NEREOCHEMICAL HUDIES 0F SCREW BA$E$ rY NUCLEAR MGNEIIC RESQNAMCE WCFROSSCOPY {hula for “10 Degree: 0‘ DI» D- MICHIGAN STATEUNIVERSITY Shefldmm Sifimey Lahde ' 1966 ' THESlS This is to certify that the thesis entitled STEREOCHEMICAL STUDIES OF SCHIFF BASES BY NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY presented by Sheldon Sidney Lande has been accepted towards fulfillment of the requirements for Ph . D . degree in Chemi stry E f/(MJ Jig Major professor Dme October 19, 1966 0-169 ABSTRACT STEREOCHEMICAL STUDIES OF SCHIFF BASES BY NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY by Sheldon Sidney Lande N-Methyl ketimines were found to exist as syn (13) and anti (12) isomers; syn/anti ratios of 86/14, 97/5, and 100/0 CH3 CH3 / N \N H H C c \ R/ CH3 R/ \CH3 £51 1b were found for R = ethyl, isopropyl, and t—butyl, reSpectively. orMethyl protons appeared further upfield when gig than when Eggng to the N-methyl group by 0.13 p.p.m. in carbon tetra- chloride solution and from 0.45 to 0.57 p.p.m. when in benzene solution. While their resonances apparently overlapped in carbon tetrachloride solution, in benzene solution gig— oemethylene protons and gig—B-methyl protons resonated 0.15 p-pom- and from 0.20 to 0.54 p.p.m., reSpectively, at higher magnetic fields than the corresponding trans—protons. N—Alkyl aldimines were found to exist in only the syn configuration,.§. Sheldon Sidney Lande 2 R2 CH3 /’ N// N H H C C Rf \H R/ g E The larger AV values (Vin benzene — Vin carbon tetra- chloride) for 0% and B-protons gig to the N-methyl group of 'N-methyl ketimines than for the corresponding trans—protons were interpreted in terms of Specific interaction between benzene and ketimine as shown in g. The Av values fOr the aldimines suggested a similar solvation model. Three types of spin-spin coupling were studied in N-alkyl aldimines {4): vicinal coupling between H1 and Haw four-bond coupling between H1 and HN, and five-bond coupling between Ho and HN' Protonation of the N—methyl aldimines washed out the long—range couplings. N//C\HN H c \\ T/ H HQ 4 The stereochemistry about the bond joining the tetra- hedral and trigonal carbon atoms of N-methyl aldimines was studied by means of the vicinal coupling. Differences in the vicinal coupling constants with changes in temperature and Sheldon Sidney Lande solvent polarity were interpreted in terms of rotamers 5 and.§. N//CH3 N/CH3 H R \1/LLH fi/‘LH / / R H Im lm Free energy and enthalpy differences between the two rotamers were calculated for the individual aldimines. The eclipsed rotamer, g, was favored over 5 for Nemethyl propionaldimine by an enthalpy difference of 100 cal./mole. The enthalpy dif- ference for rotamers_§ and g was found to be zero for N-methyl butyraldimine, heptylaldimine, and cyclohexanecarboxaldimine. For all other aldimines, rotamer 5 was favored over g by an amount that increased as the size of the R group increased. The stereochemistry about the bond joining the tetrahedral carbon and trigonal nitrogen in N-alkyl acetaldimines was studied by means of the long-range couplings. Their relative insensitivity to temperature and to the size of the groups replacing the N—methyl protons was interpreted in terms of the greater stability of.1 over_§. H\\ //CH3 H STEREOCHEMICAL STUDIES OF SCHIFF BASES BY NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY BY Sheldon Sidney Lande A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Chemistry 1966 / I ‘ x , . 2 -_/ 1"” K I. :1 :1/ f ’ - "C ‘ ’7', /~;./. . ~J Donna Rita To my wife, ii ACKNOWLEDGEMENTS The author expresses his thanks to Dr. G. J. Karabatsos for the guidance and inspiration which he provided during the course of this work. He also expresses his appreciation to his mother for her financial assistance during the years of his education. Gratitude is extended to the United States Atomic Energy Commission for financial support during part of this work. iii TABLE OF CONTENTS Page INTRODUCTION . . . . . . . . . . . . . . . . . . . . 1 1. Configurations . . . . . . . . . . . . . . . 1 2. Conformations. . . . . . . . . . . . . . . . 6 RESULTS. . . . . . . . . . . . . . . . . . . . . . . 10 1. Chemical Shifts and Configurations of Ketimines. . . . . . . . . . . . . . . . . . 10 2. Effect of Solvent on the Chemical Shifts of N-Methyl Ketimines . . . . . . . . . . . . . 16 3. Chemical Shifts and Configurations of Aldimines. . . . . . . . . . . . . . . . . . 16 4. Effect of Solvent on the Chemical Shifts of Aldimines. . . . . . . . . . . . . . . . . . 50 5. Vicinal Spin-Spin Coupling Constants of Aldimines: Conformations Along the Bond Joining Tetrahedral Carbon to Trigonal Carbon . . . . . . . . . . . . . . . . . . . 50 6. Long-range Spin-spin Coupling Constants of Aldimines: Conformations Along the Bond Joining Tetrahedral Carbon to Trigonal Nitrogen . . . . . . . . . . . . . . . . . . 49 7. Long-range Spin—Spin Coupling Constants of N-Methyl Ketimines . . . . . . . . . . . . . 56 8. Effect of Acid on the Nuclear Magnetic Resonance Spectra of Aldimines . . . . . . . 60 DISCUSSION . . . . . . . . . . . . . . . . . . . . . 66 1. Configurations . . . . . . . . . . . . . . . 66 iv TABLE OF C ONTENTS - Continued 2. Interaction with Benzene . 5. Conformations. . . . . . . EXPERIMENTAL . . . . . . . . . . . 1. Reagents . . . . . . . . . 2. Preparation of Schiff Bases. 5. Attempted Preparation of N-Methyl Form— al N-methyl acetaldimine. . N—methyl cyclohexanecarboxaldimine N-methyl valeraldimine . Nit-octyl propionaldimine. N-propyl acetaldimine. . N-methyl ethyl methyl ketimine Attempted preparations of N— t- -octyl di— methyl ketimine. . . . dimine O O O O O O O O O 4. Nuclear Magnetic Resonance Spectra . 5. Solvents . . . . . . . . . 6. Attempted Isomerization of N-Methyl Acet- aldimine . . . . . . . . . REFERENCES . . . . . . . . . . . . Page 69 70 75 75 74 74 77 77 77 77 78 78 79 80 80 81 85 TABLE II. III. IV. VI. VII. VIII. IX. XI. XII. XIII. LIST OF TABLES Chemical Shifts (T—Values) of N—Methyl Ketimines in p.p.m. . . . . . . . . . . . . . A6(6 is) for N-Methyl Ketimines. . . trans Isomer Distribution, Ke , and AG0 for N-Methyl Ketimines . . . . . . .q. . . . . . . . . . . Comparison of Chemical Shifts of N-Methyl Ketimines in Benzene and Carbon Tetrachloride Chemical Shifts (T—Values) of N—Methyl Aldimines . . . . . . . . . . . . . . . . . . Comparison of the Chemical Shifts (T-Values) and Spin-Spin Coupling Constants (JH H ) in c.p.s. for N-Methyl and NfiE-Octyl l a Aldimines . . . . . . . . . . . . . . . . . . Chemical Shifts (T-Values) for N—Alkyl Acetal- dimines in p.p.m. . . . . . . . . . . . . . . Models for Calculating 1,6-Proton, Proton Repulsions in cis-Butene-Z and anti-NrMethyl Acetaldimine. . . . . . . . . . . . . . . . . Calculated Non—bonded Repulsion Energies. . . Comparison of Chemical Shifts of N-Methyl Aldimines in Benzene and Carbon Tetrachloride Vicinal Spin-Spin Coupling Constants of N—Methyl Aldimines. . . . . . . . . . . . . . Long—range Spin—Spin Coupling Constants of N-Methyl Aldimines. . . . . . . . . . . . . . Effect of Solvent on Vicinal and Long- range Spin— Spin Coupling Constants of N-Methyl Aldimines . . . . . . . . . . . . . . vi Page 11 14 15 17 19 24 28 29 51 55 55 57 LIST OF TABLES - Continued TABLE XIV. XVII. XVIII. XIX. XXI. XXII. XXIII. XXIV. XXVI. XXVII. XXVIII. XXIX. Relative Populations of N-Methyl Aldimine Rotamers. . . . . . . . . . . . . . . . . . . Solvent Effect on the Relative Populations of N-Methyl Aldimines. . . . . . . . . . . . . . AGO of N-Methyl Aldimine Rotamers . . . . . Effect of Solvent on AGO of N-Methyl Aldimine Rotamers. . . . . . . . . . . . . . . . . . . AHO for Rotamers of N-Methyl Aldimines. . . . Vicinal Spin-spin Coupling Constants for NéAlkyl Acetaldimines . . . . . . . . . . . . Long-range Spin-Spin Coupling Constants for N-Alkyl Acetaldimines . . . . . . . . . . . . Parameters Used in Calculating Repulsions Between H1 and H5 of N-Ethyl Acetaldimine and Butane-1. . . . . . . . . . . . . . . . . . . Long—range Spin—Spin Coupling Constants for N-Methyl Ketimines. . . . . . . . . . . . . . Effect of Temperature on the Long—Range Spin- spin Coupling Constants of N—Methyl Ketimines Comparison of Long-range Spin-Spin Coupling Constants Between trans—0+ and N—Methyl Protons of Aldehyde and Ketone Methylimines Effect of Acid on the N.M.R. Spectra of Aldimines . . . . . . . . . . . . . . . . . Boiling Points of N-Methyl Aldimines. . . . . Boiling Points of Neg-Octyl Aldimines . . . Boiling Points of N—Alkyl Acetaldimines . . Boiling Points of N-Methyl Ketimines. . . . vii Page 40 41 45 46 47 50 51 58 59 59 62 65 75 75 76 76 LIST OF FIGURES FIGURE 1. N.m.r. spectrum of N-methyl ethyl methyl ketimine taken as the neat liquid. . . . . . . 2. Effect of benzene dilution on the chemical shift of N-methyl ethyl methyl ketimine. . . 5. Spectra of N-methyl osethylhexylaldimine and Nat-octyl osethylhexylaldimine taken as the neat liquids . . . . . . . . . . . . . . . . 4. N.m.r. spectrum of N—iSOpropyl acetaldimine taken as the neat liquid . . . . . . . . . 5. Effect of benzene dilution on the chemical shifts of Nit-octyl acetaldimine . . . . . . . 6. Partial n.m.r. spectrum of N-methyl deethyl- hexylaldimine taken as the neat liquid . . . . 7. Vicinal coupling, JH Hg! for i—C3H7CH2CH=NCH3; C3H5CH2CH=NCH3; _r_1_-c 5H11CH2CH=NCH3§ CH3CH2CH= NCH3.1§. temperature . . . . . . . . . . . . . 8. Logic K Kg. 1/T for oemethylbutyraldehyde methylimine. . . . . . . . . . . . . . . . 9. Partial n.m.r. spec rum of N-ethyl acetal- dimine taken at +20 C. as the neat liquid. . . 10. 1,6-Proton—proton repulsion energies for N- ethyl acetaldimine and butene-1 X§.conformation 11. Partial n.m.r. spectrum of N-methyl ethyl methyl ketimine taken of the neat liquid . . . 12. H1 resonance of N-methyl butyraldimine as 5% (m./m.) solution in acetonitrile before and after addition of three drops of trifluoro— acetic acid. . . . . . . . . . . . . . . . viii Page 15 18 25 25 52 56 45 48 52 61 64 INTRODUCTION 1. Configurations Restricted rotation about the carbon—nitrogen double bonds of Schiff bases results in configurational isomerism. Until the advent of nuclear magnetic resonance Spectroscopy, study of this stereoisomerism was confined to derivatives of ring-substituted benzaldehydes and unsymmetrical benzo- phenones where isomers could be identified by differences in the infrared and ultraviolet Spectra. Nuclear magnetic resonance Spectroscopy now permits clear identification of the isomers of Schiff bases derived from aliphatic aldehydes and ketones; in addition to the configurations of Schiff bases, it has been used for studying analogous systems includ- ing nitrosamines, substituted hydrazones, oximes, and carba— mates (1). This work deals with the configurations of simple, non-conjugated Schiff bases. Though benzaldehyde anils normally exist in the syn— configurations (syg_defined as the isomer in which the alde— hydic proton is gig to the N-substituent), the anEi—config— urations have been obtained photolytically. When early workers (2,5,4) observed some anils in two forms of different color and melting point, which interconverted on either heating or irradiating, they mistakenly reported that these forms were configurational isomers. But, Gaock and LeFevre (5), using dipole moment arguments to deduce configurations, reinvesti- gated these assignments and established that the two forms were actually crystalline modifications of the syn-configur— ations. Fischer and Frei (6,7) first succeeded in preparing the antifisomers oflg (R1 = R2 = hydrogen), 2a, and 2b by irradiating the syn-isomers in methylcyclohexanefigepentane R2 ' D 00 N ll 0 I! C I C\\\ 1 2 H (a)R=H (b) R=0H at -1000C. They ascertained that these were the apt}; isomers by the similarities of the ultraviolet Spectra of the two forms of the Schiff bases to the analogous oxime isomers. Wettermark and his co-workers (8,9,10) generated the anti: forms of several anils of type 1_by flash photolyzing the gynf forms at 500C. The anEi-isomers, which rapidly collapsed to the sygfisomers (half-lives of approximately 0.5 sec.), were again identified by their ultraviolet Spectra. So far, studies of Schiff bases derived from aldehydes and alkylamines have disclosed only the gygfconfigurations. When Curtin and his co—workers (11) examined the n.m.r. Spectra of the methylamine derivatives of p—substituted benzaldehydes, .5, they observed resonances of the N-methyl and aldehydic H C6H5 \ \ I /C C'\ H N c\ H H H c c (CH3) 2CH/ \H H/ \CH(CH3) 2 R 4 H /CH3 C6H5\ I I04 protons characteristic of one isomer, which they presumed had the syn-configuration. Likewise, from the n.m.r. spectrum of the double aldimine 4_Staab, Végtle, and Mannschreck (12,15) elicited the presence of only one isomer, to which they assigned the syn-configuration on a steric basis. For their study of N-butyl butyraldimine and N-butyl isobutyraldimine, Hires and Balog (14) decided that the presence of one ultra- violet absorption band furnished sufficient evidence to assign them exclusive gynfconfigurations. Both configurations of ketimines derived from unsymr metrical benzophenones have been found to be present at room temperatures. The isomers of N-alkyl ketimines possessed sufficient stability to permit their isolation. While Bell, Conklin, and Childress (15,16) and Saucy and Sternback (17) isolated both isomers for ketimines of type 5, Curtin e; l. .— (11,18,19) isolated 63 and_§b. The stereochemistry of the isomers was resolved by means of ultraviolet and infrared EHgRZ /CH3 N N RHN H where H c c ONO (WWW R1 R1 \ ‘\\/’\ R2 .§ §. R1 R2 (a) Cl H (b) H N02 Spectroscopy. Although benzophenone anils equilibrated too rapidly to permit isolating the individual isomers, Curtin, §£_§l. (11,18) detected two n.m.r. resonances for the pftoluidine methyl protons in anils of type 13 and for the pemethoxy protons in anils of type 1p. Nuclear magnetic resonance Spectroscopy has been used extensively in studies of ketimines containing or and 8- protons or fluorines. Andreas (20) elicited the rate of inversion of the isopropyl group about the carbon-nitrogen double bond of perfluoro—N—isopropyl dimethyl ketimine by following the coallescence of the drmethyl fluorine resonances with increasing temperature. Curtin gt 1. (11) and Staab _et 1. (12,15) analyzed the configurations of ketimines of types 8 and g by means of the dimethyl proton peaks; the ceH‘.3 H H ceH5 \/ \l c c N a a H H N / \ H R CH3 c c CH3/ \R R/ \CH3 .§ .2 Spectra of the acetone imines proved that n.m.r. differen- tiated between ormethyl protons gig and trans to the N- substituent. While one armethyl resonance appeared in the spectra of both types of pinacolin and 5—methylbutanone imines, which demonstrated that only one configuration was present, two types of oemethyl protons occurred in both types of butanone imines (in a 4:1 ratio in both), which proved that both configurations were present. The two groups of workers assigned the gyneconfiguration to the dominant isomers on the basis that it has less severe steric repulsions than the antifconfiguration (syn defined as the isomer in which the armethyl is gig to the N-Substituent). Because of the complexity of its spectrum, Stabb §;__l, (12) were unable to differentiate between the gig: and trans—armethylene pro- tons of 19; but, they could differentiate between the cis— C5H5 H H C6H5 \J \c, N/ \N II II c c CHgCHg/ \CHZCHg CH3CH2/ \CH2CH3 10 and trans-B-methyl protons. From the n.m.r. spectra of the methylamine derivatives of the alkyl phenyl ketones 11a-c Roberts EE._l~ (21) concluded that the only isomer present was that in which the aromatic ring was situated trans to the N-methyl. // (a) R::sec-C4H9 H (b) R=C2H5 c \ Q/ R (c) R=r_1_-c3H—, 2. Conformations Interpretations of molecular spectra, dipole moments, and electron diffraction spectra of olefins and carbonyl containing compounds (25—55) have established that the minimum energy conformation along the bond joining tetrahedral and trigonal carbons is 12a, where an a—substituent eclipses the trigonal atom, rather than the previously assumed (22) staggered arrangement 12b. Because spin-spin couplings depend upon the dihedral angles between the interacting protons 12a 12b —_ _— (54,55), n.m.r. has provided an excellent tool for studying conformational changes in such systems. These studies have utilized both vicinal spin-Spin couplings, 153, which exhibit maxima at dihedral angles, 9, of OO and 1800 and minima at 900 and 2700, and long-range spin-spin couplings that transverse double bonds, 15p, which exhibit maxima at dihedral angles, D, of 900 and 2700 and minima at 00 and 1800. 7i [.1 H‘ ‘fi—H 0(\ 9 (2f - C C C 15a 15b Both types of Spin—spin couplings have been employed in studies of olefins. Whipple and co-workers (28,29) correlated a trend toward smaller 1,5-Spin-Spin coupling constants for 2,5-dihalopropenes with increasing solvent polarity to increases in the populations of the more polar rotamers, 14b and 9. Using the vicinal spin—spin couplings H H H H H / \ x \c H c/ H I H /HY X/HY H /% Y H H X :3 lo. 2, 8 between the oemethylene and methine protons, BothnereBy and his co—workers (56-58) estimated the rotamer populations of several 5-Substituted propenes, 14 (Y = hydrogen). Their work disclosed that methyl eclipsing of the methylene, 14; (Y = hydrogen and X = methyl), in butene-1 was statistically equivalent to proton eclipsing,.;éb_or g, at 560C. They also found that the amount of substituent eclipsing decreased as the size of the group X increased. For example, for primary olefins (X = alkyl group) the amount of alkyl eclips- ing followed the order methyl > iggfpropyl > peggebutyl and for allyl halides (X = halogen) the order chloro > bromo > iodo. To explain marked increases in the vicinal coupling of the aldehydic and armethylene protons of prOpionaldehyde with increasing temperature, Abraham and Pople (40) postulated that methyl eclipsing of the carbonyl oxygen was statistically preferred to proton eclipsing. Karabatsos and Hsi (41) further explored the conformations of aliphatic aldehydes. They found a thermodynamic preference for alkyl eclipsing (except when the alkyl group was tfbutyl), géafl over proton eclipsing, 15b or gj for aldehydes containing two drprotons R R1 0 H O x H \ H H/H R/,}/M\H Rl/H R; H .3 E. (R1 = hydrogen). Besides observing that the preference for alkyl eclipsing declined when the size of the alkyl group was increased, they found that replacing a second orproton with an alkyl group decreased the thermodynamic preference for alkyl eclipsing. So, while ethyl eclipsing is preferred over proton eclipsing in butyraldehyde, proton eclipsing is favored over ethyl in urethyl butyraldehyde. The present work describes the conformational analysis about the bond between the tetrahedral and the trigonal carbons, and about the bond between the tetrahedral carbon and the trigonal nitrogen of the double bonds, of simple, non-conjugated aldimines. RESULTS 1. Chemical Shifts and Configurations of Ketimines Table 1 summarizes the chemical shifts of N-methyl ketimines; numbering corresponds to 16. The chemical shifts H ‘3'“? HB Ha H H (t_ra_p_§> (c_i§_) 16 are accurate to.i 0.05 p.p.m. for methyl protons; they are less accurate for methylene and methine protons. The acetone and 5-pentanone methylimines provide clear evidence that n.m.r. differentiates between the dsmethylene, or and 8—methyl protons gig and trans to the N-methyl group. While gis— and trans-oemethyl protons of N—methyl dimethyl ketimine are evident in Spectra taken of the neat liquid, in carbon tetra- chloride or in benzene solution, only in benzene solution are the_gi§- and trans-oemethylene and B-methyl resonances of N—methyl diethyl ketimine well enough distinguishable to elicit the separate chemical shifts. The cis-trans assignments are illustrated by considering N—methyl ethyl methyl ketimine, whose spectrum is shown in 10 11 .@fl ou monommmnnoo mcflumnfidc “0 0mm pm cmMMp mmSHm> .ponHpHSE onmEoo E .mmHHm>o mcououmlmcmup pom ImHU .mcououmlmcmnu Eonm mocmummnoucH em.m om.m em.m mm.R Ha.m ammo 2H Rm mmmo mmmo em.m ooo.m uoo.m om>.> omR.R wfioo ca Rm mmmo mmmo «m.m 0mm.m 0mm.m omR.R omR.R ummz mmmo mmmo 00.5 om.m mm.m ammo an Rm mm¢oamn mmo oo.> mm.m mm.m «moo 2H Rm mmaouw. mmo mm.m mm.m Rm.m pmmz mm¢ouu mmo Ro.R Rm.m Rfi.m 50R.R me.m «m.m mmmo an Rm mmmoumn mmo mo.» fio.m n smm.R ma.m mm.m «moo :H Rm N.mmoum. mmo 00.5 fio.m Q Emm.> mfi.m Rm.m ummz Fmucus... mmo fio.R em.m em.m am.> mo.m «H.m mm.m mmmo 2H Rm mmmo mmo mo.R oo.m ooo.m mm.R b ma.m Rm.m «moo as Rm mmmo mmo ao.R do.m oao.m am.> n efi.m Rm.m ummz mmmo mmo mo.R Ro.m «m.m mmoo :H Rm mmo mmo «0.5 oeem mm.m waoo ca Rm mmo mmo mo.R oa.m, mm.m pmmz mmo mmo mcmuu mac mcmuu momma mHo mummy mHo ucm>aom .Nm Hm mmouz amonm \mmoLa mmoLa , mmozuommam .E.m.m as mmcHEflumm H>£um2rz mo AmQSHm>IPV muMHnm HMUHEmSU .H magma .m 12 Figure 1, and N-methyl isopropyl methyl ketimine. Their spectra exhibit two sets of or and B-methyl proton resqe nances; the sets of ormethyl proton resonances are present in ratios of 6:1 for N-methyl ethyl methyl ketimine and 25:1 for N-methyl isopropyl methyl ketimine. The configurational assignments are based on the reasonable assumption that the predominant resonances arise from the syn-isomer, which is defined as that isomer having the N-methyl and oemethyl groups gig to each other. Table II summarizes the chemical shift differences, A6, between the gis- and trans-protons of the ketimines; these values are accurate to better than .i0.01 p.p.m. The gynyagti ratios, which are accurate to.iS%, were determined by integrating the two types of owmethyl protons. Assuming that these ratios reflect the thermodynamic equi- librium illustrated in Chart 1, the free energy differences CH CH / 3 3\ N K N ll 1 eqr 1% H c «v c R’/ \‘CHg R// \\CH3 Chart 1 between the isomers were calculated by the usual relationship, given in equation 1. Table III summarizes these results. AGO = —RT in K 1 13 .UHDUHH ummc map mm cmxmu mGHEHumx stume Hmnum Hmnumfilz mo Esuuommm .H.E.z o .85 .m.2.B ,rrlmmOIQII\ >N.® dd :1: _ mmULC mHU \ / 03 .m a®.> Flllllwmoiolllk .mmoio Imcmnu 60.5 mmUlZ .H musmflm 14 umnu mammE moam>_m>fluflmom m .mmaum>o Maucmummmm mcououmlmamuu paw ImHU Q .Uamflm UHuocmmE Hmsmfln m um mummmmm cououmlmflo may “.E.m.m CH ompuommu mum mmzam> one .oom um cmxmu mmDHm>m em.o mH.o mmoo ca Rm mmmo mmmo o n «moo 2H Rm mmmo mmmo o Q ummz mmmu mmmo n ON .0 me .o ammo 5” Rm humouw. £6 a n aa.o «Hoo ca Rm NAmmonia... mmo Q n mo.o ummz sumoufl mmo n om.o ma.o mm.o ammo :H Rm mmwo mmo n n n mfi.o «Hoo cu Rm mmmo mac n A n me.o pmmz mmmo mmo Rm.o omoo as Rm mmo mmo ma.o waoo :H Rm mmo mmo ma.o ummz mmo mmo 38.5 2 Ammoum c 2 Ammonia Z4 $5.3 34 £838 mm Hm mmozuommam mHU mmcflaflumz Hsrumzlz “om A . s I ©c©< .HH magma m 15 oa Table III. Isomer Distribution, Ke a! and AG for N-Methyl Ketimines q R CH3 CtzNCHs syn/antib Ke AGO in kcal./mole ratio q C2H5 86/14 0.164 1.51 .i-C3H7 97/5 0.059 2.69 E-C4H9 100/0 < 10-2 > 2.7 gFor equilibrium described in Chart 1 at approximately 250C. bSyn-isomer defined as that in which the ormethyl and N-methyl groups are cis. 16 2. Effect of Solvent on the Chemical Shifts of N-Methyl Ketimines Table IV compares the chemical shifts of N-methyl ketimines in benzene and in carbon tetrachloride; a positive Av value signifies that the chemical shift appeared at a higher magnetic field in benzene than in carbon tetrachloride. Though Av values for methyl protons are accurate to ifiJS c.p.s., they are less accurate for methylene and methine pro— tons. While gig—protons exhibit positive Av values, trans protons exhibit either comparatively smaller positive values or small negative values. In the series of dbmethyl ketimines, Av values for gigfohmethyl protons decrease markedly as the size of the other alkyl group increases. Similar but smaller trends occur in the Av values for trans-db,_gi§-B, trans-B- methyl protons. Figure 2 shows the effect of benzene dilution on chemical shifts of the various protons of N-methyl ethyl methyl ketimine. A positive A6 value means a higher magnetic field proton resonance in benzene than neat. 5. Chemical Shifts and Configurations of Aldimines Table V summarizes the chemical shifts of N—methyl aldimines in various solvents. Table VI compares the chemical shifts and vicinal Spin-Spin coupling constants of some th- octyl aldimines with those of the corresponding N-methyl aldimines. The chemical shifts are accurate to.i0.05 p.p.m., except those for the ormethine protons which are reported as 17 mum GOHHDHOm mofluoasomuumu conumo CH msououmlmsmuu cam ImHU mnu mo muMHnm HMUHEmSU .A.>\.>v mGOHuSHom Rm Mom .m.m.0 GH Umuuommu “A > I >v u >< .Hmoflpcmofl Umumoflmcoo .UHmHm Uflpmcmma Hmnmfln m um mummmmm mcmncmn SH UMHQm Hmoaamnu map momma osam> m>HuHmom ¢ ¢Hoo. ammo . . I . . . m m m N a 0+ am e OHm ma+ OHo ma+ Qm mfi+ m o m o m.o+ m.mu N.Rfi+ mmsoum. mmo m.m+ o.m- O$042+ m.e+ m.fi- m.om+ Nmacaw! mmo o.a+ m.mu Qméa+ O1.m+ OHm.mfi+ R.o+ ¢.mm+ mmmo mmo R.on ¢.e+ m.mm+ mmo mmo mcmnu mHU mcmnv mommy mHo msmnp mHU mm Hm Ammonzv>< Ammoamv>< Amoicv>< Ammoiov>< Ammoicv>< mmozuommdm mooHHoHsomume GOQHMU paw mcmNsmm GA mmcHEHumm ahzuGZIZ mo mumaflm HMUHEmSU mo somHHmmEoo .>H mHQMB A6 in p.p.m. A6 in p.p.m. Figure 2. 18 N 0.5r— . C CH . CHB/ \CHZCHg 3 . O. 2 F: N/ o p || ' /c\ O O' 1 — £113 CH2CH3 ‘ //933 N g 0'1 ‘ CH3CH2 \CH3 : :V4TI : 5, °'\ 000— Q m ' o (M— ___€Hglg v C>C> ® “-001 "" l l I 1 l I l J J 10 50 50 70 90 -- Weight percent of N-Methyl Ethyl-—> Methyl Effect of benzene of N-methyl ethyl Ketimine dilution on the chemical shift methyl ketimine. 19 omscflucoo mm.m mm.m Ewm.m mm.m «Hoo Rm mmmo mmo om.m m ssm.s om.m mcoz mmmo mmo mm.m mo.m som.s m mmmo Rm mmo mmo «m.m Rm.m smm.R mm.m «moo Rm mmo mmo mm.m mm.m asm.s mm.m mcoz mmo mmo Rm.m mm.R mm.m memo Rm mmvoum. m mm.m «m.R we.m ¢Hoo Rm mm¢oum. m Rm.m mo.m m mmmo Rm N.mmo....m. m «m.m mm.» om.m waoo Rm bmmoum. m mm.m mm.> we.m mcoz hmmonm. m mm.m mm.> mm.m memo Rm mmmo m mm.m em.» me.m iJoe Rm mmmo m mm.m mR.R mm.m mcoz mmmo m mm.m wo.m ERm.R m mmmo Rm mmo m mm.m mm.m sow.» mm.m «H00 Rm mmo m om.m Rm.m Emm.R mm.m mcoz mmo m om.m em.m NR.N momo Rm m m mm.m ma.m «¢.m waoo Rm m m mmouz mmoum mold £06 £05 E usmfiom mm Hm Imsmuu Imcmnu Imamuu Imcmuu mHU mmozumomommdm mmafleflwae HmaumSIZ mo Ammszm> I so mumflgm Hammsmro .> magma 20 . mUflmhmemUCH UC®>H 0mm .umHmHuHsE memEOUE .Mfl.ou monommmnuoo mcflumnasc “0mm um cmxmu mmsHm>d Rm.m m m memo Rm AHIV mm.m m Rm.m wfioo Roe A V mm.m m mm.m maoz AHHWV mm.m amm.R ms.m memo Rm mmwoum. mmmo om.m Esm.s om.m saoo Rm mm¢oum. mmmo ms.m sem.s mm.m maoz mmaoum. mmmo mR.m amo.m Re.m «moo Rm mmmo mmmo RR.m soo.m me.m mcoz mmmo mmmo mm.m oo.m smm.R Hm.m «Hoo Rm mm.m oo.m Ems.» mm.m ummz bmmoum. mmo mm.m mo.m smm.R m~.m memo Rm mmmo mmo mmoIz amoum more mmoIc mmoio Hm ucm>aom mm Hm Imcmuu Imcmnp Imamuu Imcmuu mHU mmozumumummam oGUCHusou I > magma 21 Table VI. Comparison of the Chemical Shifts (T-Values) and Spin— spin Coupling Constants (JH H ) in c.p.s. for N-Methyl and N-thctyl Aldimines l a RlRZCiI-CI: : NR3 HcfilRa r—c(CH3)2CH2C(CH3)3——\ ,7 CH3 9, R1 R2 1H1 THOI JH1H0I THI THO, JHlHOL H H 2.42 8.12 4.68 2.58b 8.09b 4.79b 02H5 H 2.45 7.90 4.04 2.56 7.80 4.07 .n-C4H9 C2H5 2.57 7.95 5.57 2.59 7.94 5.54 aValues taken at 560 for neat liquids except where otherwise indicated. b5% solution in carbon tetrachloride (v./v.). 22 centers of multiplets. Figure 5 demonstrates the nature and assignment using N-methyl and Nag-octyl orethylhexylaldimine as examples. The designation of protons correSponds t0.ll for N-methyl aldimines and to 4Q for Nit-octyl aldimines. I I CITE-7‘1““? WENT??? H6 H8 H1 HN HE3 Ha H1 (I: H2 C H3 H4 17 18 Chemical shift data for various alkylamine derivatives of acetaldehyde appear in Table VII; 11 depicts the numbering of the protons. The spectrum of N-isopropyl acetaldimine in Figure 4 illustrates this class of aldimines. Since n.m.r. distinguishes between gig- and trans—0+ methyl protons of N-methyl ketimines, and on the reasonable assumption that the n.m.r. of Schiff bases follows trends similar to those observed in analogous systems (42,45), the presence of only a single H1 resonance implies that N-methyl aldimines exist in one configuration only. Though special care was extended to the study of N-methyl acetaldimine, in neither the H1 nor the ormethyl region could evidence of a second configuration be detected. The similarity in chemical shifts and vicinal spin-spin coupling constants of the Nfit-octyl and the N-methyl aldimines leads to the conclusion that all aldimines exist exclusively in the same configuration; 25 N-CH3 (a) T.M.S H1 (Ti-CH r T = 2.57 6.77 8.00 0 Ho 9 (b) T.M.S H1 OI-CH r} b M // L W I F l T = 2.59 7.94 0 HQ > Figure 5. Spectra of N-methyl osethylhexylaldimine (a) and Nit-octyl onethylhexylaldimine (b) taken as the neat liquids. 24 Table VII. Chemical Shifts (T - Values) for N—Alkyl Acetaldimines in p.p.m.a CH3CH=NCHR 1R2 R1 R2 H1 N-CHs N-CH2 N—CH (l-CH3 H H 2.58b 8.81b 8.09b H CH3 2.55 6.78 8.18 H Achs 2.57 6.75 8.15 H .n-03H7 2.45 8.80 8.17 H n-C5H9 2.45 8.75 8.17 H C6H5 2.59 5.85 8.26‘ H CSHS 2.50b 5.55b 8.21b H .i-C3H7 2.42 8.87 8.14 CH3 CH3 2.55 8.78 8.19 ch5 chs 2.45 7.41 8.15 aValues taken at approximately 400 as neat liquids except where otherwise indicated; numbering of protons correSponds to 11, b5% solution in carbon tetrachloride (v./v.). 25 .UHSvHH umm: mnu mm smMMu msHEHUHmuoom ammonm0mHIz mo Eduuommm .H.E.z .8 musmflm O mfi.m IIt; .m.z.H nmolo omfimmov A Al om m>.© mm.m H P ( EUIZ II\ (II Hm IIK 26 on steric considerations they are assigned the configuration in which the N-alkyl group and H1 are gig. This configur- ation will be referred to as syn, To exclude the possibility that the presence of one isomer resulted from the combination of kinetically controlled formation (1,45) of only the gygyisomer and a low rate of configurational isomerization (11), an attempt was made to isomerize N—methyl acetaldimine (Chart 2). The method, which CH3 CH3 CH3 // fiI/ Be N G blI/ ‘———— ll <——> BH /c /c CH3/ \ H CH2/ \H CH2/ \H 9 CH 3\ CH3\ CH3\ 8 N BH N N H ’—-— H 4——> ' c 8= 0 /c CH3/ \H B 8 CH2/ \H 0312/ \H Chart 2 consisted of adding an excess of the Schiff base to dimsyl sodium (5:1 mole/mole) in dimethyl sulfoxide (DMSO), failed to provide a suitable pathway to the antifconfiguration. Within 50 seconds of adding the aldimine to the dimsyl sodium in DMSO, a white, crystalline solid began to precipitate. The n.m.r. spectrum of an immediately removed sample of the DMSO solution exhibited resonances of the syn-isomer and none indicative of the agEi-isomer. All the resonances of the syn— isomer disappeared within ten minutes. 27 The repulsion energy between H1 and H5 in the anti- configuration of N-methyl acetaldimine (19, X=N) was calcu— lated to see if it would account for the differences in free energy and enthalpy between the syn: and anEi-configurations. Also, the repulsion energy between H1 and H6 for cis-butene—2 /\ X4 He c3 Hl ./ \82/ 1§_ (19, X=CH) was calculated for comparison with the experi— mental values of 0.7 and 1.0 kcal./mole for the free energy and enthalpy differences between gig- and Eransrbutene-Z (46). It was assumed that H1 and H5 are within 150 of coplanarity and that the bond parameters of N—methyl acetaldimine are similar to those of N-methyl formaldimine (47) and propene (50). Table VIII lists the bond parameters from which the values of r the distance between protons H1 and H5, HlHe' were determined. The gisfbutene—Z parameters which were determined eXperimentally (48) agree well with the listed values, which consider that butene-2 consists of two propenes. Table IX summarizes the repulsion energies calculated by the equations of Bartell (49), Hendrickson (50), and Scott and Scheraga (51). 28 Table VIII. Models for Calculating 1f6-Proton, Repulsions in cis-Butene-2 and anti-N-Methyl Pro ton Acetaldimine Model Bond Lengths Bond Angles cis-Butene-2 '7‘" (X=CH) a . . 1.0852 a ab . . . 111.20 a b . . 1.501 a . bc . . . 124.5 a c . . 1.556 a cd . . 124.5 a d . . 1.501 a de . . 111.2 a e . . 1.085 a anti-N-Methyl Acetaldimine b o b (x=N) a . . . 1.0892 b ab . . 109.5 b b . . 1.44 b bc . . 116.9' a' c . . . 1.50 a cd . . 124.3 a d . . 1.501 de . 111.2 e . . 1. 085 a X/ \Hl 41X BOA/(:17- )H H d\c5/eH65 /T180/:O,0’ aFor propene, reference 50. b For N-methyl formaldimine, reference 47. QHOE\.HMUM CH m .N CH H 88\m.m0u 180m.wucmxm 80H x HH.0 u m Hm moCmnmmmmo 0HOE\.Hmox CH m .N CH H 88\N.00I 1000.0Ivmxm 00H x 00.H u m cm mUCmHmmme mHsomHoE\mH0 CH > ..EU CH H 88\88I0H x NH.mI AmuoH x mwm.0\navmxm 8HI0H x 0m.0 u > m0 moCmummmmm 29 woo ©.O m.fi 00m.fi mH O.fi m.O M.N Nmm.fi OH 0.0 0.H m.m m00.H m m.H , H.H m.m 00H.H 0 mumcmusmImHu ©.# m.w mob: @mm.fi ma 0-0 0.0 .m;0H m00.H 0H 0.0 m.m 0.mH mm0.H m . mCHEHUHmumum mHos\.Hmox 0.0 mHoe\.Hmox 0.0 mHoH\.Hmox 0.0H mmo0.H O0 HanumsuzIHuam U mmmumCOm Q ComeHHUCmm m HHmuHmm mmdmu mumupmnsm mmuow COHmHCmmm mmHmHmCm COHmHCmmm UQUCOQICOZ UQHMHCUHMU .NH ®HQMB 50 4. Effect of Solvent on the Chemical _Shifts of Aldimines fTable‘X summarizes the effect of benzene on the chemical shifts of the protons of N-methyl aldimines; a positive Av value signifies a higher field absorption in benzene than in carbon tetrachloride. The trends are similar to those of the ketimines, for gisle protons exhibit larger positive Av values than the remaining trans-protons. In contrast to:the negative Av values of the trans—B-methyl protons of ketimines, those of the corresponding protons of aldimines are positive. Figure 5 shows the effect of benzene dilution on the chemical shifts of Nit-octyl acetaldimine. Again, a positive A0 means a higher field absorption in benzene than in the neat liquid. It is noteworthy that the various methyl pro- tons of the t-octyl group appear at lower fields in benzene than in the neat liquid. The differences in the chemical shifts of N-benzyl acetaldimine in the neat liquid and in carbon tetrachloride solution are summarized in Table VII. In the neat liquid H1 and osprotons appear at higher fields by 17.5 c.p.s. and 4.5 c.p.s., respectively. 5. Vincinal Spin-spin Coupling Constants of Aldimines: Conformations Along the Bond Joining Tetrahedral Carbon to Trigonal Carbon Table XI summarizes the vicinal Spin-spin coupling con- stants between H1 and osprotons of N—methyl aldimines. 51 .moCmummumHCH qu>Homm .mplmCmNCmn CH Q .UHmHm 0Hu0CmmE HmanC m um mummmmm 0C0NCmQ CH HMHCm Hwoaamso mmmo mCmmfi mCHm> 0>HuHmom 4 .A. >\. >v mCOHuCHom Rm How .m. m. 0 CH Umuuommn “A HUO> U>vn >48 0 .m+ m .0- 00 .0+ mmmo 0000.0. m .m+ m .0+ 90 0+ mmmo mmmo R .m+ 0 .m+ 0.0+ m 006 006 m .m+ m .0I 00 .0+ m 0m+oum R .H+ 0 .H+ m m nmnouw m .H+ u0.0+ Cm .m+ C mmmo m.N+ 0.m+ m.OH+ m m mmo m.m+ H.HH+ 0Ho.mH+ m m AmmoIzv >< AmmoIm 05 A Colo :4 Ammoio 0>< Ammoio :4 QB >4 mm Hm mmoznmomommHm 0UHHOHCUMH009 Conumo UCM mCmNCmm CH mmCHEHpHd Hmspmzlz mo muwHCm HMUHEmguwmo ComHHmmEoo .N mHnme 52 .mCHEHUH8umom HmuUOIMVZ Ho mumHCm HMUHE0C0 0Cu Co COHuCHHo mCmNCmn mo uommmm .m musmHm ATII.0CHEH©Hmumo< kuoolmrz mo pCmonm HCmH03.III 00 OR , OH _ _ H _ _ _ m. : H.0I . I - .0 mm WIT? mm a u u H E I m0.0.. - w. H nu 3 Q @ MW I. Q Q 3 o 8 8 8 I 8.8 _u .l mo.o+ .0. ® Au n .I. l . n.“ m I .w O+ . H HA 4‘ .04 8 II I.- 8818880 a 1888+ :86: o 0 85:8 B .... ® .. l m.0+ Hm® 35 .mUHuoanomupmu coflnmo CH A.>\.>V R89 .Umuwoflwafl mmHBHmnuo mumSB ammoxm mUHSvHH #00: How cmep mmsfim>m 88.8 88.8 88.8 88.8 AHHVV 80.8 88.8 88.8 88.8 08.8 08.8 8880 8880Lm 88.8 00.8 08.8 88.8 8880 mmmo 88.8 88.8 88.8 88.8 00.8 880 8880Lm 88.8 88.8 88.8 88.8 88.8 880 8880 80.8 08.8 88.8 8mo 880 OH88.8 088.8 OH88.8 88.8 88.8 m 8880LM 88.8 88.8 88.8 88.8 88.8 m 8880L8 88.8 88.8 88.8 88.8 m HammoLm 88.8 88.8 88.8 08.8 88.8 m 8880 80.8 80.8 80.8 88.8 80.8 m 880 988.8 88.8 88.8 88.8 m 8 000+ 008+ 008+ 088+ 088+ 00 088: 008: mm Hm .m.m.u £8,0m8m6 118 mEOZWWhWMmmHm m mmCHEHUH< Hmnumzlz mo muqmumcoo mcflamcoo aflmmlcflmm Hmsflofl> .HN GHQMB 54 Table XII lists the values of the four-bond coupling con— stants, between the H1 and the N-methyl protons, and the five-bond coupling constants, between the N-methyl and the osprotons. These values are averages from several measure— ments taken from the spectra of the H1 and the N-methyl pro- tons and are precise to.i0.04 c.p.s. Figure 6 shows the H1 and the N-methyl proton regions of the n.m.r. Spectrum of N-methyl orethylhexylaldimine. Most osmonosubstituted aldimines exhibit vicinal coupling constants which decrease with increasing temperature. Notable exceptions are N-methyl propionaldimine, whose vicinal coupling constant increases and the butyraldehyde, hexylaldehyde, and tfbutylacetaldehyde methylimines, whose vicinal coupling con- stants are temperature independent. Vicinal coupling constants of a,ardisubstituted aldimines decrease with increasing temperature, except that of N-methyl cyclohexanecarboxaldimine, which is temperature independent. While the four-bond coupling constants are independent of temperature and of size and number of 0%substituents, the five-bond coupling constants exhibit a relation to these parameters inverse to that of the vicinal coupling constants; that is, as the vicinal coupling constants increase, the five-bond coupling constants decrease. Table XIII summarizes the effect of solvent polarity on the long-range and vicinal spin—Spin coupling constants of several N-methyl aldimines. The values were taken in 5-10% (v./v.) solutions of the aldimines. 55 .A.>\.>v 088808£08Humu .Umu0088c8 mm8BHm£uo $8053 unmoxm 885088 ummc msu How cmxmu mm58m>m conumo £8 889 O 88.8 88.8 88.8 8m.8 88.8 88.8 08.8 08.8 88.8 88.8 88.8 88.0 88.0 08.0 N8.0 8mmo mm8ULm 08.8 08.8 88.8 88.8 88.8 88.0 88.0 88.0 88.0 88.0 mmmu mmmo 88.8 88.8 08.8 88.8 80.8 80.8 88.0 88.0 mmo 8mmokm 08.8 88.8 88.8 08.8 88.8 88.8 No.8 80.8 80.8 88.0 030 8mm0 08.8 88.8 88.8 08.8 8N.8 8N.8 8N.8 8N.8 mmo mmu . . . . . . . . m 8‘ ll. QN8 8 88 8 988 8 £80 8 QN0 8 £80 8 80 8 Qmm 0 m m U.W 88.8 88.8 88.8 88.8 88.8 88.8. 88.8 8N.8 88.8 m 8m00|8 88.8 88.8 88.8 88.8 88.8 88.8 8N.8 8N.8 8N.8 88.8 m 8mmo 08.8 08.8 08.8 88.8 m 830 908.8 988.8 m m 008 008 088 o0 008: 008 008 088 o0 008: N a .m.m.0 c8 .m.m.o :8 m m z” o 2% ”0% (Ilmmoumflwmommflm no.8. 8. IL r mmonznmoommflm .808 8 ..|Iu|\ 80:888884 8mnumzlz mo musmumsoo mc88msoo a8mmlc8mm mmcmulmsoq .HHN @8989 .m 56 0:“ mm smxmu 0:8888888mx03883pmlo 88£meIz mo Esuuommm \ / om f E {Illmmouzlk .885088 ummc .H.E.c 8M8unmm .8 musm8m 57 .A.>\.>V 808:8 mum 8:088:808 Q .m.m.o Q8 8:8 .0 088 um mHm mm58m> 88¢m O 80.8 80.8 88.8 88.8 88.8 88.8 88.8 88.0 88.8 88.8 88.0 88.8 8880 8880Lm 88.8 08.0 08.8 08.8 08.0 88.8 8880 8880 80.8 88.0 88.8 88.8 80.8 88.8 8880 880 88.8 80.8 08.8 88.8 88.0 08.8 m 8880LM 88.8 88.8 88.8 80.8 88.8 08.8 m 8880 88.8 88.8 08.8 88.8 88.8 08.8 m 8 Z a z z a 0 8 Z z a 8 88 8088 m 88 8 88 8888 p 8 88 mm Hm rIIIIIII 8 888888808808 .«x ,(IIIIII n mcmxmnoao8o «8 mmozumomommam 8 888858888 Hmnumzuz 80 mpcmumcoo mc88msoo c8mmlc8mm mmcmulmcoq 8am 88C8UH> no pcw>8om mo pommmm .HHHx 08388 58 The stereochemistry about the bond joining the spa and Sp3 carbons is best described by g9 and g; for armonosubsti- tuted aldimines and gg and gg for a,d%disubstituted aldimines. H N”CH3 H N”CH3 R N”CH3 ‘ H J\H H H/ R/ H/ R H H a b E _2_1 H N”CH3 Rl N”CH3 R2 N/CH3 / H é/‘LH H R1 R2/ Ii/ R2 H R1 a b 22 23 The trends in vicinal spin-Spin coupling constants with changes in the size of dksubstituents and solvent polarity support this assignment. For example, changes to larger alkyl groups or more polar solvents are expected to increase the population of g9 and g; at the expense of g; and gg, respectively. With the logical assumption that J (vicinal coupling constant of t 2) is greater than Jg (vicinal coupling constant of gg), such _ changes will be accompanied by increases in the vicinal coupling Constants, as is the case. H N//CH3 R ,/"CH3 If staggered conformations gg and gg described the 59 conformations of aldimines, increase of solvent polarity would cause an increase in the population of rotamer gg. From where J . c 15 is the vicinal coupling constant in Jcis > J1200’ g_ and J12OO that in 2g, such a change would be accompanied by a decrease in the vicinal coupling constant. Table XIV summarizes the rotamer distributions about the carbon-carbon bond of the N-methyl aldimines; Table XV shows the effect of solvent on this distribution. Equation 2 was used to calculate the p0pulations of the proton eclipsed rotamers of the Okmonosubstituted aldimines, 29. In this J = J+J 2+ 1- J-J 2 y(t g)/ ( y)g obs cor equation, y is the fractional population of 29 and (l - y) that of 2;; J is the trans-vicinal coupling constant (for t 22); J9 is the gauche—vicinal coupling constant (for 2;); and Jcor is the effect on coupling when an Okproton is replaced by an alkyl group. The relative rotamer distributions for a,a+disubstituted aldimines were calculated from equation 3, J = th + (1 - y)J — 2J obs g cor 5 where y is the fractional population of 22 and (l - y) that of 2§, Jcor was evaluated from systems in which the various rotamers were present in equal populations; equation 4 ex- presses the vicinal coupling constant for this state, where n 1 =._ + _ 4 J 5 (Jt 2J ) n J obs cor .A.>\.>V 088808308880u conumo C8 :o8u58om 808 Homo . m/xo mwvm 880128 //m 88 ucmmmum 88 02888888 mc8c8mamu 088 Q .8088088c8 088380£uo 080:3 pmmoxm 8885088 880s 80mm 40 88.0 88.0 08.0 88.0 88.0 08.0 88.0 88.0 88.0 88.0 8880 8880Lm 88.0 88.0 08.0 88.0 8880 8880 88.0 88.0 88.0 88.0 88.0 880 8880Lm 88.0 88.0 88.0 88.0 88.0 880 8880 88.0 88.0 88.0 880 880 088.0 088.0 088.0 088.0 088.0 m 8880LM 88.0 88.0 08.0 88.0 88.0 m 8880L8 88.0 88.0 88.0 88.0 m 88880:m. 88.0 88.0 88.0 88.0 88.0 m 8880 88.0 88.0 88.0 88.0 88.0 m 880 0000+ 0008+ 0008+ 0088+ 0088+ 000 0088: 0008: mm Hm 8000880 . m/vlllokvm 880zum0mommHm 8 880:2\ xxm M mumfimuom ma8fi888¢.8%£u®2Iz mo mGO8uM8smom 0>8u880m .>HN 0.8.3.88 41 Table XV. Solvent Effect on the Relative Populations of N-Methyl Aldimines a H\ /N—CH3 b R1R2CHCH=NCH3 / ,c —— c / , percent / \ R1 R1 R H Cyclohexane Acetonitrile C2H5 H 0.65 0.72 “3-C4H9 H 0.96 1.00 CH3 C2H5 0.41 0.48 C2H5 C2H5 0.49 0.55 fl-C4H9 C2H5 O. 51 O. 58 <:::> 0.29 0.34 aAll values are taken at 560. bThe remaining aldimine is present as i7 \\}i 42 is the number of arprotons replaced by alkyl groups. The vicinal coupling constant of N-methyl acetaldimine, 4.76 c.p.s., provides the value for n = O. The value of 4.50 c.p.s. for Okmonosubstituted aldimines, where n = i, was de- termined by two methods. Since the coupling constants of N-methyl butyraldimine and N-methyl hexylaldimine are inde- pendent of temperature, the three rotamers must be present in approximately equivalent populations. Their coupling constants agree well with the intersection of the vicinal coupling con- stant Xfi- temperature plots for N-methyl propionaldimine and N-methyl isoamylaldimine depicted in Figure 7. This inter- action is taken as the "free rotation state," that state in which all rotamers will be equally populated because of fast rotation about the carbon-carbon bond. Though the actual curves are expected to assymptotically approach this value as a limit, the use of this intercept provides a fairly accurate method of estimating it. Since the coupling constant of N-methyl cyclohexane— carboxaldimine displays temperature independence, its rotamers must occur in equal populations. So, its vicinal coupling constant, 5.86 c.p.s., supplies the n = 2 case. From these values, the effect is found to be approximately 0.45 c.p.s., which agrees well with the value of 0.40 c.p.s. for the effect of an osalkyl substituent on the correSponding vicinal coupling constants of aldehydes. The value of 0.40 c.p.s. was used in these calculations. 45 0000008500 .0> mmozumommommo E “mm0onmmoaammonm A80 I. 0 .8 kmmoZumOmmommmo Amy “mmvzumUNmormmUI8 A80 808 . m Eb .0C88Q500 8mc808> .8 wnsm8m Alloofiall 008 008 068 0m8 0N8 088 008 00 00 08 00 on 08. 0m 0m 08 AV 08I ONI 0m! H 0 _ _ 8 A.-- 8 _ 8 — 8 _ _ _ _ _ _ 8 _ . - 8.8 B 0.8 a a m 0 a] _ 1 N.¢ .m.m.0 “lull! “I, m w fl m ml CH. 0 N I 0.0 m 80 a . . .8 .. e 8 - 0 I. mtnv 44 The vicinal coupling constant of N—methylfiE-butyl- acetaldimine supplies the necessary information to calculate Jg and Jt. This aldimine is assumed to exist in the proton eclipsed rotamer only, g9; so, equation 5 expresses its ob— served coupling constant. Using its coupling constant in = 4 — Jobs 2 (Jg + Jt) Jcor 5 acetonitrile, 5.57 c.p.s., and the 4.50 c.p.s. value for the Okmonosubstituted aldimines described by equation 4, n = 1, the values Jg = 2.55 c.p.s. and Jt = 9.65 c.p.s. are derived. Table XVI summarizes the free energy differences between individual rotamers; Table XVII shows the effect of solvent polarity on these differences. The values were calculated by the usual relationship, equation 1. Table XVIII summarizes the enthalpy differences between the rotamers which are calcu— lated from equation 6 by plotting log K gs. 1/T7 0 AH = —2.505 R A logKeq A 1/T Figure 8 provides an example of this method. Using JC values of 0.5 and 0.5 c.p.s. affected AH0 and or AGO by approximately 5%. With the values Jt = 9.2 c.p.s. and J9 = 2.5 c.p.s., the AH0 values also differed by 5%. 45 8008mmsm 805000 05 0>0£ 80580> 0:0..0500 0Q 00: 8883 8830 00580 00008800 0m 000 0080000 00808800 8m 80 80080085000 0030 085080 .0080050080 0000888008 00 w800 0005 080 0:0 000008885088 .A.>\.>v 0080083008000 009800 58 .80500 080 8080008 000800850800 0380 G08. 5 Om HO .0 8 808 80 .000008088 088300300 00033 um0ox0 8085088 0000 0080 00.. 00: 00... 08.. . 000+ 080+ 080+ 080+ 080+ 000+ 8800 0000Lm 088+ 088+ 080+ 088+ 8000 8000 088+ 088+ 008+ 088+ 088+ 0880 0800Lm 088+ 088+ 088+ 088+ 088+ 0800 8000 08+ 08+ 00+ 880 800 . . . . _ . m 0800LM 0088 8+ 0088 8+ 0088 8+ 0008 8+ 0088 8+ .: 08+ 088+ 008+ 008+ 088+ +080:0 08: 08: 08: 08: 8 H8880.0. 08: 08: 08: 08: 08: 8 m800 0mm: 080: 00m: 08m: 088: m 800 l I N _ .8. 0008+ 0008+ 0008+ 0088+ 0088+ 000 0088 0008 8 8 0 0 m 1 /U III UN\H.H lily /U U\\ HOW mvfl \ mmUZHmUmUNMHm m V / /H \\ / 0 80:2 8 800::2 0 mH080uom 0088808¢ 8%3002Iz 80 04 .H>N 0830B MO 46 Table XVII. Effect of Solvent on AGO of N-Methyl Aldimine; Rotamers H\\ éN-CHSAR\\ d¢N-CH3 AGO cal./mole for /C_C : /'C— \ R leCHCH=NCH3 / / \ H // H R H R1 ' R2 Cyclohexane Acetonitrile C2H5 H ‘70 +150 _t__-C4H9 H +1, 510 ‘>+2, 700 CH3 ch5 +220 +560 chs C2H5 +590 +550 .g-C4H9 chsa +440 +630 -120 +20 aThe calculations assume that the populations of R1 eclipsed rotamer and R2 eclipsed rotamer are equal. Since this will not be true, the values have no actual physical significance and are used only to facilitate discussion. 47 Table XVIII. AHO for Rotamers of N-Methyl Aldimines a H0 in cal./mole for R1R2CHCH=NCH3 H\C __ C//N-CH:3,__A R>C — CéN-CHS R1 R2 R<;7 \\H -‘—‘ IY/l/ \\H CH3 H -100 chs H 0/0 n-CsHll H “/0 i-C3H7 H +350 E‘C4H9 H > +1 , 000 CH3 CH3 +90 C2H5 CHsb +260 27C3H7 CHab +500 C2Hs C2H5 +440 BfC4H9 C2H5b +550 aValues for aldimines as neat liquids. bThe calculations assume that populations of R1 eclipsed rotamer and R2 eclipsed rotamer are equal. Since this will not be true, the values have no actual physical signifi- cance and are used only to facilitate discussion. 48 .088888ws008 00%500808w0588hn008lo 808 B\8 .0 IN / 8|.m00 08 008 x B\8 0.0 m.0 N.0 8.0 0.0 m.& m.m >.m ©.m m.m 0.m m.m N.m d.m Au.m m.m M OHmOQ .8 08sm8m 8 _ 8 8 _ _ 8 8 _ _ _ _ _ _ _ _ 80.8- n 00.0 I 80.8 I. 8 86 flu . T; l.— 9 00 = 0 m0 0 9 my 0808 .800 088+ u Au 008 8 [Mi 30.80880- u 8\8 0 . 000:0 8 m Ndofi m8. ki 80. mm. mm. mm. 08. 49 6. Long-range Spin-spin Coupling Constants of Aldimines: Conformations Along the Bond Joining Tetrahedral Carbon to Trigonal Nitrogen Table XIX and XX summarize the vicinal and long-range coupling constants, respectively, of N-alkyl acetaldimines. The values are averages of several measurements taken from the H1 and the 0+methyl proton regions; their probable error is.i0.04 c.p.s. Figure 9 depicts the partial n.m.r. spectrum of N-ethyl acetaldimine. Neither changing temperature nor replacing N-methyl pro- tons with alkyl groups affected the vicinal coupling constant, J . Though both the four-bond coupling constants, J H H HlHN' and the five-bond Coupling constants, decreased when JHgflN’ an N-methyl proton was replaced by an alkyl group, neither the size of the alkyl group nor temperature affected the coupling constant, except for N—cyclohexyl acetaldimine. This lone exception exhibited an increase of approximately 0.2 c.p.s. in the four—bond coupling constant in a 1000 temperature range. Though N-dialkylcarbinyl aldimines showed no clear five-bond couplings, their 0+methyl proton resonances were broad. Since five-bond coupling constants of the QFSubstituted N-methyl aldimines and the four-bond coupling constants of 3-substituted propenes reflect the distribution of "C-C" rotamers (28,29,56,37), they are expected to reflect ”C—N" rotamer distributions of the N-alkyl acetaldimines. Since all long-range coupling constants are independent of the size of 50 .000008008 008380000 08053 .0088080008000 008800 :8 A.>\.>v 8088 080080 0085088 0008 808 00x00 00580>0 O 88.0 88.0 08.0 88.0 88.0 88.0 08.0 8880 8880 88.0 080 080 88 .0 08. .0 8 0800.8. 88.0 88.0 88.0 08.0 08.0 m 0800 88.0 88.0 08.0 8 0800.8. 88.0 88.0 8 N800:8 88.0 8 8880 88.0 8 080 088.0 888.0 m m 00008+ 00088+ 0008+ 0008+ 0000+ 0008+ 08 88 r. .m.8.0 08 _0888 888880280080 0008888800008 8hxd¢lz 808 008000000 08888500 G8m0188mm 800808> .NHX 08808 M 51 .00800800 .8008 80 00083:88m0 u 030 .A.>\.>V 0088088008000 808800 :8 00805800 808 8 .000008008 008380000 08003 0m00X0 0085088 0000 808 00800 00580>0 088.0u03.m 88.0 88.0 88.0 08.0 88.0 AHHUV 088.0u03.m 08.0 88.0 8880 m8N0 U00.8u030 88.0 080 080 80.8 88.8 88.8 88.8 88.8 88.8 00.8 08.8 80.8 88.8 8 0800 88.8 88.8 88.8 00.8 8 8800L0 88.8 08.8 08.8 88.8 88.8 88.8 8 0800:8 08.8 88.8 80.8 88.8 8 F800:8. 08.8 88.8 8 8880 80.8 88.8 8 080 QN¢.fi - QO©.H m m 0008 0088 008 008 000 -008 0008 0088 008 008 000 008 N8 H8 rll 84 08.0.8.0 08 IL rlll 28 88 0.8.0 08 IIIIL N888 0:2 u 80:080 808 0 N8H8 0:2 n 0:080 808 0 0008880800008 8mx80 59 05.0 05.0 00.8 80.0 00 55.0 05.0 50.8 05.0 05 55.0 05.0 00.8 05.0 00 80.0 00.0 00.8 80.0 08 00.0 00¢0 08 00.0 00.0 00.8 80.0 0 00.8 05.0 08I 0 0 m 0 N 0 0 0 i000 0000 z I 0\00 A000 0 I 0\ 00 00 z 0\00 00 .0 00 \ I I I n . 000 /000 000\ /000 000\ /000 mmufl/luwmdu 0030000000 000 .0.m.0 08 00800000 0 00088800M 800002Iz 00 000000000 00800000 0800I0800 00000I00oq 000 00 00000000505 00 000000 .HHHNN 00008 .000 00 0080088 0000 000 00x00 00080>0 00.0 mm8UlM 00.0 08.0 00.0 0000.0 00.0 05.0 00.0 0000 00.8 05.0 00.8 000 H.H/ \ m l 0 0 000/2 u 0\ 0/ 000/0 I 0\00 000/0 I 0\00 000 £00 I /0\ I / 0 \ mmozuo A H.H\\ // m\\ // m 000 .0.m.0 08 00880500 000808000 000002Iz 000 000000000 00800000 0800I0800 00000I00oq .HHxx 00Q0B .m 60 these values are less accurate. Figure 11 depicts the Nemethyl and_gi§-0bmethyl proton regions of the N-methyl ethyl methyl ketimine spectrum. While the gig— and Egansfmethyl coupling constants are independent of the temperature and the size of the other 0+ alkyl group, the tgans-R coupling constants depend on the number of Ckprotons replaced by methyl groups. The Erggng coupling constants of both N-methyl ethyl methyl ketimine and isopropyl methyl ketimine are approximately 0.1 c.p.s. lower at 900 than at 00; this difference is within the expected experimental error. Table XXIV compares the five—bond coupling constants of N-methyl aldimines to the corresponding Erggng coupling con- stants of the ketimines. 8. Effect of Acid on the Nuclear Magnetic Resonance §pectra of Aldimines Table XXV compares the chemical shifts and vicinal Spin- Spin coupling constants of aldimines in acetonitrile before and after addition of perfluoroacetic acid. While for the unprotonated aldimines the chemical shifts are accurate to .i1.0 c.p.s. and the coupling constants to.i0.04 c.p.s., for the protonated aldimines the chemical shifts are accurate to .i2.0 c.p.s. and the coupling constants to.iO.1 c.p.s. The n.m.r. spectra of the protonated N—methyl aldimines displayed no long-range spin-spin coupling (Figure 12) and exhibited new peaks, which gradually increased in size at 61 .oflsvfla pmmc man no cmxmu mcflEHumx Hmnumfi Hmnbm ambumfilz mo Esuuommm .H.E.Q Hmflunmm \ /. om /rlllllmmoioumflo.llltll\ r, amouz .fifi musmflm 62 Table XXIV. Comparison of Long—range Spin-Spin Coupling Constants Between trans-0+ and N-Methyl Protons of Aldehyde and Ketone Methylimines FCHS a R1R2CH R3 Spin-spin Coupling Constant in c.p.s. R3 H CH3 R1 R2 H H 1-45 1.55 CH3 H 1.47 1.52 CH3 CH3 1.24 0.82 aValues taken for neat liquids at 560. .omoom Uflom OHumomouosamHHu mono a “maflubflCoumum CH A.>\.>v Romm .A.m.m.o 0.0 V mCmafimahbumEmnbmb mMB GHMCCMbm HMCHmuCHU .omumoHUCH mmHBHmzuo mumCB ammoxm .Umoom pflom UHumomouosawfluu mmouo meCBo .UmumoHoCH mmHBHmeo mHmCB ummoxm AmHoE\mHoEv Roanmn .Mfl.©Cm ww.ou mUCommmnuoo mCHHmQECZ .omm bm memu mGSHm>m 65 . . . . hawlllll mm mm» a mo new mms a me new m o u znmo mo ao.> m.mma m.am¢ m>.m m.mmfi m.me« mmoznmomomxmmmov mo.m m.mma m.mm¢ mo.m m.oma m.am¢ mmozumomOmmommmo mm.m N.mma m.mmw am.m m.amfi n.mma mmozumommommwoLM mm.¢ N.mma m.amw sm.¢ o.ama m.mm¢ mmozumommommao o a z a o a z a mmb one one mmh. was omo . . .m.©Hum.oHu®Um mHHHuHCoumom CH mCHEHoH< IOHOCHMHHH wwoom CuHB OHHHUHCoumom CH Q .m.Q.U CH mmeumCov UCHHQCOU CHQmICHQm UCm muMHnm HMUHEmCU mmcflsfloam mo manommm .m.z.z map so oflo< mo uummmm .>xx magma M 64 .UHom UHumomouosHmHHu mo mmoup mmubu mo COHunUm AQV Hmumm UCm Amv muommfl mHHuuHCObmum CH COHuCHOm A.E\.Ev &m mm mCHEHUHMHMuDQ thumfilz mo moCMCome Hm .NH mHDmHm A. om Am; 33 65 the expense of the aldimine peaks until the spectra of the aldimines eventually disappeared. Attempts to take the spectrum of the protonated N—methyl acetaldimine failed. While attempts to take the spectrum of the protonated Nip-octyl acetaldimine in 5% solutions were unsatisfactory, in a 20% solution a suitable, reproducible spectrum was obtained. The spectrum had to be taken quickly, since it disappeared within five to ten minutes after acid addition. Although the chemical shifts between protonated and un- protonated aldimines differ by values greater than the expected error, the differences are of random size and direction and never exceed 15 c.p.s. The vicinal Spin—Spin coupling con- stants tend to be higher for the protonated than the unpro- tonated aldimines. However, only for N-methyl dbmethyl— butyraldimine and d+ethylbutyraldimine are these differences greater than the expected error. DISCUSSION 1. Configurations The chemical shifts of N-methyl ketimines listed in Table I provide clear evidence that n.m.r. distinguishes between deethyl protons gig and trans to the N—methyl group. -Since methyl groups of olefins possess identical chemical shifts whether gi§_to another methyl group or to a proton (52), the separation of 0.1 p.p.m. between the gis— and trans—0+methyl protons in the Spectra of the ketimines taken as neat liquids or as solutions in carbon tetrachloride must arise from effects of the nitrogen nondbonded electron pair. Though the gig: and trans-ormethyl protons are distinguish— able, the methylene portion of the spectrum of N-methyl di- ethyl ketimine does not exhibit the doubling characteristic of gig: and trans-dkmethylene groups. Possibly, a separa- tion does exist, but is obliterated by the large amount of Spin-spin coupling. Similarly Staab, Vogtle, and Mannschreck (12) detected distinct gig— and trans-osmethyl groups for_§21, but observed only a single resonance for the okmethylene protons of §§b_when their spectra were taken in carbon tetra— chloride solution. 66 67 l ‘\ x—ez bII E (a) R = CH3 | c c (b) R = chs R/ \R R/ \R 52 The syn/anti ratios for N-methyl ketimines are commensur- ate with those of other nitrogen containing derivatives of ketones (42,45). For example, the syn/anti ratios for semi- carbazone and ring-substituted phenylhydrazone derivatives of butanone range from 90/100 to 80/20 in comparison to the N—methyl ethyl methyl ketimine syn/anti ratio of 86/14. However, whereas the syn/Egg; ratios of most derivatives of acetaldehyde range between 75/25 and 50/50, only the syn: isomer of any N-alkyl acetaldimine or any other N—alkyl aldimine is detectable. .This exclusion of the anti-configura- tions of N-alkyl aldimines could result from a free energy preference for the syn-configuration by at least 2.2 kcal./ mole, or it could be the result of kinetically controlled formation of only the syn-isomer if the barrier for inversion of the N-alkyl group were too high. The rate determining step in the formation of Schiff bases in an alkaline medium has been shown to be the base catalyzed dehydration of the intermediate amine alcohol, Chart 5 (55,54). 68 9 HO NH H R / , i // :> /H ,fiNfl—W—fi: % R 5;..SN=_—c<--R R/ QOH 9 HOW H /H R /H R\\ IW M ¥ R\\N:C‘*/‘BER N —,c r 0 C I Chart 5 Since the activation energy in a dehydration of this type reflects steric compression in the transition state (55), having the alkyl groups gi§_will cause a higher activation energy than having them trans. Thus, the gyneisomer would form faster than the anti. The literature does not provide any exact information for the rates of isomerization of these aldimines. However, Curtin's theories (11) regarding the iso- merization of Schiff bases suggest that these rates of isomeri~ zation will be of the same order as the rates for isomerization of ring-substituted acetophenone methylimines. If so, a first order rate constant between 10'4 and 10'6 sec.‘1 at 600 would be a reasonable estimate. A rate constant in this region would yield the equilibrium mixture under the conditions em- ployed. The repulsion energies listed in Table X support a large free energy difference between syn: and anti isomers of N-methyl acetaldimine. While repulsion energies for gi§~ butene-2 calculated by the equations of Hendrickson and 69 Scheraga compare favorably with the observed enthalpy dif- ference of 1.0 kcal./mole between gigf and trgggrbutene:2, the repulsion energies calculated for aptifN—methyl acetale dimine indicate a free—energy difference sufficiently higher than the 2.2 kcal./mole necessary to explain the exclusive presence of the syn-isomer in the equilibrium mixture. 2. Interaction with Benzene Since both aldimines and ketimines exhibit larger Av values for protons cis to the N-alkyl group than for protons trans to it, the Specific interaction with benzene depicted by 58 is suggested. This solvation interaction resembles N/CH3 N/z H H /c \ c R2 ‘ R2 R1 38 54 the proposed interaction between benzene and nitrosamines or oximes, §4_(44,45). Since the interactions for the nitro— samines and oximes result from an electronic repulsion between the oxygen electron pairs and the benzene Rifelectrons, a similar repulsion between the nitrogen electron pair and the benzene pi—electrons couldconceivably explain the inter- action postulated here for the Schiff bases. The decrease in the size of the Av values with increase in the size of the 0% or N-alkyl groups can be explained by 70 increased steric repulsion causing a lower association con- stant for the equilibrium described by Chart 4. R1R2CH=NCH3 + CsHe A R1R2CH=NCH3°C6H6 Chart 4 5. Conformations Only for N—methyl prOpionaldimine is the rotamer in which the alkyl group eclipses the imino nitrogen, 55, more stable than the rotamer in which the proton eclipses the nitrogen, .ég. While this aldimine exhibits a 100 cal./mole enthalpy CH3 CH3 / / N N / H / H R H 55 56 difference in favor of rotamer 55, for N—methyl butyraldimine, heptylaldimine, and cyclohexanecarboxaldimine this difference is about zero. For all other aldimines, rotamer 55 is favored. The enthalpy difference by which it is favored increases as the size of the 0Hsubstituent, R, is increased. The solvent dependence of the vicinal coupling constants of the N-methyl aldimines most likely reflects changes in rotamer distribution due to differences in the dipole moments of the individual rotamers; rotamer 51, in which the proton eclipses the imino nitrogen, has a larger dipole moment than .58, the rotamer in which the alkyl group eclipses the nitrogen. 71 In going from cyclohexane to the more polar solvent aceto- nitrile, the ratio 51/58 therefore increases. This increase results in an increase of the coupling constant. Part of the increase in the coupling constant, however, must be caused by another factor, as evidenced by the 2% increase in the vicinal coupling constant of N—methyl acetaldimine° To explain the existence of N-alkyl acetaldimines in conformation 58 only, free energy differences between 58 and 49_of 2.2 kcal./mole or greater are necessary. If the I II | H N R N 3/ 3/ R H 59 4O temperature dependence of the four-bond coupling constant of N—cyclohexyl acetaldimine reflects a change in the distribu— tions of rotamers 58 and_4g, not more than 15% of rotamer 49 in the mixture at 1400 is required to explain the observed coupling constant. This yields a minimum free energy dif- ference between 58 and_4g of about 2 kcal./mole. 72 Whereas the enthalpy difference between 58 and 40 of N-ethyl acetaldimine is at least 2.0 kcal./mole (based on N-cyclohexyl acetaldimine), that between 41 and 42 is about H H H H \ \/ c/ c H CH3 H/ H’ CH3 H 41 42 zero. The non-bonded energies calculated from the data of Table XXIII and summarized in Figure 10, point to non-bonded interactions between H1 and H6 in 45 as the source of this difference. X,/C\C/H ll “:\Hs° R/C\Hl H6 Table XXVII compares the trans-five—bond coupling con- stants for gyn—N-methyl QHmethyl ketimines and those of the analogous N-methyl aldimines. For both, substitution of a 1 methyl group for an QHproton trans to the N-methyl group pro— duces little difference in the coupling constants; but, when a second deroton is replaced by a methyl, the coupling con- stants decrease sharply. By reason of analogy, the conform- ations about the bond joining the trans-Obcarbon to the tri~ gonal carbon of the ketimines must be similar to those about the bond joining the correSponding carbons of aldimines. EXPERIMENTAL 1. Reagents Most aldehydes and ketones used were commercially avail- able. EfButylacetaldehyde was prepared by the method of Brown and Tsukamato (56) from N,N-dimethyl t—butylacetamide. The amide was prepared by addingt7116 g. (0.55 mole) of Efbutylacetyl chloride (b.p. 128-1510, Aldrich Chemical Co., Inc.) to an excess of 25% aqueous dimethylamine. The amide was extracted with benzene, dried with potassium carbonate and distilled, b.p. 78-790 at 6 mm.; 41.6 g. (0.29 mole, 55% yield) of the amide was obtained. To a complex prepared by adding 15.2 g. (0.15 mole) of ethylacetate to 5.80 g. (0.1 mole) of lithium aluminum hydride (Metal Hydrides, Inc.) in approximately 150 ml. of dry ether, 14.5 g. (0.1 mole) of the amide in 70 ml. of dry ether was added dropwise at 00, under a nitrogen atmOSphere. After the adduct was stirred for an hour at 00 and then refluxed for fifteen minutes, it was hydrolyzed with 5N sulfuric acid. The etheral fraction was removed, washed with 5% bicarbonate solution, washed with water, dried over magnesium sulfate, and distilled; 1.9 g. (0.02 mole, 20% yield) was collected at 100-1040. All amines used were commercially available. Methylamine was used either as the 55% aqueous solution or was condensed from the gas. 75 74 2. Preparation of Schiff Bases Schiff bases were prepared from the carbonyl reagents and amines by established methods (57-62). After mixing the reagents at temperatures between —50 and 00, the solution was saturated with potassium or sodium hydroxide and the imine fraction was collected. The residual water was removed by storing the imine fraction overnight in a sealed container with either molecular sieves, type 4-a (Fisher Schentific Co.), or a basic drying agent: potassium hydroxide, sodium hydroxide, barium oxide, magnesium sulfate, or potassium carbonate. They were purified either by distillation, or by gas chromatography using a Perkin-Elmer Vapor Fractometer equipped with a nine foot 20% SF—50 Silicon preparative column. Tables XXVI to XXIX list their boiling points. Typical preparations are described below. N-methyl acetaldimine. To 5.9 g. (0.19 mole) of methyl- amine (neat) maintained at approximately —500 in a dry ice— isopropyl alcohol bath, 7.5 g. (0.17 mole) of acetaldehyde was added dropwise with stirring. At the completion of ad— dition, the solution was warmed to 00 and potassium hydroxide was added until two layers appeared. The aqueous phase was removed, and the organic portion was left with anhydrous potassium carbonate overnight. Distillation at approximately room temperature yielded the imine. Since its n.m.r. spectrum contained Spurious peaks, the aldimine was further purified by gas chromatography as mentioned above. 75 Table XXVI. Boiling Points of N-Methyl Aldimines Methylimine of Observed Literature.a Acetaldehyde 24° 27.50 Propionaldehyde 49-500 52.50 Butyraldehyde 74-75O 81° Valeraldehyde 40-460 (100 mm.) Heptaldehyde 71—750 (20 mm.) Isovaleraldehyde 99-102O QHEthylhexylaldehyde 86-870 (54 mm.) aReference 62. Table XXVII. Boiling Points of Nit-Octyl Aldimines EfOctylimine of Observed Acetaldehyde 66-750 (58 mm.) Propionaldehyde 94-1040 (75 mm.) QbEthylhexylaldehyde 119-1260 (2 mm.) Table XXVIII. Boiling 76 Points of N-Alkyl Acetaldimines Acetaldimine of Observed Literature a Methylamine 240 27.50 Ethylamine 40-440 480 .n-Propylamine 65-690 740 _i§g-Propylamine 46-560 590 nfButylamine 91—970 1020 isngutylamine 89-91O 'n-Pentylamine .119-127O 5-Pentylamine 100-109O Cyclohexylamine Benzylamine 89—950 (82 mm.) 72-850 (7 mm.) 940 (21 mm.) a Reference 57. Table XXIX. Boiling Points of N-Methyl Ketimines Methylimine of Observed Literature a Butanone 82-86O Methylbutanone 105.50 580 (158 mm.) Pinacolin 109-110O 5~Pentanone 108-1110 1150 aReference 59. 77 N—methyl cyclohexanecarboxaldimine. To approximately 2 g. (0.06 mole) of methylamine (neat) maintained at —500, 2.55 g. (0.02 mole) of cyclohexanecarboxaldehyde (K and K Laboratories) was added dropwise with stirring. The mixture was warmed to 00 and approximately 5 g. of potassium hydroxide was added. After gas evolution ceased, the organic liquid was decanted into a bottle containing mo1ecular sieves, type 4—a, and left overnight. .The aldimine was suitable for use without further purification. N-methyl valeraldimine. To 40 ml. (23. 12 g., 0.4 mole) of 55% aqueous methylamine maintained at 00, 10 g. (0.12 mole) of valeraldehyde was added dropwise with stirring. Potassium hydroxide was added drOpwise with stirring. Potassium hydroxide was added until two layers were evident. The organic layer was removed and left overnight with barium oxide. The imine distilled from 40 to 460 at 100 mm. Nfigroctyl propionaldimine. To 11.6 g. (0.2 mole) of propionaldehyde maintained at 00, 25.8 g. (0.2 mole) of 'E-octylamine was added dropwise with stirring. Potassium hydroxide was added until the organic and aqueous phases separated. The organic layer was isolated and left overnight with potassium hydroxide. The imine distilled from 97 to 104° at 75 mm. N-propyl acetaldimine. To 9.8 g. (0.22 mole) of acetal- dehyde maintained at approximately ~200, 9.9 g. (0.17 mole) of n—propylamine was added dropwise with stirring. The 78 mixture was warmed to 00, and then potassium hydroxide was added until two layers were evident. The organic layer was isolated and then left overnight with barium oxide. The imine distilled from 65 to 690. N-methyl ethyl methyl ketimine. To 60 ml. (pg. 24 g., 0.8 mole) of 55% aqueous methylamine maintained at 00, 14.4 g. (0.2 mole) of butanone was added dropwise with stirring. After addition was completed, the mixture was stirred for three hours at room temperature. Then potassium hydroxide was added until two layers appeared. The crude organic material was left with barium oxide for one week. It was fractionated on a 15" Nester & Faust Spinning band column; the fraction which distilled from 82 to 860 was collected and used. Attempted preparations of Nfiteoctyl dimethyl ketimine. A mixture of 25 g. of acetone (0.45 mole), WhiCh had been dried over magnesium sulfate, and 15 g. of p—octylamine (0.1 mole) was left over anhydrous calcium sulfate for a three month period. Analysis of the mixture at various intervals by gas chromatography using an Aerograph Model A90~P Gas Chromatograph equipped with a 20 foot carbowax column showed only the original starting materials. A mixture of 25.2 g. (0.4 mole) of acetone, 25.8 g. (0.2 mole) of E-octylamine, and 100 ml. of benzene was refluxed for three days. Gas chromatographic analysis by the same means as described above showed only starting materials. ‘1— 79 5. Attempted Preparation of N-Methyl Formaldimine Hexahydro-1,5,5-trimethyljg-triazine, (CH3NCH2)3, was prepared by adding 48 ml. (0.5 mole) of 55% aqueous methyl— amine to 40 ml. of 40% aqueous formaldehyde maintained at 00. Potassium hydroxide was added until two layers appeared. The organic layer was isolated and left overnight over crushed potassium hydroxide. Distillation provided 17.9 g. (81% yield) of the triazine, b.p. 87-890 at 20 mm. Its n.m.r. Spectrum showed singlets at T = 6.89 and 7.78 p.p.m. in a 2.5 ratio. The triazine was pyrolyzed by passing it through a U—tube packed with fused silica—alumina (1:1 by mole) maintained at approximately 440-4400 and 0.2 mm. (65,64). The system was equipped with a dry ice—isopropyl alcohol trap to collect un— reacted trimer and traces of water and a liquid nitrogen trap to collect the monomeric imine. The collected monomer was distilled under vacuum into an n.m.r. tube kept in an ethanol slush trap (approximately -1000); in one attempt pentane was used as a solvent in the n.m.r. tube. However, in all attempts the n.m.r. spectrum, taken at ~500, failed to exhibit the peaks expected of the monomer. In addition to the above trimer, peaks indicative of two other materials were observed. One exhibited singlets at T = 6.68 and 7.67 p.p.m. (ratio of 2:5) and the other showed singlets at 6.95 and 7.67 p.p.m. (ratio of 2:5). 80 4. Nuclear Magnetic Resonance Spectra ‘All n.m.r. Spectra were determined at 60 Mc on a Model A-60 Spectrometer (Varian Associates) on undegassed samples. Tetramethylsilane was used as the internal reference standard (assigned T = 10.00 p.p.m.). Chemical Shifts were measured using sweep widths of 500 and 250 c.p.s. Spin-spin coupling constants and isomer chemical Shift differences (A5 values) were measured from spectra of 50 c.p.s. sweep widths. To in- sure that no internal changes from day to day in the n.m.r. Spectrometer affected the results, chemical shift data were correlated with the chemical shifts of the pinacolin protons (5 = 67.0 and 124.0 c.p.s.), and Spin-Spin coupling constants were correlated with the vicinal coupling constant of the acetaldehyde quartet (J = 2.85 c.p.s.). Temperature control at temperatures other than 560 was achieved with a Varian N.M.R. Variable Temperature Controller. These temperatures were checked using the chemical shift dif- ferences between the hydroxyl and methyl protons of methanol at temperatures below 560 and between the hydroxyl and methylene protons of ethylene glycol at temperatures above 560. The temperatures are accurate to.i5o. 5. Solvents Acetonitrile, carbon tetrachloride, cyclohexane, and benzene were purified from commercially available reagents by standard procedures (65). Dimethyl sulfoxide was obtained from Crown Zellerback Corp. and purified by distillation from 81 calcium hydride (66). Benzene-d6 was obtained from Merck, Sharpe & Dohme of Canada, Ltd. 6. Attempted Isomerization of N-Methyl Acetaldimine Dimsyl sodium was prepared by the method of Corey and Chaykowski (66). The apparatus consisted of a 50 ml. round bottomed flask, equipped with a side arm covered by a rubber septum and attached through its condenser to a three-way stopcock. The flask was charged with 2.41 g. (0.05 mole) of 52.8% sodium hydride on mineral oil. After it was washed three times with dry pentane, the flask was evacuated by aspirator and flushed with dry nitrogen by means of the three— way stopcock. The aspirator was then removed from the threem way stopcock and replaced by a mercury sealed U-tube. After again flushing the system with dry nitrogen, 25 ml. of DMSO was added with a hypodermic syringe. The mixture was mag- netically stirred and heated at 65-700. After one-half hour the liquid turned yellowish-gray and gas evolution ceased. The solution was heated for an additional fifteen minutes, for a total heating time of forty-five minutes. After cooling to room temperature, 15 ml. (pa. 0.25 mole) of N—methyl acetaldimine was added by syringe in a thirty second period. 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