and gave 1.0 g. of benzophenone, 2,4-dinitrophenylhydrazone, m.p. 238" (reported'" 239") and 0.98 g. of p-benzoylbenzoic acid, m.p. 193-194" (reportedla 194'). F. a-(m-Tolyl)-benzoin.-A 5.0-g. sample of a-(m-tolyl)benzoin, h.p. 200-204" a t 0.65 mm. (reported' 210-240' at high vacuum), WAS cleaved by the procedure described above. A 2.0-g. portion of the neutral fraction (3.42 g.) was oxidized with chromic acid and gave 1.3 g . of benzophenone, 2,4-dinitrophenylhydrazone, m.p. 225226" alone or mixed with authentic derivative (reportedlo 239'), and 0.93 g. of m-benzpylbenzoic acid, n1.p. 163-164" (reported" The ether-extracted cleavage solutiori was 181-162'). acidified and the acid fraction was extracted with ether. Oxidation with chromic acid gave 1 . 1 g. of isophthalic acid, n1.p. 300' (reported'" :300n), aiicl 0 . 7 g. of 1)erlzoic acid, -. .-___ i l 4 ) IJ. SeuR. .Im., 220, 22,; ilSR.'!i
[ C O U ? R I B ~ T I O UFROM THE SCHOOL OF
m.p. 120-121' alone or mixed with authentic benzoic acid. G . a-(0-Tolyl)-benzoin.-A 1.28-g. sample of ~ ( 0 tolyl)-benzoin , m. p. 116.&117 (reported' 116-1 17o), was cleaved in the usual manner. The neutral fraction (0.73 g.) proved to be benzhydrol, m.p. 65-66' alone or mixed with authentic benzhydrol (reportedlo 68"). The acid fraction (0.50 g.) proved t o be o-toluic acid, m.p. 102-103° (reported'" 102'). A second cleavage of 2.0 g. of a-(0-tolyl)benzoin gave a neutral fraction which was oxidized with chromic acid and gave 1.1 g. of benzophenone, 2,4-dinitrophenylhydrazone, ri1.p. 234-240' alone or mixed with authentic derivative (reportedIo239'). No acid compound was found as an oxidation protiuct. The acid fraction (0.82 g.) from the cleavage was o-toluic acid, m.p. 100-101'' (reportedlo 102°). hf.ANIIATTA.U, K A Y S A S
CHEMISTRY OF THE UNIVERSITY O F MINNESOTA]
Studies of the Bicyclo [2,2,1] heptene-2 Ring System. I1 W I L L I ~ E. V P\RII4M, ~ ~ I I . I , I A M T. HUNTER, ROBERTA HhNSON AND THOMAS LAHR RECEIVED APRIL 16, 1932 The reaction of endo-5-aminobicyclo [2.2,1]heptene-2 with formaldehyde and formic acid gives the corresponding ketone (24%) as well as the expected tertiary amine (30%) and trimethylamine The formation of the ketone has been attributed heptane, to steric factors and not participation of the double bond, since the saturated amine, endo-5-aminobicycl0[2.2,1] behaves similarly. Methylation of d-( &phenylisopropyl)-amine by the Clarke procedure resulted in no racemization, thus intermediates of the type RpC=K--CHs are not involved. M'hen the quaternary base of endo-5-dimethylarnino[2.2,1] heptene-2 was pyrolyzed, the amine was regenerated. Other reactions are cited which indicate t h a t bicyclo[2,2,1]2,5, heptadiene is not easily formed by elimination reactions involving the bicyclo[2,2,1]heptene-2 ring system.
During a previous study of compounds' con- depress the melting points of the corresponding taining the bicyclo-(2,2,l)-heptene-2ring system, derivatives prepared from an authentic sample of one of us observed that the action of formaldehyde VI. The reduction of nortricyclanone under and formic acid on endo-S-aminobicyclo-(2,2,1)- conditions used for the reduction of I1 did not heptene-2 (I) resulted in 24% yield of ketonic result in the formation of VI by hydrogenolysis; material, a 30yo yield of a tertiary amine and an consequently, nortricyclanone cannot be present undetermined quantity of trimethylamine. The in large amounts as an impurity in 11. The infrared spectrum of 111 revealed no broad absorption band near 800 cm.-l, indicating2 the absence of the nortricyclane ring structure. When I11 was reduced (Pt, Hz), 90% of one mole of hydrogen was absorbed and the product was " 2 0 N(Ct'3h endo-2-dimethylarnino-(2,2,1)-heptane (VII). I I1 111 I\' The reaction of endo-2-aminobicyclo-(2,2,1)quaternary hydroxide derived from the tertiary heptane (V) with formaldehyde and formic acid amine (111) did not give the expected products was investigated in order to ascertain whether or when subjected to the Hofmann degradation (tri- not the formation of ketones during the methylamethylamine and IV), but decomposed to give the tion of I could be attributed to participation of the original amine I11 and a volatile alcohol (presum- carbon-carbon double bond. The products of the ably methanol). The results of the methylation reaction were: 2-ketobicyclo-(2,2,l)-heptane(VI, reaction and the Hofmann degradation reaction were both unexpected; therefore, these reactions have been reinvestigated and additional evidence concerning the structures of the resulting compounds has been obtained. 0 The unstable ketonic product I1 gave a 2,4V VI VI1 dinitrophenylhydrazone and a semicarbazone which 40% yield) , endo-2-dimethylaminobicyclo(2,2,1) were difficult to purify by crystallization. The (VII, 27% yield) and trimethylamine. ketonic product was shown to be principally 5- heptane The formation of carbonyl compounds during the ketobicyclo-(2,2,1)-heptene-2 (11) by reduction methylation of amines with formaldehyde and (0.925 double bond) to the known 2-ketobicyclo- formic acid has been explained as outlined in the (2,2,l)-heptane (VI). The reduced ketone (VI) following equation.3 was isolated as its 2,4-dinitrophenylhydrazoneand (2) J. D. Roberts, E. R Trumbull, W. Bennett and R. Armstrong, its semicarbazone. These derivatives did not ibid., 71, 3117 (1960). " 2
( 1 ) W.E. Parham, 73, 5068 (1951).
W T.H u o t r r dud R. Hansou,
?'HIS
JOURNAL,
(3) fT T. Clarke, H. B. Gillespie and S.Z. Weishaus, i b i d . , 66, 4571 (1033).
Nov. 20, 1052
STUDIES OF THE BICYCLO [2,2,1]IIEPTENE-2
RINGSYSTEM
5647
[2,2,l]heptane (VI) by its conversion into thc 2,4dinitrophenylhydrazone and semicarbazone of VI. 2,4-Dinitrophenylhydrazoneof VI was prepared from the I I reduction product of I1 and recrystallized from ethanol, R' R' m.p. 130-131'. VI11 IX Anal. Calcd. for CLIHIIN~OI:C, 53.79; H, 4.86. A study employing d- (P-phenylisopropy1)-amine Found: C, 53.89; H , 5.19. The m.p. and mixed m.p. of the 2,4-dinitrophenylhydra(X) showed that no racemization occurred during prepared from an authentic sample of VI4 was 130methylation, thus establishing that intermediates zone 131". of type IX are not involved during the normal Semicarbazune of VI was prepared from the reduction Clarke methylation reaction. product of 11 and recrystallized from methanol and toluene. This product decomposed CH20 CHaI when heated t o 189-192° CsHs-CHrCH-CH3 ___ --f CBH~CII~-CH-CH~ -+ C6Hb-CH2-CH-CHs with Dreliminarv II HCOOH I I at 182' (repoked4 m . 6 "1 CHI-N-CHI tN(CH8)a 196.5-197.5'). X XI 1Anal. Calcd. for CsHlsXI1 ( C Y ) ~ ~-4.8" D ONa: C, 57.46; H , 7.83. CHaI Found: C, 57.46; H, 7.74, A sample of the semicarhazone prepared from an auThe failure of I11 to give bicyclo-(2,2,1)-2,3sample of VI melted at 189-192' with decomposiheptadiene (IV) under the conditions of the Hof- thentic tion and preliminary softening. A mixed melting point of mann reaction is evidence that this olefin is not the two derivatives melted at 189-192" (dec.). formed easily. Other evidence has been accumuNortricyclanone .2--The semicarbazone of nortricyclanonc lated to substantiate this conclusion. The Kraft was recrystallized from aqueous ethanol; m.p. 214-217" pyrolysis of bicycIo-(2,2,1)-2-heptene-5-acetate (dec. ) . Calcd. for CsH1lONa: C, 58.23; H , 6.67. Found: (XIIIa) gave cyclopentadiene, acetylene and acetic C,Anal. 58.50; H , 7.13. acid. The Tschugaeff degradation of bicycloReduction of Nortricyc1anone.-A sample of the ketone, (2,2,1)-2-heptene-5-01 (XIIIb) gave a small amount obtained by hydrolysis of its semicarbazone, was reduced using prereduced platinum oxide catalyst. The hydrogen absorbed amounted to 119% of that calculated t o reduce one double bond. Reduction of the carbonyl group must have occurred for the product gave a single 2,4-dinitrophenylhydrazone (m.p. 187.5-188.5') which was identified hy mixed melting point determination to be that derived 0-R from the starting ketone.2 S I I I a ( R = -C--CIla), S I I I b (K = -C S C H p ) The Amine 111.-A sample, b.p. 47' ( 5 i n i n . ) had the il II following composition. Calcd. for CgH15N: C , 78.80; H, 0 s 10.9. Found: C , 78.50; H , 11.3. 1. The picrate of I11 was recrystallized from ethanol; (5%) of low boiling illaterial which reacted with 190-195' (dec.) with preliminary darkening at 164'. phenylazide to give a product having the composi- 111.1). '??tal. Calcd. for ClsHlsN407: -C, 49.18;- H, 4.95. tion of one mole of IV plus two of phenylazide. Found: C, 49.31; H , 5.10. 2. The methiodide of I11 was recrystallized from ethanolExperimental petroleum ether (b.p. 90-100'); m.p. 160" (dec.). Anal. Calcd. for C ." I~H ."M N IC: . 43.02: H . 6.50. Found: Reaction of I with Formaldehyde and Formic Acid.-A C, 43.07; H, 6.37. mixture of amine (20 g., 0.2 mole), 87% formic acid (53 g., 3. Hvdronenation of I11 was effected in ethanol usiiie 1 mole) and 40% formalin (32 g., 0.4 mole) was heated a t prereduced g a t i n u m oxide catalyst. The hydrogen ab: the reflux temperature for seven hours. The resulting solution was treated with concentrated hydrochloric acid sorbed amounted to 90% of that required to reduce onc (16 ml., 0.2 mole) and distilled with steam. The distillate douhle bond. The ethanol solution was Concentrated and (100 ml.) was neutralized with sodium carbonate, saturated used to prepare the following derivatives. The picrate of endo-2-dimethylaminobicyclo-(2,2,1)-hepi with sodium chloride, and extracted with ether. The ketonic material I1 (5.2 g., 24%) was obtained from the tane (VII) was crystallized from ethanol; r11.p. 213-216 (dec. ) . ethereal solution as a colorless oil. Anal. Calcd. for CliH2007~4: C, 48.91; € I , 5.44. The acidic residue from the steam distillate was made strongly alkaline with sodium hydroxide and the amine was Found: C, 49.21; H, 5.63. extracted with ether. During the neutralization a gaseous A mixture of this picrate and that obtaiiied from 1-11, amine separated which was identified as trimethylamine by which was prepared from V (see below), melted a t 213-216' the conversion of this compound to the picrate (m.p. and (dec. ). mixed m.p. 215-219" dec.). The tertiary amine I11 (7.4 The methiodide of cndo-2-dimethylaminobicyclo(2,2,1)g., 30%) was obtained from the ether extract by distillation heptane (VII) was recrystallized from ethanol; m . p . 291.(b.p. 167-175"). 293". Product 11. 1 .-The 2,4-diiiitrophenylhydrazone (m.p. Anal. Calctl. for CloHz0SI:C , 42.70; H , 7.12. Fouiitl: 133-137') could not be obtained pure by crystallization. C , 42.62; H , 7.26. A sample melting at 149-154" after repeated crystdllizaA mixture of this methiodide and that obtained from endotion from ethanol had the following composition. dimethylaminohicyclo-(2,2,l)-heptanc which was derived .4nal. Calcd. for C&&N4: C, 54.16; IT, 4.03; S , from V (see below) melted at 292" dec. The X-ray diffrac19.44. Found: C, 54.04; H , 4.62; iY,19.46. tion pattern of these two methiodides were identical.6 Reaction of V with Formaldehyde and Formic Acid.-The 2. The semicarbazone (m.p. 197-203' dec.) could not be obtained pure by crystallization. A sample melting a t amine VB(7.2 g . ) was treated with formaldehyde and formic acid by a procedure similar to that descrihed for I . 197-203' dec. had the following composition. Anal. Calcd. for CaHlION3: C, 58.16; H , 6.71; S , (4) 0 Diels and K. Alder, An?t , 470, 76 (lQZ9). 25.44. Found: C, 58.28; H , 7.33; N, 25.00. (.5) The authors would like to thank Dr. W. N. Lipscnmh. Univer3. Hydrogenation of I1 was effected in alcohol using pre- sity of Minnesota, for the X-ray diffraction analysis. The sample5 reduced platinum as a catalyst. The hydrogen absorbed were run as powders using a General Electric XRD-3unit with Geiger corresponded to 92.7% of t h a t calculated to saturate one counter recording. dpuble bond. The product was identified as 2-ketobicyclo(6) K. Alder and G.Stein, A n n . , 614, 224 (f931). RCH-N=CH*
H2O + ketone
IfR-C=N-CIIJ
L
f
~
T h e ketonic fraction (4 g., 40%) was shown t o be 2-ketobicyclo-(2,2,1)-heptane (VI) by its conversion into the 2,4dinitrophenylhydrazone of VI; m.p. and mixed m.p. with an authentic sample was 130-131'. The tertiary amine VI1 ( 3 g., 27% yield) was distilled; b.p. 165-180". Anal. Calcd. for CsH~7X:C, 77.71; H , 12.2. Found: C, 78.21; H, 12.3. The methiodide of this amine melted a t 292" with decomposition. The identity of this product t o that obtained by the reduction of I11 has already been noted. The Hofmann Degradation of the Methiodide of endo-5Dimethylaminobicyclo-(2,2,1)-heptene-2(III).-A solution of the methiodide (5.4 g.) in 100 ml. of 15% potassium hydroxide was distilled in an atmosphere of nitrogen. The exhaust gases were passed through a solution of picric acid. Decomposition occurred when about 85 ml. of water had distilled; however, no trimethylamine was formed. T h e picrate of the product melted a t 190-194" (dec.) and a mixed melting point of this picrate with a n authentic sample of the picrate of endo-5-dimethylaminobicyclo-( 2,2,1)-heptene3 (111), m.p. 190-195' (dec.), was 190-194". A solution of the methiodide (21 9.) in methanol (300 inl.) was treated with silver oxide (9.25 g.), and the solution of methohydroxide was distilled a t atmospheric pressure. The residue decomposed a t 100-180'; however, no trimethylamine was observed. The product was 111. Methylation of &dimethyl-( &phenylisopropyl)-amine ( X ) with formaldehyde and formic acid gave &dimethyl-( phenylisopropyl)-amine ( X I ) , b.p. 68-72' (2.5 mm.), 66% yicld, [ L Y ] ~ f5.11' ~D (absolute ethanol). Anal. Calcd. for C11H17N: C, 80.92; H, 10.50; S , 8.68. Found: C, 81.06; H, 10.59; K, 8.78. Conversion of XI to XI1 was effected by reaction of X I with methyl iodide in ether. The product was recrystallized from ethanol; m.p. 196--197", [ c Y ] * -4.81" ~D (distilled Hzo).
-
a-
!COSTRIBLTION FROM
THE ~ I V I S I O XOF P U R E
Anal. Calcd. for C I ~ H ~ O XC,I : 47.2; H , 6.56. Found: C, 47.6; H , 6.98. Methylation of d-( a-Phenylisopropyl)-amine with Methyl Iodide.-A mixture of 250 ml. of water, 25 g. of sodium carbonate, 11.2 g. of X and 30 g. of methyl iodide was heated a t the reflux temperature for nine hours. The reaction mixture was cooled and the crystals filtered, washed with ether, and dried. The product weighed 18.2 g. (72% yield) and was the methiodide of XI. A sample of the product was recrystallized from ethanol. The m.p. and mixed m.p. with the product described in the preceding experiment was 196197'; [ Y ] ~ ~-4.83' D (distilled H20). The decomposition of bicyclo-(2,2,1)-2-heptene-5 acetate' was carried out by allowing the ester t o pass (25 g./hr.l through a hot tube (580") in an atmosphere of nitrogen. A material balance was not obtained; however, the following products were isolated: ( a ) acetylene (in exhaust gas), ( b ) acetic acid, (c) cyclopentadiene (n1.p. and mixed m.p. of dibromo derivativea was 4546') and (d) vinyl acetate. The Decomposition of the Methyl Xanthogenate of endo5-Hydroxybicyclo-(2,2,1)-heptene-2 (XIIb).-The crude xa~ithogeiiate~ (b.p. 120-126" (10 m m . ) ) was decomposed a t 250' in an atmosphere of nitrogen. A small amount of volatile oil (ca. 5%) boiling a t 40-70' was obtained. This product reacted with phenylazide in ether t o give a crystalline product (dec. 200') which was insoluble in ether, benzene, alcohol and chloroform. The light tan needles werc washed with alcohol and ether. ,1nal. Calcd. for CigHia06: C, 69.08; H, 5.49. Found: C, 69.03; H, 5.81. 17) K. Alder and H. Rickert, ibid., 643, 15 (1939). (8) E. Farmer and W. Scott, J. Chem. Soc., 177 (1029). (9) Whitmore and Simpson, THISJOURNAL, 55, 3809 (1933j.
MINXEAPOLIS 14, MINXESOTA
CHEMISTRY
OF
THEN A r I O S A L KESEARCH COUNCIL
OF
CANADA]
The Characterization of Methyl and Methylene Groups in Steroids by Infrared Spectrometry. I. Correlations of Bending Frequencies with Molecular Structure' BY R . NORMAN JONES
AND
A. R. H. COLE^
RECEIVED APRIL11, 1952 The major absorption bands between 1360 and 1500 cm.-' in the spectra of steroids can be assigned to vibrations of inethyl and methylene groups in the molecule. These vibrations appear to be localized in individual methyl and methylene groups, and the following correlations between molecular structure and infrared spectra have been established for this region of the spectrum. ( a ) The cyclic methylene groups of the steroid ring system absorb a t a different frequency from the linear methylene groups in the side chain. (b) Methylene groups adjacent t o carbonyl groups and t o ethylenic linkages absorb a t characteristic positions. In steroids containing the group -CHz-CO- the frequency of the a-methylene bending vibrations is determined by the location of the carbonyl group and serves t o supplement the C=O stretching frequency for the characterization of the carbonyl position. ( c ) The angular methyl groups, the terminal side chain methyl groups, and the methyl group in the acetoxy radical of steroid acetates, absorb a t different positions and can be distinguished. The band positions associated with these various types of methyl and methylene groups are listed in tables, and examples are given t o illustrate the application of these correlations t o the elucidation of molecular structure.
The infrared absorption bands of large organic molecules may be classified into three principal types; (i) a relatively small number of bands due to stretching vibrations of specific groups, notably 0-H, C-H, C=O, and C=C in the higher frequency region (1575-3650 ern.-'); (ii) C-H bending bands of methyl and methylene groups between 1350 and 1500 cm.-'; (iii) a complicated pattern of overlapping bands due to skeletal stretching vibrations and C-H deformation vibrations below 1350 cm.-I. The latter absorption is most sensible to small changes in molecular structure and
has been aptly described as the "fingerprint" region. An extensive study of the bands due to specific 0-H, C=O and C=C stretching vibrations in steroids has enabled a set of correlations to be established between band position and molecular and these correlations have proved useful in determining the structure of newly isolated steroids. From studies of the infrared spectra of simple ali-
(1) Presented, in part, a t a Symposium on Molecular Spectroscopy held a t the Ohio S t a t e University, Columbus, Ohio, June, 1950, and published as Contribution No. 2857 from the Laboratories iuf T h e S a t i o n a l Research Council of Canada. ( 2 ) National Research' Council Postdoctorate Fellow.
JOUREAI.,
(3) R. N. Joues and K. Dobriner, Vitamiits aitd Hormoses, 7 , 293 (1949). (4) R . N. Jones, P. Humphries, E . Packard and K D o b r i n c r , THZS
71, 2 1 1 (1949). I
