H. R.
4230
S N Y D E R AND JAMES
As in Table I 1 the uncertainty in these values is several tenths of a unit.
H. BREWSTER
Vol. 70
Let us define y = 2 a ( b / ~ k T ) ' /in~ terms , of which the thermodynamic functions may be written as
TABLE IV CYCLOHEXENE, THERMODYNAMIC FUNCTIONS (Units: cal./degree mole)
-- - rf3
T, OK.
200 298.16 300 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500
- ( p - H$
T
09
10.75 13.98 14.05 18.04 22.20 26.20 29.93 33.35 36.47 39.33 41.94 44.34 46.53 48.55 50.42
16.32 25.10 25.28 34.64 42.78 49.45 54.92 59.49 63.34 66.62 69.43 71.85 73.92 75.72 77.27
T
9
T
55.43 60.29 60.38 64.96 69.43 73.84 78.16 82.38 86.49 90.48 94.36 98.12 101.75 105.27 108.68
66.18 74.27 74.43 53.00 91.63 100.04 108.09 115.73 122.96 129.81 136.30 142.46 148.28 153.82 159.10
Appendix I In order tcr calculate thermodynamic functions for the mode of osdllation with potential energy given by equation ( 2 ) above, the partition function is needed
On integration the result is Q =
(2?rmkT)'/z h [%a f (?rkT/b)'/Z)
[CONTRIBUTION FROM
THE
(4)
Summary
By the use of bond bending and bond twisting (internal rotation) potential constants from related molecules the potential or strain energy of cyclopentene and cyclohexene was calculated for various configurations. It was found that cyclopentene can pucker by moving the carbon opposite to the double bond out of the plane of the other four carbon atoms by about 0.3 A. without significant change in energy from the planar configuration. Cyclohexene, by contrast, shows two tautomeric forms related to chair and boat cyclohexane which differ by about 2.7 kcal ./mole. The available Raman and infrared spectroscopic data are interpreted for cyclopentene and cyclohexene. With reasonable adjustments of otherwise somewhat uncertain parameters, agreement is obtained with the thermodynamic data for the two substances. The thermodynamic functions (- (Fo - H:)/T, (Ho - H,)/T, So and Ci) are then calculated for the ideal gas state from 200 to 1500OK. BERKELEY, CALIFORNIA
RECEIVED AUGUST7, 1948
NOYESCHEMICAL LABORATORY, UNIVERSITYOF ILLINOIS]
Amine Exchange Reactions of Mannich Bases BY H. R. SNYDER AND Amine exchange reactions occur when quaternary ammonium salts are heated with ammonia or primary or secondary amines2 (eqn. Al). Similar reactions have been observed with Mannich bases of nitromethane3 and of indole* (eqn. B l ) ; the phenylhydrazones of ketonic Mannich bases form pyrazolines by internal amine exchange5 (eqn. C). (1) Present address: Department of Chemistry, University of Chicago, Chicago, Illinois. (2) Scholtz., Btr., 94, 2402 (1891); 31, 414, 1700 (1898); von Braun and Zohel, Ann., 445, 247 (1925); Ber., 59, 1786 (1926); von Braun, Kuhn and Goll, ibid., 59, 2330 (1926); Hultquist, cf a!., THISJOURNAL, 70, 23 (1948). (3) Duden, Bock and Reid, Bcr., 38, 2036 (1905). (4) Howe, Zambito, Snyder and Tishler, THISJOURNAL, 67, 38 (1945). (5) Mannich and Bauroth, Bcr., 67, 1108 (1924); Xisbet and Gray, J . Chcm. Soc., 839 (1933); Levvy and Nisbet, ibid., 1053,1572 (1938); Nisbet, ibid., 1237, 1568 (1938); 126 (1945); Harradence and Lions, J . Proc. Roy. SOC.N. S, Wales, 73, 14 (1939) [C.A . , 33, 8196 (1939)l.
JAMES
H. BREWSTER~
Since these reactions appear to be similar in their mechanisms to the corresponding amine replacement reactions which occur in alkylations with quaternary salts of benzylamine6*'J' (eqn. A2), and with Mannich (eqn. B2) and their quaternary saltss*10(eqn. A2), it seemed desirable to determine whether amine exchange reactions occur readily with ketonic and phenolic Mannich bases. A.
+
1 R'-NRs
+ : B +R'B+ + : NRs
R' = ~ - c H ? - - , CH~-, etc.; B = H N R ~ " (6) von hleyer, Abhandl. math.-$hys. Klasse szchs. Akad. Wiss.. 31, 179 (1908) [Chem. Zsntr., 80, 11, 1800 (1909)l. (7) Snyder and Speck, THISJOURNAL, 61, 668, 2895 (1939). (8) Snyder, Smith and Stewart, ibid., 66, 200 (1944). (9) Mannich, Koch and Borkowsky, Bcr., 70, 355 (1937); Reichert and Posemann, Arch. Phavm., 976, 67 (1937). (10) duFeu, McQuillin and Robinson, J . Chcm. SOC..53 (1937).
Dec., 1948
AMINE EXCHANGE REACTIONS O F MANNICH BASES NRF
2
a. -N(CHa)z
b.
B = -CH(COzEt)2, -cN, R’NR2 HB +R’B
-NW / 7 0 c.
-62
etc.
+ HNRz
+
B.
4231
NO,
1.
v
I
RzN-CH2-CH-CHzH HB = HNRz“
-NRz=
a.
b. --N
2.
2.
VI -N(CH&;
IV
-.’> R‘=O; -;
1. R’=H;
-NR-
b, -N
/ 7
0
u
c.
/ 7
\-/
0;
c
\-
a. - - N ( C H ~ ) ~ ;
d. -NHz
It was found that P-dimethylaminopropiophenone (Ia) reacts with boiling morpholine (IVb) to form /3-morpholinopropiophenone (Ib) and diC. methylamine (IVa). The hydrochloride and methiodide of Ia reacted only a little more rapidly with morpholine than did the tertiary amine (Ia) Ar Ar Similarly, a-dimethylaminomethyl-@-naphthol (V la) reacted by amine exchange with morphoIn common with other @-aminoketones, the line and with piperidine (IVc). The morpholine Mannich bases of ketones (I) undergo amine and piperidine Mannich bases of /?-naphthol (V elimination reactions to form a,&unsaturated car- l b and V IC) could be converted one to the other bonyl compounds (I1I).l1 Ammonia and pri- by reaction with an excess of the appropriate secmary and secondary amines add in a 1,4 manner to ondary amine. a,@-unsaturatedketones,l* perhaps by way of a The Betti bases (V 2) formed by condensation of six-membered chelate ring intermediate (11) such P-naphthol with benzaldehyde and ammonia or dias that suggested by Cromwell and Cram.l8 This methylamine likewise reacted by amine exchange intermediate could also participate in amine elimi- with morpholine and with piperidine. nation reactions; if so, bimolecular amine exGood yields of pure products were obtained in change reactions would be expected to occur all cases when one of the secondary amines was readily with ketonic Mannich bases (eqn. D). present in large excess or when dimethylamine or o-Aminomethylphenols (V) are essentially eno- ammonia was removed from the mixture by volalic forms of ketonic Mannich bases. The phenolic tilization. Side reactions and resin formation were hydrogen atom appears to be bound largely to the not observed, even when no inert gas was passed nitrogen atom.I4 Amine exchange reactions through the system. would be expected to occur with particular ease Experimental with such compounds, perhaps by way of a methylKetonic Mannich Bases (Ia, Ib) .-The hydrochlorides ene quinone (VI) (eqn. E). HB = HZC(CO2Et)2 HCN, etc.
.
D.
NRz I -
0 ll I
I1
R‘ =
D-
I11
IV
(11) Blicke, “Organic Reactions,” Vol. I, John Wiley and Sons, Inc., New York, N.Y..1942,p. 303 (12) Cromwell, Chem. Reus., 38, 83 (1946). (13) Cromwell, and Cram. TEIS JOURNAL, 66, 301 (1943). (14) Decombe, Comfit. rend., 191, 268 (1933); German Patent 89,979; Frdl , 4,98 (1899).
of B-dimethylaminopropiophenone (la) 16 and &morpholinopropiophenone (Ib) 16 were prepared from acetophenone, paraformaldehyde and the appropriate secondary amine hvdrochloride. The thrice-distilled.1’ free tertiarv amines had the following properties. Ia- nmD 1,5299; dZ0, 1.017;18 R M D calcd. 53.34; R M D found, 53.82; b. p. 94-97’ (7 mm.), 83-87’ (1-2 mm.) [lit.16 110-112” (14 mm.)]; hydrochloride, m. p. 156°.1671s Ib: n z o ~ 1.5433; dwp 1.10318; R M D calcd. 62.73; R M D found 62.02; b. p. 83’ (1.5 mm.); hydrochloride, m. p. 177’.16 Reactions of 8-Dimethylaminopropiophenoneand its Salts with Morpho1ine.-j3-Dimethylaminopropiophenone (Ia) (0.18 g., 0.001 mole) was heated with morpholine (4.35 g., 0.050 mole) under reflux in an atmosphere of nitrogen fQr two hours. Water (10 ml.) and 10% sodium (15) Mannich and Heilner, Ber., 56, 356 (1922). (16) Harradence and Lions, J . Proc. Roy. SOC.N . S. Wales, T2, 233,273,284 (1939)[C. A , , 33, 5855,6841.6825 (1939)l. (17) A distillation flask with a wide side-arm (10 mm.) set near the bulb was used. (18) Fischer-Davidson Gravitometer. (19) All melting points are corrected.
Vol. 70
H.R. SNYDER AND JAMES H.BREWSTER
4232
hydroxide (1 ml.) were added to the cooled solution, and the mixture was extracted with three 5-ml. portions of ether. The ether solution was dried over magnesium sulfate, filtered and treated with dry hydrogen chloride. The white precipitate was collected by filtration and crystallized from alcohol-ether to yield the hydrochloride of @morpholinoproeophenone (Ib) ; weight 0.20 g. (78%), m. p. 175-176 No melting point depression occurred when this material was mixed with authentic I b hydrochloride; marked melting point depressions (20-30 ") occurred when it was mixed with the hydrochloride of Ia or with morpholine hydrochloride. @-Dimethylaminopropiophenone (Ia) hydrochloride (0.22 g., 0.001 mole) was heated with morpholine (4.35 g., 0.050 mole) for one and one-half hours. The reaction mixture was worked up as described above to yield the $ydrochloride of Ib, weight 0.20 g. (78%), m. p. 175-177 The methiodide of Ia (0.32 g., 0.001 mole) was heated with morpholine (4.35 g., 0.050 mole) under nitrogen. The reaction appeared to be complete after 3n hour. The hydrochloride of Ib, 0.21 g. (SI%), m. p. 175-176", was isolated from the reaction mixture as described above. Phenolic Mannich Bases (V 1).-The Mannich bases of @-naphthol (V 1) form rapidly in good yield when one equivalent of 38% formalin is added to a solution of equivalent amounts of @-naphthol and a secondary amine in water or alcohad. The following were prepared: a-dimethylaminomethyl-@-naphthol (V l a ) , yield SO%, m. p. 76.0-76.5°;14 a-piperidinomethyl-@-naphthol(V2c) ,yield 73%, m. p. 9;3-94°;14**0 and a-morpholinomethyl-@naphthol (V lb), yield 9070, m. p. 116.5-117.0°.21 Amine Exchange Reactions of Naphthol Mannich Bases (V 1) .-a-Dimethylaminomethyl-@-naphthol (V la) (1 g. 0.005 mole) was heated under reflux with an excess of a secondary amine (0.025 mole) until the evolution of dimethylamine had ceased (about one hour). A slow stream of nitrogen was passed through the system to sweep out the dimethylamine formed by the reaction. Water (5 ml.) was added to the cooled residue, and the solid which precipitated was crystallized from alcohol. The products were identified by melting point and mixed melting point. With piperidine as the secondary amine, 1.12 g. (92%) of a-piperidinomethyl-@-naphthol (V IC), m. p. 93-94', was obtained. With morpholine as the secondary amine, 1.0 g. (83.5%) of a-morpholinomethyl-@-naphthol (V lb), m. p. 116.5117.0", was obtained. a-Morpholinylmethyl-@-naphthol (V lb) (0.24 g., 0.001 mole) was heated under reflux for two hours with piperidine (0.42 g., 0.005 mole). Water was added to the cooled solution, and the solid which precipitated was crystallized once from alcohol. Pure a-piperidinomethyl-8naphthol (V IC), 0.12 g . (500/0), m. p. 94-95", was so obtained. Similarly, a-piperidinomethyl-@-naphthol ( V IC) (0.24 g., 0.001 mole) was heated with morpholine (0.44 g., 0.005 mole). The product obtai:ed by addition of water to the solution melted a t 102-107 . A small amount of a;morpholinomethyl-B-naphthol (V l b ) , m. p. 116-117 , the
.
.
(20) Auwers and Dombrowski, Ann., 844, 280 (1908). (21) Shriner, Grillot and Teeters, THISJOURNAL., til, 946 (1946).
more soluble of the two Mannich bases, was obtained in pure state by fractional crystallization of the crude product from 50% ethanol. Betti Bases (V 2).-The method of "Organic Syntheses"e2 was used in the preparation of 1-a-aminobenzyl2-naphthol (V 2d). This material melted sharply a t 113114' (lit.2* 125') ; its melting point was not raised by seven recrystallizations from ether, nor by repeated crystallization from benzene-petroleum ether. The amine formed a hydrochloride, m. p. 190" (dec.), and a benzaldehyde condensation product, m. p. 144-145", both of which were identical with intermediates in the preparation.2P The acetamido derivative prepared from the amine by use of acetic anhydride and the product formed by condensation of benzaldehyde, @-naphtholand acetamide were identical and melted at 223-225' (lit. 236').2s Themethod of Littman and Brodez' was used in the preparation of l-adi; methylaminobenzyl-2-naphthol (V 2a), m. p. 163-164 (lit.24 164-165'), la-piperidinobenzyl-2aaphthol (V 2c), m. p. 198-199' (lit.2' 198-198.5"), aud l-cu-morpholinobenzyl-2-naphthol (V 2b). The last-named compound has not previously been prepared. A solution of morpholine (8.7 g., 0.1 mole), @-naphthol(14.4 g . , 0.1 mole) and benzaldehyde (10.6 g., 0.1 mole) in ethanol (12 ml.) was let stand for two days. The solid which separated was thrice crystallized from benzene-petroleum ether to yield 28.0 g. (88%)of coarse white crystals of V 2b, m. p. 176.5177.0". AnaZ.26 Calcd. for C21H21NOs: C, 78.97; H, 6.63; N, 4.39. Found: C, 78.89; H, 6.85; N, 4.30. Amine Exchange Reactions of Betti Bases (V 2).-A solution of la-aminobenzyl-2-naphthol (V 2d) (0.29 g., 0.001 mole) and morpholine (0.44 g., 0.005 mole) in xylene (2 ml.) was heated under reflux for four hours. When the evolution of ammonia had ceased, the solution was cooled and high-boiling petroleum ether (10 ml.) was added to it. 1-a-Morpholinobenzyl-2-naphthol (V 2b) crystallized slowly from the solution. There was obtai2ed 0.31 g. (87.5%) of the tertiary amine, m. p. 175-176 Similar results were obtained when l-a-dimethylaminobenzyl-2-naphthol (V 2a) was heated with morpholine in xylene. l-a-Piperidinobenzyl-2-naphthol (V 2c) was formed when either V 2d or V 2a was heated with piperidine in xylene.
.
Summary Ketonic and phenolic Mannich bases react with secondary amines by amine exchange. The process is reversible and occurs without appreciable side reactions. The mechanism of this reaction appears to be analogous to that of other amine replacement reactions of Mannich bases. URBANA, ILLINOIS
RECEIVED JULY 26, 1948
(22) Betti, "Organic Syntheses," Colt. Vol. I . 2nd ed., John Wiley and Sons, Inc., New York, N. Y.,1941, p. 303. (23) Betti, Cars. chim. i t d . , 881, 5 (1903). (24) Littman and Brode, THISJOURNAL, 68, 1655 (1930). (26) Microanalyses by Miss Emily Davis and Mr. Howard Clark.
