ADDITIONREACTIONS OF 1-CYANO-1,3-BUTADIENE
Jan., 1950
several a-keto esters has been investigated. The type and yield of the isomers produced were found to be influenced by the acidity of the medium, the
[CONTRIBUTION FROM
THE
81
nature of the ketonic reagent and the nature of the pyrimidine. TUCKAHOE 7, NEWPORK
RECEIVEDJULY 26, 1949
SCHOOL OF CHEMISTRY AND PHYSICS, THEPENNSYLVANIA STATECOLLEGE,AND DEPARTMENT O F CHEMISTRY, STANFORD UNIVERSITY]
THE
Addition Reactions of 1-Cyano-1,3-butadiene1t2
s.
BY MILTONFRANKEL,3'4HARRY MOSHER AND FRANK c. WHITMORE'
Previous reports6v7**Jof reactions of l-cyano1,3-butadiene have not included any study of the addition of amines to this substance. We have found that diethylamine, morpholine and piperidine rapidly add a t zero degrees to give excellent yields of the 1-cyano-4-substituted-amino-2-b~tenes (11, 111, IV); nmo catalyst other than the amine itself is required.
good yields in the presence of Raney nickel catalyst to give the 5-substituted-amino-1-aminopentanes (VII). Were it not for the present difficulty in obtaining large amounts of the necessary 1cyano-l,3-butadiene, this would constitute an excellent preparative method for these otherwise difficultly obtainable products. In the reaction of excess piperidine with 1cyano - 1,3- butadiene CHz=CHCH=CHCN HNR, +R2NCH2CH=CHCH2CN I1 -NRz = -N(CeH& at 5-10" an 11% III-NRz = -NC~HIO crude yield of the I I V -NRz = -NCaHlo product, l-cyano-2,4d i piperidinobutane, Cl(CHz)&N HNRz -+RzN(CHz)XN + RzN(CHz)gNHz resulting. from the adv VI VI1 dition ouf two moles of The actual position of the double bond in these the amine, was obtained. 1-Cyano-4-piperidinoproducts (11, I11 and IV) has not been proven 2-butene was refluxed with excess piperidine for but the well-established course of such additions twelve hours; a 43% yield of l-cyano-2,4-diwould indicate that ii; is situated in the @,r-piperidinobutane was isolated and the remainder position as represented. Attempts to rearrange of the starting material was recovered unchanged. IV into VIII, in which the double bond is conju- Several attempts to increase this yield by the gated, were unsuccessful ; polymer or unchanged use of a strongly basic catalyst such as sodium starting material was recovered. The maximum methylate or Triton B were unsuccessful; yields in the ultraviolet absorption spectrum was below of 10 to 20% were obtained (20 to 35% con215 mp and could not 'be conveniently measured. sidering starting material which was recovered). Comparison of infrared absorption spectra for In these experiments a certain amount of nonI, IV and VI was indicative of an isolated double volatile polymer was always formed. It is bond but could hardly be considered definitive postulated that piperidine itself is a strong enough since the geometry around the double bond is base to catalyze the rearrangement of the 1unknown. Since careful reduction with hydrogen cyano4-piperidino-2-buteneto the conjugated in the presence of platirium catalyst has given the l-cyano-4-piperidino-l-butene (VIII) which then same substituted 4-amino-1-cyanobutanes (VI) adds a second mole of the piperidine to give as produced from 4-chloro-1-cyanobutane (V) IX. and the correspondNCsHio ing secondary amine, "CaHio H N CsHm l there can be no doubt IV [C5HloN-CH2CHzCH=CH-CN] ___) C5HloNCHzCH-CH2CN concerning the termiVI11 IX nal position of the secondary amino group. Either the saturated H o m e r , it was not possible to accomplish the or unsaturated b-aminonitriles were reduced in addition of a second molecule of either morpholine OT to the corresponding 1-cyano-4(1) Taken in part from the 16. S. Thesis of Milton Frankel, The amino-%butene by heating without catalyst even Pennsylvania State College, June, 1947. (2) Presented before the Organic Division of the American Chemiin a sealed tube a t 120°. Bv the use of Triton B cal Society a t the New York meeting, September 17, 1947. as a catalyst, addition occurred a t room tempera(3) Parke, Davis and Co. Reliearch Fellow 1947-1949. ture With the formation Of pDor yields Of (4) Present address: Aerojet Engineering Corp., Azusa, Calif. ( 5 ) Deceased, Harvard Unkersity Ph.D. 1914. 2,4-dimorpholinobutane and l-cyano-2,4-di-(di(6) Coffman, THISJOURNAL, 67, 1981 (1935). ethy1amino)-butane. The necessky of a basic (7) Charlish, Davies and Roae, J . Chcm. Sac., 227-234 (1948). catalyst in these two cases constitutes circumstan(8) Bruson, U. S. Pat. 2,466,679,1949. bond was Original1? (9) Snyder, Stewart and Myers, THISJOURNAL, 71, 1055-1056 tial evidence that the present in the non-conjugated position. (rs49).
+
+
/
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-
dkthwine
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MILTONF R A N K E L , HARRY
s. MOSHERAND h 'L'AI3I.F.
Refract.
Compound, 1-cyano-%butenes
Yield,
70 82.7 4-Piperidino89.5 4-Morpholino4-Diethylamino- 80.0
B. P . .
OC.
Mm.
106109 114-119 83-95
5 3 3
indes. iz%
Picrate m. p . . 'C.
1.4S65 130-131 1.4872 174-175 1.4591 90-92
N K
c. WHITMORE
Vol. 72
I Analyses, % Carbon Hydrogen Calcd. Found Calcd. Found
7 -
S e u t . equiv. Calcd. Found
Formula
164 164.0 CIOH~&'-I 73.12 72.89 9.82 9.65 166 165.7 CoHicON'z 65.03 65.34 8.49 8.32 71.00 71.14 10.60 10.26 152 154.8 CoHiiNn
1-Cyanobutanes
86.2' 106-109 4-Piperidino80.6d 110-115 4-Morpholino4-Diethylamino- 46.1d 67-70
II
1.4659 123-123.5 3 1.4650 121-121.5 8 1.4444 3
1-Aminopentanes
78.5 72-83 3 1.4750 139-140 85 85.0 CioHd'z 70.52 70.99 13.02 12.64 5-Piperidino-' 63.0 111-126 5 1.475 144-145 86 86.2 C~iHzaN8011140.00 40.30 4.16 4.27 5-Morpholino79 80.8 5-Diethylaminoc 76.6 106-115 32 1.4485 * Hydrochloride derivative m. p. 150-151°. Anal. Calcd. for Cd-I1&HC1: C1, 17.5. Found: 17.3. Chloroplatinate, m. p. found 221-224' dec. Manasse, Ber., 35 1370 (1902), reports a m. p. of 228" dec. for this derivative. Magidson and Gregorowsky, ioid., 69B, 396 (1936). These are the yields obtained by the reaction of l-cyano-4chlorobutane with the secondary amine. The yields obtained by the catalytic reduction of the corresponding butenes This analysis is on the dipicrate derivative. were SC-9OCfo.
Methanol added to l-cyano-4-piperidino-2butene (IV) in the presence of sodium methylate to give an 80%. yield Of purified 1-cyano-2methoxy-4-piperidmobutane (X).
perature was maintained a t 5-10", 76.5 g . (0.9 mole) of redistilled piperidine was added. The addition, which was accompanied by an exothermic reaction, required one hour. After remaining for thirty-six hours a t 10"the mixture was distilled giving 115.3 g. of product, 82.7y0 yield. Morpholine and diethylamine underwent reaction OCHa in a similar manner. Properties and yields are given in Table I. The reaction was probIv OCHa- [vIIIl HOCH, C6Hlor\l'-CH2CH2-CH-cH*~~ I ably comdete in two to three hours in the OCI-13cold but t h e reaction mixtures were always The l-cyano-1,3-butadiene was prepared both stored for a time as indicated above, since this procedure was found to result in better yields in the analogous addiby the pyrolysis of the benzoate of crotonaldehyde tion of secondary amines to acrylonitrile. cyanohydring,lo and by the dehydration of butaIf an excess of piperidine was employed, the reaction was diene cyanohydrin." complicated as indicated in the following experiment. It was realized during this investigation that the When 0.79 mole of l-cyano-1,3-butadiene and 3 moles of were allowed to react essentially as described l-cyano-1,3-butadiene being used must be a piperidine above, there was obtained 78.2 g . (62.5%) crude yield of mixture of both cis and trans forms.g However, l-cyano-4-piperidino-2-butene as well as 22 g. (12% yield) careful fractionation always resulted in the pref- of crude l-cyano-2,4-dipiperidinobutane,b. p. 175' (3 ~ D neutral equivalent found (on titration t o erential polymerization of the high refractive mm.), I ~ 1.497, orange end-point in 50% ethanol) 126.3, calculated index form, leaving as much as 50% of the charge methyl 124.5. The picrate derivative, m. p. 151.5-162' was as a non-volatile residue. The material used in analyzed. the earlier experiments was carefully fractionated Anal. Calcd. for C 1 ~ H S ~ N C,~45.83; : H, 470. Found: and therefore corresponded closely in properties C, 45.77; H, 4.64. to the substance reported by Snyder, et U Z . , ~ as Even when an excess of morpholine or diethylamine was the cis isomer. In the later experiments a mix- employed no diaddition product was isolated. The Reaction of Secondary Amines with the 1-Cpano-4ture of isomers boiling between fifty and sixty substituted amino - 2 butenes.-1 Cyano-4-piperidino-2degrees at thirty-five millimeters pressure was butene (IV), 5 g . (0.03 mole), was stirred with piperidine, used. No apparent difference was noted in the (0.09 mole), while the solution was refluxed for ten hours. reactions of these two materials with the second- Distillation of the reaction mixture from a Claisen flask gave approximately 3 g. of recovered IV, b. p. 83-94' ary amines. (2 mm.), n% 1.4880-1.4901, and 3.2 g. of 1-cyano-2,4Acknowledgment.-We wish to thank Parke, dipiperidinobutane (VIII), b. p. 174-176" (2 mm.), ?PD Davis and Company, whose support made this 1.4953. Based on IV taken the yield is about 43710; work possible, and the Columbia Chemicals considering recovered IV the yield is quantitative. Similar experiments with morpholine and diethylamine failed to Division of Pittsburg Plate Glass Company, and give any addition of the second molecule of the amine. A in particular Dr. William E. Bissinger, for a reaction conducted with morpholine and I11 in a sealed tube at 120' for eleven hours gave no addition product and generous supply of -butadiene cyanohydrin. 75y0 of I11 was recovered. Experimental Several attempts were made to increase the yield by Reaction of Secondary Amines with l-Cyano-l,3-buta- addition of a more strongly basic catalyst. Piperidine, diene .-In a 500-ml. three-necked flask equipped with 17 g. (0.20 mole), was mixed with IV, 16.5 g. (0.10 mole), mechanical stirrer, thermometer and dropping funnel was and one drop of Triton B (40T0 solution of trimethylbenzyl ammonium hydroxide). After the mixture had remained placed 67.4 g. (0.85 mole) of l-cyano-1,3-butadiene (b. p. 50-80' (35 mm.), ~ z . ~1.4912). D While the tem- at 10" for five days and at room temperature for one day, it was distilled, giving 11.8 g. (72%) of recovered IV and (10) Gudgeon, Canadian Patent 388,840, Aug. 26 (1940 2.4 g . (10%) of VIII. The yield, considering recovered (1 1) Bissinper. st ol.. THISJOURNAL, 69, 2958 (1947). startlng material, was 33%. The use of either a higher
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Jan., 1950
ADDITIONREACTIONS O F 1-CYANO-1,3-BUTADIENE'
temperature or more catalyst resulted in lower yields and greatly increased amounts of nondistillable residues. Although the yields were poor, the use of Triton B as a catalyst made possible the addition of a second molecule of diethylamine or morpholine to I1 and 111, respectively. Thus 15.2 g. of 11, 14.6 g. of diethylamine and one drop of Triton B gave 11.6 g. of recovered 11,1.5g. of the addition product, presumably l-cyano-2,4-di-(diethylamino)-butane, b. p. 155-160' (0.1 mm.), t t B O ~1.4808, and 1.8 g. of residue. Similarly 16.6 g. of 111, 17.4 g. of morpholine and one drop of Triton B gave 3.3 g. of the addition product (presumably l-cyano-2,4-dimorpholinobutane), b. p. 195-200" (0.6 mm.), TPD 1.5124 as a viscous yellow oil and the remainder was a nondistillable polymer. Crystalline picrates could not be prepared of either of these two addition compounds and they undoubtedly were impure. l-Cyano-2-methoxy-4-pi eridinobutane.-Into a mixture of 14.2 g. (0.44 mole7 of absolute methanol and 0.8 g. (0.015 mole) of sodium methylate in a 100-ml. flask was dropped 16.4 g. (0.10 mole) of l-cyano-4-piperidino-2butene over a thirty-minute period; there was no appreciable evolution of heat. The reaction mixture was stirred for two hours, allowed to remain at room temperature for ten hours and worked up by neutralization of the base with 0.4 ml. (0.0075 mole) of concentrated sulfuric acid. filtration and distillation. After the alcohol was removed, only one material distilled, b. p. 152-153 o (3 mm.), ~ Z 1.4883, ~ D 15.7 g. (80%). The picrate, m. p. 143.0143.5', was analyzed. Anal. Calcd. for ClrHaNaOs: C, 48.00; H, 6.45. Found: C, 48.30; H, 5.49. Preparation of the 1-Cyano-4-substituted-aminobutanes.-The products from the addition of piperidine, morpholine and diethylamine to l-cyano-l,3-butadiene were each reduced catalytically in ethanol solvent under three atmospheres pressure of hydrogen in the presence of Adams catalyst. At room temperature absorption of hydrogen proceeded only until one mole was absorbed. The boiling points and refractive indices of these products agreed very closely to the corresponding properties of the same products made from 1-chloro-4-cyanobutane and the respective secondary amine as indicated below. The picrates of the products made by these two different methods melted a t the same temperatures (see Table I) and these melting points were undepressed by mixing. A mixture melting point of the picrate of 1-cyano-4-morpholinobutane (m. p. 120.5-121.5') and picric acid (m. p. 122') was greatly depressed, as was also the melting point of a mixture of l-cyano-4-piperidinobutane(m. p. 122.5-123.5") and picric acid. 1-Cyano-4-substituted-aminobutanesfrom l-Cyano-4ch1orobutane.-Piperidine, morpholine and diethylamine were refluxed with S-chlorovaleronitrilel* in dry benzene as already described for the next lower homolog.1s The yields and properties are given in Table I. Reduction of 1-Cyano-4-substituted-aminobutanes to the Corresponding 5-Substituted -0-1 -aminopentanes. (12) Starr and Hlxon, THISJOURNAL, 66, 1595 (1934). (13) Whitmore, Mosher, et al., ibid., 86, 725 (1944).
83
-The products resulting from the addition of the secondary amines to l-cyano-1,3-butadiene were catalytically reduced in absolute alcohol solvent which was saturated with ammonia. The reductions were conducted with initial hydrogen pressures of 2000 p. s. i., temperatures of 90-looo, and in the presence of Raney nickel catalyst. The properties of the resulting 5-amino-1-arninopentanes are given in Table I. 2-Methoxy-6-chloro-9-( +piperidmoamyl) -aminoacridine.-The 5-piperidino-1-aminopentane, 8.5 g. (0.05 mole), from the above reduction was added to a mixture of 6,9-dichloro-2-methoxyacridine,13.9 g. (0.05 mole), in 60 g. of phenol. After three hours of heating on the steambath, the mixture was poured into 500 ml. of 2 N sodium hydroxide, and extracted with 500 ml. of chloroform in three portions. The chloroform extracts were shaken with 10% acetic acid and the acetic acid extracts treated with ammonium hydroxide. A yellow oil separated which was converted to the hydrochloride by dissolving in absolute ethanol and bubbling in dry hydrogen chloride gas. The product owas twice crystallized from ethanol; 11 g., m. p. 237-238 Anal. Calcd. for C24H3PON&!14: N, 8.06. Found: N, 7.98. A mixture melting point with this material and the product made in the same manner, from 5-piperidino-1-aminopentane prepared by another method,'* was undepressed.
.
Summary 1. Three secondary amines, piperidine, morpholine and diethylamine, have been shown to react with l-cyano-1,3-butadiene to give l-cyano4-amino-2-butenes in good yields. 2. A second molecule of the secondary amine will react in the presence of an added basic catalyst to give l-cyano-2,4-diaminobutenes but with more difficulty. 3. The l-cyano-4-amino-2-butenesmay be reduced catalytically either to 1-cyano-4-aminobutanes or to eaminoamylamines. 4. In the presence of sodium methylate, methyl alcohol will add to l-cyano-4-piperidino-2butene to give 1-cyano-2-methoxy-4-piperidinobutane. These reactions offer possibilities of synthesizing various di-functional derivatives of valeronitrile and amylamine which are otherwise very difficultly accessible. STATE COLLEGE, PENNSYLVANIA STANFORD, CALIFORNIA RECEIVEDJULY 18, 1949 (14) E. C. Chapin, Ph.D. Thesis, The Pennsylvania State College, Oct. 1944, p. 98. The melting point reported here waa 140° hut this particular sample WM found to melt at 237-238O when the melting point was redetermined at a later date.
