hr reaction time to give a 75 % yield of butyl carbamate [8].
o II NH 2 —CNH 2 HNCO + ROH
HNCO + NH 3
(2)
RO—CNH 2
(3)
O
237
§ 2. Condensation Reactions
In order to shorten the reaction time, various heavy metal salts (zinc, lead, and manganese acetates) of weak organic acids, zinc or cobalt and tin chlorides are added to the reaction mixture [11]. For example, refluxing an uncatalyzed mixture of 3 moles of isobutyl alcohol and urea for 150 hr at 108°-126°C gives a 49 % yield of the carbamate. Adding lead acetate or cobalt chloride to the same reaction lowers the reaction time to 75 hr, at which point an 88-92 % yield is obtained. In another example, ethylene glycol (1 mole) and urea (2 moles) are heated for 3 hr at 135°-155°C with Mn(OAc)2 to give a 78% yield of the diurethane [11]. The commercial production of butyl carbamate uses catalytic quantities of cupric acetate [12]. The effects of catalysts on the yields and rates of formation of carbamates from alcohols and urea are shown in Table II. The catalytic effectiveness of BF3 has also been reported [13]. Apparently a systematic study has not been made to evaluate the compara tive effectiveness of various metals as catalysts for the reaction of urea with TABLE II e CATALYTIC EFFECT ON THE YIELDS AND RATES OF FORMATION OF CARBAMATES FROM ALCOHOLS AND UREA
Reactants Urea (moles)
Alcohol (moles)
Catalyst
(gm)
Temp. (°C)
Carbamate (yield %)
5 8 8 5 5 5
175-185 150-160 150-160 175-185 175-185 175-185
56 87 92 0 0 0
150 75 75 12 10
108-126 108-126 108-126 80-85 70-75
49 88 92 0 0
4 6 5 5
160-205 150-160 100-105 160-185
18 56 83 0
Time (hr)
Benzyl alcohol 1.0 1.0 1.0 1.0 1.0 1.0
3.0 2.0 2.0 2.0 2.0 2.0 Isobutyl alcohol
O Zn(OAc) 2 SnCl 4 cone. H 2 S 0 4 NH4HSO4 Glycerin
—
1.0 1.0 1.0 1.0 1.0
3.0 3.0 3.0 1.95 1.95 Methylcyclohexanone
O Pb(OAc) 2 COCl 2 85%H3P04 HC1 gas
—
1.0 1.0 1.0 1.0
3.02 3.02 3.02 3.02
O O Zn(OAc) 2 85%H3P04
— —
a
Data taken from Paquin [11].
4 4 1 6 8
6 5 5
7 7
238
11. Ö-Carbamates
alcohols to give carbamates. The reaction of urea with tertiary alcohols and phenols fails to give carbamates. In concentrated sulfuric acid at 20°-25°C tertiary alcohols alkylate urea in 31-33 % yields [14,15]. For the preparation of tertiary alkyl, secondary alkyl, and phenolic carbamates see Section C. 2-1. Preparation of Methyl Carbamate [12] O ||
N H 2 C N H 2 + CH 3 OH
O Cu(OAc)2 i3Q0C
>
||
CH3OCNH2 + NH3
(4)
To a flask are added 60 gm (1.0 mole) of urea, 4.0 gm (0.022 mole) of cupric acetate, and 0.5 ml of methanol. The mixture is heated to 130°C, and methanol is then added dropwise over a 3 hr period while ammonia is evolved completely. The residue in the flask weighs 31.1 gm (41 %) and has a melting point of 54°C. Ethyl, butyl, and 2-methoxyethyl carbamates are prepared similarly. 2-2. Preparation of Ethyl Carbamate [13] O Il C 2 H 5 OH + N H 2 C N H 2
BF3 >
O II C2H5OCNH2 + NH3
(5)
To a tared flask containing 600.6 gm (10 moles) of urea dissolved in 2073.2 gm of ethanol at 70°C is added, via a gas addition tube, boron trifluoride until 678.2 gm (4.3 moles) is absorbed. The ethanol is removed by distillation until the pot temperature reaches 100°C, then the reaction mixture is filtered. The solids, which consist of BF 3 -NH 3 complex, are washed with ethanol and then the ethanol is added to the original filtrate. The ethanol is then distilled off again as above and filtered again to give more BF 3 -NH 3 solids. The total BF 3 -NH 3 solids weigh 535 gm. This solid is washed with hot ethanol and the total alcohol washing and remaining ethanol filtrates cooled to give 255 gm of BF 3 -4(NH 2 CONH 2 ) complex, m.p. 96°-98°C. The combined filtrates are freed of alcohol by distillation, extracted with benzene, and the extract on distillation under reduced pressure affords 380 gm (99%) of C 2 H 5 OCONH 2 , b.p. 115°C (100 mm), m.p. 48°-50°C. The tacky residue weighs 150gm. 2-3. Preparation ofn-Butyl Carbamate [8] O NH2CNH2 + AZ-C4H9OH
O ► «-C4H9OCNH2 + NH3
(6)
§ 2. Condensation Reactions
239
To a flask in a hood is added 970 gm (13.1 moles) of w-butanol. The nbutanol is stirred and warmed to 100°C while urea ( 180 gm, 3 moles) is added in small portions. The reaction is exothermic, and the temperature is maintained below the melting point of urea so that the urea dissolves and does not settle as a molten layer. The solution is refluxed for 30 hr while ammonia escapes from the top of the condenser. The reaction mixture is distilled until the temperature reaches 150°C. On cooling, the residue solidifies and is then boiled with 1 liter of ligroin (b.p. 60°-90°C). The mixture is filtered. The remaining solids are refluxed with ligroin and then filtered. Approximately 12-18 gm (9-14%) of almost pure cyanuric acid is obtained from the ligroin-insoluble material. Dis tillation of the combined dry ligroin filtrate up to 150°C affords a residue which on distillation at reduced pressure gives 266 gm (76%), b.p. 108°-109°C (14 mm), m.p. 53°-54°C. 2-4. Preparation of 2-Ethylbutyl Carbamate [19] C2H5 CH3CH2CHCH2OH + COCl2
C2H5 >
CH3CH2CHCH2OCOCl
NHa
>
Ç2H5 CH3CH2CHCH2OCONH2
(7)
To a flask situated in a well-ventilated hood is added 1 liter of toluene. The toluene is cooled to 5°C with an ice bath and then phosgene is passed into it until 200 gm (2.0 mole) has been absorbed. To this phosgene solution is added 182 gm (1.8 mole) of 2-ethyl-l-butanol with rapid stirring. The reaction is exothermic and the temperature rises to 35°C while hydrogen chloride and some phosgene are evolved and passed through a potassium hydroxide trap. The reaction mixture is stirred for an additional 18 hr, then a dry nitrogen stream is passed through the solution for 1 hr in order to remove excess phos gene. The solution is poured, with rapid stirring, into 400 ml of concentrated aqueous ammonia, cooled to 5°C. The toluene layer is separated, concentrated under reduced pressure, and cooled in an ice bath to precipitate 195 gm (75 %), m.p. 81°C (corr.) of 2-ethylbutyl carbamate. Other carbamates such as ethyl-«-propyl, isopropyl, 3-butyl, isobutyl, secbutyl, fl-amyl, isoamyl, 2-methylbutyl, 1-ethylpropyl, and 2-ethylhexyl carb amate were prepared in a manner similar to that described here for 2-ethylbutyl carbamate in 55-76% yields [19]. Benzyl carbamate has also been reported to be prepared by this method in 91-94% yield [17]. Table III gives the preparation of several chloroformâtes and their con version into carbamates using aqueous ammonia.
240
11. 0-Carbamates TABLE IIIfl PREPARATION OF CHLOROFORMÂTES A N D CONVERSION
INTO
CARBAMATES USING AQUEOUS AMMONIA
ROCH2CH2OH + COCI2 -> ROCH2CH2OCOCl B.p., °C (mmHg)
ROCH2CH2OCOCI + NH 3 -+ ROCH2CH2OCONH2
R
Yield (%)
M.p. (°C)
CH 3 C2H5 CH3(CH2)3
93 77 91
58.7(13) 67.2(14) 93.0-93.5(14)
1.4163(25) 1.4169(25) 1.4241(25)
(C6H5)2CH
72
87.0-87.5(8.5)
1.4261(25)
nj
B.p., °C (mm Hg)
nj
46.8 — 62.2 — — 132.2-132.4 (2.5) — 133-134(2.5)
Yield (%)
— — —
13.3 39.0 63.5
—
63.5
"Data taken from Porai-Koshits and Remizov [16].
B. Reactions of Alkyl Chloroformâtes with Ammonia The ammonolysis of alkyl chloroformâtes affords an excellent laboratory method for the preparation of carbamates [16-20]. However, since phosgene is involved in the preparation of the chloroformate ester, great caution must be exercised. It is mandatory that phosgene be used in a well-ventilated hood. Where possible, the urea-alcohol method of Section A should be used because of the more favorable weight relationship of urea compared to phosgene. Assuming 100% reaction, the weight relationships given in Eqs. (8), (9), and (10) would hold. Section B : CH3OH + COCl2 32 gm
99 gm
CH3OCOCI + 2NH3 94.5 gm
34 gm
>
CH3OCOCI + HCI
(8)
94.5 gm 36.5 gm ► CH3OCONH2 + NH4CI 75 gm
(9)
53.5 gm
Section A : CH3OH + NH2CONH2 32 gm
60 gm
► CH3OCONH2 + NH 3 75 gm
(10)
17 gm
It should be noted that the method of Section A gives ammonia by-product which can be used to prepare more urea. However, Section B gives ammonium chloride, which requires costly conversion into free ammonia.
241
§ 2. Condensation Reactions
C. Reactions of Sodium Cyanate with Alcohols in the Presence of Acids Werner [21] reported that ethanol reacted with an aqueous solution of sodium cyanate and hydrochloric acid to give a 56 % yield of ethyl carbamate. Similar results were obtained with potassium cyanate [22, 23]. Tertiary alco hols were reported earlier to react with potassium cyanate in acetic acid to give dehydration or rearrangement but no carbamate [24]. Marshall [25] and others [26,27] described a method whereby tertiary alcohols reacting in situ generated cyanic acid from a mixture of anhydrous sodium cyanate in trichloroacetic acid. Loev [28] recently reported that modifying Marshall's procedure by using trifluoroacetic acid affords ί-butyl carbamates in over 90% yields. The beneficial effect of trifluoroacetic acid does not appear to be solely related to increased acid strength as hydrochloric acid or methanesulfonic acid gives only traces of carbamate when used in place of trifluoroacetic acid under similar conditions. The role of trifluoroacetic acid in the mechanism of this reaction requires further investigation. When the reaction is run in benzene and méthylène chloride, better yields are obtained than from similar reactions run in ether, tetrahydrofuran, or carbon tetrachloride. Surprisingly it was reported that when potassium cyanate is substituted for sodium cyanate the yields of carbamates are reduced to less than 5 %. The reason for this drastic effect is not known at this time. In addition, the use of other alkali or alkaline metal cyanates in this reaction has not been investi gated. The Loev [28] procedure appears applicable to the synthesis of carb amates from primary, secondary, and tertiary alcohols (2 hr reaction time affords 60-90% yields), cyclic and acyclic 1,3-diols, phenols, oximes, aldoximes, and ketoximes, and primary, secondary, and tertiary mercaptans. Carbamates could not be obtained from diphenylethylcarbinol (dehydrated to 1,1-diphenylethylene) or trichloro- and trifluoromethylcarbinols. Although earlier investigators [24, 29, 30] reported that cyanic acid reacts with alcohols to give allophonates, Loev [28] never detected any of these in his procedure. The only by-product was trifluoroacetamide, which did not present a difficulty because of its high solubility in water and organic solvents. Table IV illustrates the production of carbamates by the reaction of sodium cyanate and alcohols in the presence of trifluoroacetic acid. .2-5. Preparation oft-Butyl Carbamate [28] CH 3 CH 3 —C—OH + NaOCN CH 3
CAUTION: Use a hood.
CF3C00H _ H ► <-6 6
CH 3 O I II CH3-C-OCNH2 I
CH
,^x (11)
0.21
0.21
0.21
i-BuSH
Me | Et 2 C—SH
/ 0.20
0.20
100
0.20
100
100
CH2C12
100
100
100
100
Ether
0.20
0.20
0.20
D a t a taken from L o e v and K o r m e n d y [28].
\=NOH
0.21
«-BuSH
OH
1
Me2^/jy-Me2
T
0.21
0.21
C 6 H 5 OH
OH
0.21
CH=C—CH 2 OH
18
18
4
3
18
48
3
2
0.20
2
100 100
0.20
0.21
t-BuOH
CÓHÓ
0.20
0.21
Time (hr)
rt-BuOH
Solvent (ml)
NaOCN (moles)
CF3COOH (moles)
Alcohol
a
T A B L E IV a
30
30
30
30
30
30
30
30
30
Temp. (°Q
\=NOCONH2
Me | Et 2 C—SCONH 2
/-BuSCONH 2
K-BuSCONH2
/
2
OCONH 2
1
Me2-^N-Me
OCONH 2
C 6 H 5 OCONH 2
90
25
50
65
45
62
60
92
CH=C—CH 2 OCONH 2
73
A*-BUOCONH2
Yield (%)
r-BuOCONH 2
Product carbamate
94-96
45-47
92-95
98-100
175-185
145-148
H20
Hexane
Hexane
Hexane
H20
H20
Benzene
Hexane 47-50
H20 53-54
Recryst. solvent
107-108
M.p. (°C)
SYNTHESIS OF CARBAMATES VIA THE R E A C T I O N OF S O D I U M C Y ANATE A N D A L C O H O L S I N THE PRESENCE OF TRIFLUOROACETIC A C I D
243
§ 2. Condensation Reactions
To a stirred mixture of 7.4 gm (0.1 mole) of /-butyl alcohol and 13.0 gm (0.2 mole) of sodium cyanate in 50 ml of benzene is slowly added 15.5 ml (0.21 mole) of trifluoroacetic acid. The reaction is exothermic and some gas bubbles are formed. The reaction is stirred for 3 hr, then 15 ml of water is added, the organic layer separated, dried, the solvent removed under reduced pressure at a pot temperature of 40°-50°C ; the resulting residue solidifies to afford 10.7 gm (92%), m.p. 98°-10rC. Recrystallization of the entire product from water affords 8 gm (69%), m.p. 107°-108°C. D. Transesterification of Carbamates Carbamates have been prepared by heating ethyl carbamate with a higherboiling alcohol in the presence or absence of catalysts [31-33]. Aluminum isopropoxide has been reported [34] to be an excellent catalyst for the interchange reaction between ethyl carbamate and benzyl alcohol. The interchange reac tion is also effective for N-alkyl carbamates as well as unsubstituted carb amates [35]. This catalyst is effective in preparing mono- and dicarbamates in excellent yields from primary and secondary alcohols and diols. Other effec tive catalysts are: dibutyltin dilaurate [36], dibutyltin oxide [37], sulfuric acid or/7-toluenesulfonic acid [31], and sodium metal (reacts with alcohols to give the alkoxide catalyst) [33]. Examples of the transesterification reaction of ethyl carbamates and alco hols are given in Table V. TABLE \Ta TRANSESTERIFICATION REACTION OF ETHYL CARBAMATES AND ALCOHOLS
Alcohol Isobutyl
sec-Butyl /-Butyl Benzyl
a
Mole ratio of ethyl carbamate/ alcohol Catalyst 1/6 1/6 1/6 1/6 1/6 1/1.5 1/1.5 l/lc
O H2S04e (fl-Bu) 3 N
H2S04 H2SO4
O H2SO4
Al (iso-PrO) 3
Temp. (°C)
Time (hr)
Yield (%)
110-120 110-120 110-120 105-110 85-90 190-230 145-240 130-140 d
103 19 8 16
— 87 (56)& — 37
—
19 5 5-10
—
70 (53)b 9 86
Data taken from Gaylord and Sroog [31] except where noted. Recrystallized product. c Data from Kraft [34]. d Bath temperature. e Approximately 2 ml concentrated H2SO4/0.5 mole ethyl carbamate used. b
M.p. (°Q
— 63-64
—
92-93
—
85-86 82-84 86-87
244
11. 0-Carbamates
Tertiary alcohols and phenols do not undergo the transesterification reaction of carbamates with acidic or basic catalysts [38]. 2-6. Preparation of Benzyl Carbamate [34] O II
C2H5OCNH2 + C6H5CH2OH
Al(iso-PrO) 3
-+
O 'I
C6H5CH2OCNH2 + C2H5OH
,
(12)
To a 250 ml three-necked flask equipped with a thermometer and a 20 cm distillation column filled with glass beads are added 44.5 gm (0.5 mole) of ethyl carbamate, 54.1 gm (0.5 mole) of benzyl alcohol, and 60 ml of toluene. The reaction flask is heated with an oil bath at 110°-125°C in order to remove any water in the reagents. The bath is cooled to 100°C, and 2.0 gm (0.01 mole) of aluminum isopropoxide is added all at once. The reaction is heated with the oil bath set at 130°-140°C in order to remove about 50 ml of the ethanoltoluene azeotrope at 77°C. The residue is recrystallized from toluene to yield 64.5 gm (85.5%), m.p. 86°-87°C. NOTE: Substituting sodium methoxide for aluminum isopropoxide gave poor yields. 3. MISCELLANEOUS METHODS (1) Ammonolysis of diethyl carbonate to ethyl carbamate [39]. (2) Preparation of tertiary alkyl esters of carbamic acid by the ammono lysis of mixed phenyl alkyl carbonates to yield alkyl carbamate and phenol [24, 40, 41]. (3) Reaction of urea and ethylene oxide to give aminoethyl carbamates [42]. (4) Reaction of carbamoyl chloride (NH 2 COCl) with alcohols to yield carbamates [43]. (5) Reaction of alkyl oxamates with bromine and sodium ethoxide [44]. (6) Reaction of silver carbamate with alkyl halides [45]. (7) Hydrolysis of cyanates [46]. (8) Reaction of polyvinyl alcohol with urea to give polyvinyl carbamates [11,47,48]. REFERENCES
1. F. M. Berger and B. J. Ludwig, U.S. Pat. 3,724,720 (1956). 2. R. L. Arcenaux, J. G. Frick, H. O. Reid, and G. A. Gantreaux, Amer. Dyest. Rep. 50, 37 (1961). 3. Berkeley Chemical Corp., Liquithane, Bulletin, 1960. 4. I. H. Updegraff and A. Contras, U.S. Pat. 2,937,966 (1960). 5. R. T. Pollock, U.S. Pat. 2,438,452 (1948).
References 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48.
245
P. Kirby and T. Owen, Brit. Pat. 961,569 (1964). R. A. Jacobson, / . Amer. Chem. Soc. 60, 1742 (1938). T. L. Davis and S. C. Lane, Org. Syn. Coll. Vol. 1, 140 (1941). A. E. A. Werner, /. Chem. Soc. 113, 622 (1918). F. M. Meigs, U.S. Pat. 2,197,479 (1940). M. Paquin, Z. Naturforsch. 1, 518 (1946). S. Beinfest, P. Adams, and J. Halpern, U.S. Pat. 2,837,561 (1958). F.. J. Sowa, U.S. Pat. 2,834,799 (1958). L. I. Smith and O. H. Emerson, Org. Syn. Coll. Vol. 3, 151 (1955). M. T. Harvey and S. Caplan, U.S. Pat. 2,247,495 (1941). H. G. Ashburn, A. R. Collett, and C. L. Lazzell, /. Amer. Chem. Soc. 60, 2933 (1938). H. E. Carter, R. L. Frank and H. W. Johnston, Org. Syn. Coll. Vol. 3, 167 (1955). G. A. Kirkhgof and R. Y. Astrova, Khim. Farm. Prom. 282 (1933). W. M. Kraft and R. M. Herbst, J. Org. Chem. 10, 483 (1945). J. Thiele and F. Dent, Ann. Chem. 302, 246 (1898). E. A. Werner, Sci. Proc. Roy. Dublin Soc. 24, 209 (1947). O. Folin, Amer. Chem. J. 19, 336 (1897). J. H. Barnes, M. V. A. Chapman, P. A. McRea, P. G. Marshall, and P. A. Walsh, / . Pharm. Pharmacol. 13, 39 (1961). W. M. McLamore, S. Y. P'An, and A. Bavley, / . Org. Chem. 20, 1379 (1955). P. G. Marshall, J. H. Barnes, and P. A. McCrea, U.S. Pat. 2,814,637 (1957). W. Stuehmer and S. Funke, U.S. Pat. 2,878,158 (1959). J. H. Barnes, /. Pharm. Pharmacol. 13, 39 (1961). B. Loev and M. F. Kormendy, / . Org. Chem. 28, 3421 (1963). W. J. Close and M. A. Spielman, /. Amer. Chem. Soc. 75, 4055 (1953). K. W. Blohm and E. I. Becker, Chem. Rev. 51, 471 (1952). N. G. Gaylord and C. C. Sroog, /. Org. Chem. 18, 1632 (1953). G. Heilner, Ger. Pat. 551,777 (1932). M. Metayer, Bull. Soc. Chim. Fr. 802 (1951). W. M. Kraft, /. Amer. Chem. Soc. 70, 3569 (1948). R. Hazard, J. Cheymal, P. Charbrier, A. Skera, and E. Echefralaire, Bull. Soc. Chim. Fr. 2087 (1961). W. Kern, K. J. Ranterkus, W. Weber, and W. Herz, Makromol. Chem. 57, 241 (1962). P. Adams and F. A. Baron, Chem. Rev. 65, 570 (1965). N. G. Gaylord, / . Org. Chem. 25, 1874 (1960). A. Cahours, Ann. Chem. 56, 266 (1845). K. Hafner and W. Kaiser, Tetrahedron Lett. 32, 2185 (1964). Société des Laboratoires Labaz, Brit. Pat. 802,557 (1959). W. F. Touisignant and T. Houtmann, Jr., U.S. Pat. 2,842,523 (1958). L. Gatterman, Ann. Chem. 244, 29 (1888). J. Miliotis, Prakt. Akad. Athenon 10, 190 (1935). U. Iwase, Japan. Pat. 17,655 (1963). D. Martin, Angew. Chem. 76, 303 (1964). I. Sakurada, A. Nakajima, and K. Shibatani, /. Polym. Sci. A 2, 3545 (1964). F. Masuo and T. Watanabe, Japan. Pat. 13,886 (1960).