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Chiroptical properties of 2-substituted piperidines
CHIROPTICAL PROPERTIES OF 2-SUBSTITUTED PIPERIDINES A SIMPLE HELICITY RULE’ J. CYMXMANCRAIG,+S.-Y. CATHERINELEE and W. E. Pruztlu. Jr. Departmentof Pharmrceutkl Chemistry. Schoolof Pbumrcy, University of CJifornia. San Francisco.CA 94143. U.S.A.
and H. C. BEYERMAN and L. MMT Laboratoryof OrganicCk.mhtry.fccbnischeHgscbool. Delk The Netherlands (Received in USA 2 Amp.s~ Wll; ReceiDadia UK for pablicatior
31 August 1977)
A&&&-The CD spectra of lUteen 2-rubstitutedpip&dines 2 md their N-matbyked derivatives 1 have been determined.The sign of the Cotton effect observedfor the MU* transitionof nitrogenis shownIO be conelated. for a given absolute co-n. with tbe axial or quatorLl orientation of the nitrogen lone prir. and to be detmmioedby the screw senseof the Micity betweenI& nitrogenlone pair and the 2-substituenfR in I unf 2: for compoundsof the absoluteDcon&nation. a positive belicity gives a positive CD md vice versa.
in the Fischer protection lb. Since the n+o* transition rquires the presence of a lone pair of electrons on nitrogen. the CD in every case vanished completely on protoaation. Measurements were made in 95% alcohol and (in a few cases) also in cyclohexanc. The alcohol la. R- n-(CHz),,OH is derived from the macrocyclic spcrmidine alkaloid oncinotin’ 3 and was employed to assign the absolute cou6guration of 3 as L by chiroptical correlation with I-methylconiinc. It had been demonstrated earlier” that the OH function did not interfere in this assignment.
Tk longest wavekngth transition of saturated aliphatic and heterocyclic amines is the n + ti transition involving a nonbonding orbital of nitrwn and the u* orbital of the C-N bond. This transition, which is kcatal near 200 MI. disappears on protonation” Early ORD’ measurements on coniinc and 2-tnathylpipcridine showed that the n-+ u* transition of pip&dines is optically active, and sub sequent work on the absolute configuration of several pipcridinc alkaloids5 demonstrated for the llrst time that the Cotton effect (C.E.) of the n-u* transition of nitrogen could bc observed directly by CD. The ptB&?nt study reports the CD spectra of fifteen optically active 2-substituted pipcridiues 2a and their N-Me derivatives la. and a simple helicity rule.
lj
mwLTsAND-
Tk CD data for 15 pip&dines are given in Tables 1 and 2. Tksc include 8 number of natural products‘ and their N-Me derivatives. All the compounds listed in Tabks 1 and 2 arc rclatcd to ~pipocohc acid, as shown sol
Lie the n+a* transition of the CO chrDmOphOrC, the n + u+ transition of nitrogen shows a prominent blue shift of about 20nm on going from a non-polar (cyclokxane) to a polar (95% alcohol) solvent, with a concomitant dccrcase in intensities (Fig. I). In the case of tha n+ w+ transition, the polar solvent tends to stabilize the nonbonding orbital more than the antibonding orbital, resulting in a blue shift of the spectrum,’ and the same argument may k applied to the n + u* transition of the cyclic amincs 1 and 2. The markedly enhanced CD intensity observed (Table 2) for Zmcthyl- and 2cthylpipcridinc (Fig. 1) in cycle hexanc vs alcohol solution may be due to increased intermokcular H-bonding in the nonpolar solvent for tksc -NH compounds since this change does not seem
T&k
1. Circular dichiim
D-~+l-l-~th~lpipeclioo (0)
c33
D-w-l-atbyl-2ltbylpiperidfm
c2%
(S)
.*
of N-methyl pipdines
la
cP5
~(+)-l-neh~leailrt
(6)
"-vt
N4.P
+3110
2001
P(+)-l-nmbylpipmcollool
(1)
a20u
+14.7'
+1ODO
2001
o-iaf2~lloB
+21'
+43DO
1971
D-(+)-l-rktbyl-2(ll'-bydror)mtd~cyl)ptprrldiw= (6)
T&k 2. Circulu dichroirm of NH pip&ii
(5)
CBlr
(8;)
a3
P(+)-2-m+piperidi&
D-(+whlffw
(6)
+7.39
h
+4b10
#O?Sb -730
205
+1&.9*b
-mob
227
m'c3E7
+3.0*
-630
205
“-v9 CBZOR
+7.5*
-MO
204
-16.9.
-1140
200
9%~
+2.3'
-690
203
-27.P
-SlO
205
czar
#A*
c2%
D-(+)-2-o-Bu~l plpwidiwc
D-6I-?fpw.olimol B-(+)-2-(2'Eydroxyet$l)pipwidim
(S) (1)
D-(-)-Sedridimm
tu_cetcacoe,cn,
D-(+)-Allwmdrldirw
mai2ai(on)pI,
+17*0*
-933
205
P(-)-cimhflri~
m)-clNoa)c21#
-9.3'
-1917
19a
D-c-)-klwPilm
mcn,cu(0s)c,R,
-19.5.
209
Chiroptical prop&es of 2.substituted pip&dines
503
H-bonding from the OH of the o-OH substituted sidechain R to the amino group is probably responsible for the blue shift of the CD maximum (cc. 5 nm). This may be caused by the lowering of the ground state energy of the nonbondinp orbital of nitrogen. The gteater r@dity of the H-bonded structure also results in an increased value of the cllipticity for these two compounds. The most favored conformation for the 2-substituted NH pip&dines 2 will be that with an NH axial pnfcrence and an equatorial electron pair (Rig. 3). As in
B
-moo
-2000
i_ A
Fu. 1.CD spean of o-(+)-241ytpip&& and cycJobcxule(-).
in 95%ethanol(---)
to occur in the corresponding N-methyl-2cthylpiperidine (Table I). It has been established by NMR’ and several other physical methods” that the pip&d& system exists in a nearly perfect cyclohexane chair conformation. Two processes may be operative in this system: ring reversal and inversion of nitrogen. As the proton NMR spectrum of piperid&3JJsd4 consists of two fairly sharp peaks at temperatures above -lo”, both processes must be fast on the NMR time scale.” For 2.alkylsubstituted pip&tines of both types I and 2, the a-substituents are generally assumed to occupy the equatorial position in order to minimixe steric interactions between the neighboring tin8 sub&tents. This has been continned by several studies using both ‘H NMR12and “C NMR,‘%” and the same has been shown ~~~~~~~~~.~~.,~~~~~b~~~~
zet;
methods that the Me group in N-methytpiperidines has a decided preference for the quatorial position, with an axial lone pair of ekctrons as shown in Fii 2. where the Newman projection is drawn looking at the asymmetric center and along the C-N bond. All the N-methytpiperidines shown in Table 1 have a positive C.E. below 20Onm. Although the maximum could not be reached in 95% alcohol solution, use of cyclohexane as solvent made it possible to observe the CD maximum at 204~1 for the I-methyl-241~1 compound. Assuming a solvent shift of co. 20 nm; this would place the CD maximum in alcohol at co. 185nm. in ageement with the fact that this CD maximum was not reached at 188run. Table 2 gives the CD data for the compounds of type 2 possessing an NH group. These [with the exception of u-(+)-pipecotine (2, R= Me)] show a negative C.E. with a maximum at co. 205 run Usb cyclohexane, a similar solvent shift (cc. 20 nm) to longer wavelen8ths (227 nm) was observed for the 2.Et compound. In the case of D4-)-pipecolinol and u+)-conhydrine, intramolecular
li
ii
Fig 2. Newmanprojectionof 1.
Ii
Fu. 3. Newmanprojectionof 2. pip&dine itself’0 this form is favored both by the gauche e&P (the axial conformation maximixins the number of gauche interactions between the equatorial lone pair on N and the vicinal polar C-H bonds) and by attractive 1,3-axial N-H interactions.” However, in ~-MC substituted piperidines. “C NMR evidetlcP‘ indicates that both 2,b ad 2,Sdimethylpiperidine, and 2-methylpiperidine, possess an quatorial ~-MC pup and an axial electron pair, as in quinolixidine.’ 3LNo reasonable explanation of this anomaly has been advanced. The chiroptical properties of u-(+)-pipecoline appear to confirm the NMR evidence. Not only does its CD have the opposite sign (Table 2). but also the CD maximum is shifted to shorter wavelengths (below 190nm) in alcohol solution. This blue shift was also apparent in cyclohexane. It therefore appears to be the only compound in Table 2 which resembks in its CD proper&s the 13disubstituted compounds of type 1 (Tabk 1). It should be noted that its N-nitroso derivative shows similar CD behavior (sign of C.E. apposite to that of all other a-substituted N-nitroso compounds of the same con6gmation).‘9 If compound 2, R= Me possesses an axial electron pair, it thereby falls into the group of 2-substituted pip&lines shown in Fig. 2. explaining why its CD spectrum conforms in sign and wavelength with those shown in Table I. The CD maximum of 2.alkylpiperidincs with an quatorial electron pair 2 is thus generally found at higher wavelength (205nm) than that of those with an axial electron pair 1 (<2@I nm). This also applies to 2-methylpip&dine which from other evidence is thought to have an axial electron pair, and in which A, is <2OOnmfor the CD. Although this means that the energy difference behveen the non-bonding orbital of nitrogen and the anti-bonding orbital of the C-N bond is gteater for the n-, u* transition of that conformation in which the electron pair is axial compared with that in which the ekctron pair is equatorial, no theoretical interpretation of this fact is available. Comparing Fw. 2 and 3. it can be seen that the nlative positions of the lone pair electrons and the a-substituent R are opposite for the two cases. In Fu. 2. if one draws an arrow from the lone pair to the 0. substituent, using the pathway with smaller dihedral angle, it traces out a clockwise (positive) screw sense, while in Fe. 3, it produces a counter clockwise (negative) screw sense. EmpiricaUy, for compounds of
absolute tbconflguration, these screw senses may be
‘L. W. Pickett, hf. E. Comb&, G. M. Wiier, D. A. Semenov
correlatedwith the signs of &e Cotton effect, i.e. a clockwise screw sense of the helicily indicatinga positive Cotton effect, and a counterclockwise screw sensea
end J. hf. Buckkv. J, Am. Cb Sot. 75. I618 (1953). *J. C. Craip and S: K. Roy, Tudm Si, 401 il%Sj. ‘H. C. Beyermen, L Maat, J. P. Visser, J. C. Cm@ R P. K. Cbea aad S. K. Boy. Rec. Tmo. Chh. 88.1012 (K&9);0. F&r,
negativeCotton effect.
Itisof interesttha~inspiteof thefactthatcompounds of type 1 and 2 gave oppositely-signed CD maximafor the sumc absolute co&uration (IkbIes 1 and 21, aI1 com~u~s of the L-seriesgive negative plain ORD curves below 22Snm in alcohor” whetherthey are of tw 1 or 2. It shouldbe noted that the ORDcurveof r-(-)-con&e (R) in w&r shows a weak but distinct posit&eC.E. in the #K)nmregion,~0~~ the positive CD~ximum foundat the samewavekngth.PThus, the absoluteconfigurationof t+-t2-ethylpiperidine(RI was correctlyestabiished’9by comparisonof its ORD spectrumwith L_(-)&nethylpiperidine CR)as reference compound.The sign of the CD maximumof 1 and 2 in the 200 MI region,corresponding to the II+ ti transition of nitrogen,is thereforegovernedby the dihedralrelationshipbetween the lone electronpair on N and the a-substituentR, and is relatedto the screwsense of the he&&yin the mannershownabove.Therefore,assuming the preferredequatorialposition of the sidechainR in boihland2,itwiUbetheoxiaiorequatorirlna~of the lone electronpair(i.e. the colophon) which will be the decidingfactor in the helicity and hence in the sign of the CD. While the CD is conformationdependent, the ORDcurve is the resultof the summationof the total (4-b a+) rotationalconaibutionsbelowMOnm. to which the lone pair of N does not contribute significantly,and in alcohol thereforeappearsto be independentof co~o~a~on~ changes.
K. chul, Acfochau.-&luhi-~*-3479 (l%g. ‘H. 0. &tit, Erg&&e da Afkofoid-Ch&e his 1960,p. 125. Akademie-Verlq, Berlii (1961). ‘A. Ou&be~, M, M. Bad& M. Hesse cad H. Scbati& Jfdu. CUm. Acre 67,414 (1970. ‘J. N. Murrell, m T&eoryof the Eiectro& sprctm of &&raic Molcctdu, p. 163.M&ten. Lo&a (863). ‘J. 8. Lambert. I, Am. Chae. Sot. I), 1836(1967). ‘OForsdditjonai refereoces see: J. B. Umbert cod S. 1. Featbermaa, C& Rm 7S, 61I (1975). “1. B. Lamben and R. G. Kc&e.J. Am.f&m Ser.$8, 620 (1964). ‘9. L Hooper sadA.Kanlos,CUR1. CIIUR. 51,4080(1973). ‘H. Bootb end D. V. Grilfltbs. f. Chem. Sot. P&II JI, 842 (1973). “E. L. Eiitl, W, F. Beiky. L D. Kopp, R L. Wilier, D. M. Great. K. Bettram& K. A. Cbristensea. D. K. Da&. M. W. Lhch, E. Weaker& P. hf. !kbcUandfi. W.Co&a& J. Am. them. &c. n, 372 (l??S). “I. Morfshirae, K. Yosbikawe, K. Okada, T. Yonezawa end K. Goto. Ibid.9% 165(19731. “R 0. Let& L. Pet&is, A. F, Ellis aad R K. Jensen, 3. P&s. Ch#rn.74.2816 (1910). “A. 1. Joaes end M. M. A. Hassea. J. @t. Chere. 9,2332 (19)2). “E. L. Eliel and F. W. Viubepper, J. Am. Chem. Sot. 96.2257 “L!? Beyexaua, S, Ven den Bosch J Ii Breaker aad L Maat, Rec. IhaB. chfm. 90,755 (1911);&is. n&t is very puzzl& if ‘N-N / cd-n
The CD and ORD rn~e~a~ were carried out on a RotisseiJouan Me& II dicbrogaph and on a Jasco ORDCM at room temp. CD values are recorded es molecular eilipticity units [S] and sre given only for maxima or the lowest wavekogtha measWcd.
‘ThisPIperforms Part 19 of the series “Gptical Rotetory Disprnioa and Absolute ConQumtion”. ZE. Tannenbaum, E. hf. Cot311and A. 1. Harrison. J. Chem. Phys. 21.3ll(lM3).
(uniikt NH nnd Met exists iti one ietmm&c ‘0 y-N\
_ tIecalm of il&osamiac rcsoasace.
sadcouldiavdvesomek.j4u&y of the N-NO group. ‘Dr. f&samtme, M. T&as4 and M. h&t&i, BuK. C&RI. SIC. 3qmn41,2466 (l%n). “T. Maan~uoe d M. Takasugi. Chcm. COIIIMUR. 265 (1%7). =J. C. C& aad A. R Pinder, uapubWcd work. =D. C. Appkton, J. McKennr, J. M. McKenoa, L B. Sit and A. R Wefley, L Am. Clrmr. scrt. 9@,2!?2(1976). =S. Wolfe, Acct& Chart. Ru. 1.102 (197f). =J. B. tibert, D. S. Beiky sod 8. P. Miibel. 1. Am. Ghan. sot. %,3812 (1972). “H. S. Auoo, C&. k I& 1338(l%n.
and H. C. BEYERMAN and L. MMT Laboratoryof OrganicCk.mhtry.fccbnischeHgscbool. Delk The Netherlands (Received in USA 2 Amp.s~ Wll; ReceiDadia UK for pablicatior
31 August 1977)
A&&&-The CD spectra of lUteen 2-rubstitutedpip&dines 2 md their N-matbyked derivatives 1 have been determined.The sign of the Cotton effect observedfor the MU* transitionof nitrogenis shownIO be conelated. for a given absolute co-n. with tbe axial or quatorLl orientation of the nitrogen lone prir. and to be detmmioedby the screw senseof the Micity betweenI& nitrogenlone pair and the 2-substituenfR in I unf 2: for compoundsof the absoluteDcon&nation. a positive belicity gives a positive CD md vice versa.
in the Fischer protection lb. Since the n+o* transition rquires the presence of a lone pair of electrons on nitrogen. the CD in every case vanished completely on protoaation. Measurements were made in 95% alcohol and (in a few cases) also in cyclohexanc. The alcohol la. R- n-(CHz),,OH is derived from the macrocyclic spcrmidine alkaloid oncinotin’ 3 and was employed to assign the absolute cou6guration of 3 as L by chiroptical correlation with I-methylconiinc. It had been demonstrated earlier” that the OH function did not interfere in this assignment.
Tk longest wavekngth transition of saturated aliphatic and heterocyclic amines is the n + ti transition involving a nonbonding orbital of nitrwn and the u* orbital of the C-N bond. This transition, which is kcatal near 200 MI. disappears on protonation” Early ORD’ measurements on coniinc and 2-tnathylpipcridine showed that the n-+ u* transition of pip&dines is optically active, and sub sequent work on the absolute configuration of several pipcridinc alkaloids5 demonstrated for the llrst time that the Cotton effect (C.E.) of the n-u* transition of nitrogen could bc observed directly by CD. The ptB&?nt study reports the CD spectra of fifteen optically active 2-substituted pipcridiues 2a and their N-Me derivatives la. and a simple helicity rule.
lj
mwLTsAND-
Tk CD data for 15 pip&dines are given in Tables 1 and 2. Tksc include 8 number of natural products‘ and their N-Me derivatives. All the compounds listed in Tabks 1 and 2 arc rclatcd to ~pipocohc acid, as shown sol
Lie the n+a* transition of the CO chrDmOphOrC, the n + u+ transition of nitrogen shows a prominent blue shift of about 20nm on going from a non-polar (cyclokxane) to a polar (95% alcohol) solvent, with a concomitant dccrcase in intensities (Fig. I). In the case of tha n+ w+ transition, the polar solvent tends to stabilize the nonbonding orbital more than the antibonding orbital, resulting in a blue shift of the spectrum,’ and the same argument may k applied to the n + u* transition of the cyclic amincs 1 and 2. The markedly enhanced CD intensity observed (Table 2) for Zmcthyl- and 2cthylpipcridinc (Fig. 1) in cycle hexanc vs alcohol solution may be due to increased intermokcular H-bonding in the nonpolar solvent for tksc -NH compounds since this change does not seem
T&k
1. Circular dichiim
D-~+l-l-~th~lpipeclioo (0)
c33
D-w-l-atbyl-2ltbylpiperidfm
c2%
(S)
.*
of N-methyl pipdines
la
cP5
~(+)-l-neh~leailrt
(6)
"-vt
N4.P
+3110
2001
P(+)-l-nmbylpipmcollool
(1)
a20u
+14.7'
+1ODO
2001
o-iaf2~lloB
+21'
+43DO
1971
D-(+)-l-rktbyl-2(ll'-bydror)mtd~cyl)ptprrldiw= (6)
T&k 2. Circulu dichroirm of NH pip&ii
(5)
CBlr
(8;)
a3
P(+)-2-m+piperidi&
D-(+whlffw
(6)
+7.39
h
+4b10
#O?Sb -730
205
+1&.9*b
-mob
227
m'c3E7
+3.0*
-630
205
“-v9 CBZOR
+7.5*
-MO
204
-16.9.
-1140
200
9%~
+2.3'
-690
203
-27.P
-SlO
205
czar
#A*
c2%
D-(+)-2-o-Bu~l plpwidiwc
D-6I-?fpw.olimol B-(+)-2-(2'Eydroxyet$l)pipwidim
(S) (1)
D-(-)-Sedridimm
tu_cetcacoe,cn,
D-(+)-Allwmdrldirw
mai2ai(on)pI,
+17*0*
-933
205
P(-)-cimhflri~
m)-clNoa)c21#
-9.3'
-1917
19a
D-c-)-klwPilm
mcn,cu(0s)c,R,
-19.5.
209
Chiroptical prop&es of 2.substituted pip&dines
503
H-bonding from the OH of the o-OH substituted sidechain R to the amino group is probably responsible for the blue shift of the CD maximum (cc. 5 nm). This may be caused by the lowering of the ground state energy of the nonbondinp orbital of nitrogen. The gteater r@dity of the H-bonded structure also results in an increased value of the cllipticity for these two compounds. The most favored conformation for the 2-substituted NH pip&dines 2 will be that with an NH axial pnfcrence and an equatorial electron pair (Rig. 3). As in
B
-moo
-2000
i_ A
Fu. 1.CD spean of o-(+)-241ytpip&& and cycJobcxule(-).
in 95%ethanol(---)
to occur in the corresponding N-methyl-2cthylpiperidine (Table I). It has been established by NMR’ and several other physical methods” that the pip&d& system exists in a nearly perfect cyclohexane chair conformation. Two processes may be operative in this system: ring reversal and inversion of nitrogen. As the proton NMR spectrum of piperid&3JJsd4 consists of two fairly sharp peaks at temperatures above -lo”, both processes must be fast on the NMR time scale.” For 2.alkylsubstituted pip&tines of both types I and 2, the a-substituents are generally assumed to occupy the equatorial position in order to minimixe steric interactions between the neighboring tin8 sub&tents. This has been continned by several studies using both ‘H NMR12and “C NMR,‘%” and the same has been shown ~~~~~~~~~.~~.,~~~~~b~~~~
zet;
methods that the Me group in N-methytpiperidines has a decided preference for the quatorial position, with an axial lone pair of ekctrons as shown in Fii 2. where the Newman projection is drawn looking at the asymmetric center and along the C-N bond. All the N-methytpiperidines shown in Table 1 have a positive C.E. below 20Onm. Although the maximum could not be reached in 95% alcohol solution, use of cyclohexane as solvent made it possible to observe the CD maximum at 204~1 for the I-methyl-241~1 compound. Assuming a solvent shift of co. 20 nm; this would place the CD maximum in alcohol at co. 185nm. in ageement with the fact that this CD maximum was not reached at 188run. Table 2 gives the CD data for the compounds of type 2 possessing an NH group. These [with the exception of u-(+)-pipecotine (2, R= Me)] show a negative C.E. with a maximum at co. 205 run Usb cyclohexane, a similar solvent shift (cc. 20 nm) to longer wavelen8ths (227 nm) was observed for the 2.Et compound. In the case of D4-)-pipecolinol and u+)-conhydrine, intramolecular
li
ii
Fig 2. Newmanprojectionof 1.
Ii
Fu. 3. Newmanprojectionof 2. pip&dine itself’0 this form is favored both by the gauche e&P (the axial conformation maximixins the number of gauche interactions between the equatorial lone pair on N and the vicinal polar C-H bonds) and by attractive 1,3-axial N-H interactions.” However, in ~-MC substituted piperidines. “C NMR evidetlcP‘ indicates that both 2,b ad 2,Sdimethylpiperidine, and 2-methylpiperidine, possess an quatorial ~-MC pup and an axial electron pair, as in quinolixidine.’ 3LNo reasonable explanation of this anomaly has been advanced. The chiroptical properties of u-(+)-pipecoline appear to confirm the NMR evidence. Not only does its CD have the opposite sign (Table 2). but also the CD maximum is shifted to shorter wavelengths (below 190nm) in alcohol solution. This blue shift was also apparent in cyclohexane. It therefore appears to be the only compound in Table 2 which resembks in its CD proper&s the 13disubstituted compounds of type 1 (Tabk 1). It should be noted that its N-nitroso derivative shows similar CD behavior (sign of C.E. apposite to that of all other a-substituted N-nitroso compounds of the same con6gmation).‘9 If compound 2, R= Me possesses an axial electron pair, it thereby falls into the group of 2-substituted pip&lines shown in Fig. 2. explaining why its CD spectrum conforms in sign and wavelength with those shown in Table I. The CD maximum of 2.alkylpiperidincs with an quatorial electron pair 2 is thus generally found at higher wavelength (205nm) than that of those with an axial electron pair 1 (<2@I nm). This also applies to 2-methylpip&dine which from other evidence is thought to have an axial electron pair, and in which A, is <2OOnmfor the CD. Although this means that the energy difference behveen the non-bonding orbital of nitrogen and the anti-bonding orbital of the C-N bond is gteater for the n-, u* transition of that conformation in which the electron pair is axial compared with that in which the ekctron pair is equatorial, no theoretical interpretation of this fact is available. Comparing Fw. 2 and 3. it can be seen that the nlative positions of the lone pair electrons and the a-substituent R are opposite for the two cases. In Fu. 2. if one draws an arrow from the lone pair to the 0. substituent, using the pathway with smaller dihedral angle, it traces out a clockwise (positive) screw sense, while in Fe. 3, it produces a counter clockwise (negative) screw sense. EmpiricaUy, for compounds of
absolute tbconflguration, these screw senses may be
‘L. W. Pickett, hf. E. Comb&, G. M. Wiier, D. A. Semenov
correlatedwith the signs of &e Cotton effect, i.e. a clockwise screw sense of the helicily indicatinga positive Cotton effect, and a counterclockwise screw sensea
end J. hf. Buckkv. J, Am. Cb Sot. 75. I618 (1953). *J. C. Craip and S: K. Roy, Tudm Si, 401 il%Sj. ‘H. C. Beyermen, L Maat, J. P. Visser, J. C. Cm@ R P. K. Cbea aad S. K. Boy. Rec. Tmo. Chh. 88.1012 (K&9);0. F&r,
negativeCotton effect.
Itisof interesttha~inspiteof thefactthatcompounds of type 1 and 2 gave oppositely-signed CD maximafor the sumc absolute co&uration (IkbIes 1 and 21, aI1 com~u~s of the L-seriesgive negative plain ORD curves below 22Snm in alcohor” whetherthey are of tw 1 or 2. It shouldbe noted that the ORDcurveof r-(-)-con&e (R) in w&r shows a weak but distinct posit&eC.E. in the #K)nmregion,~0~~ the positive CD~ximum foundat the samewavekngth.PThus, the absoluteconfigurationof t+-t2-ethylpiperidine(RI was correctlyestabiished’9by comparisonof its ORD spectrumwith L_(-)&nethylpiperidine CR)as reference compound.The sign of the CD maximumof 1 and 2 in the 200 MI region,corresponding to the II+ ti transition of nitrogen,is thereforegovernedby the dihedralrelationshipbetween the lone electronpair on N and the a-substituentR, and is relatedto the screwsense of the he&&yin the mannershownabove.Therefore,assuming the preferredequatorialposition of the sidechainR in boihland2,itwiUbetheoxiaiorequatorirlna~of the lone electronpair(i.e. the colophon) which will be the decidingfactor in the helicity and hence in the sign of the CD. While the CD is conformationdependent, the ORDcurve is the resultof the summationof the total (4-b a+) rotationalconaibutionsbelowMOnm. to which the lone pair of N does not contribute significantly,and in alcohol thereforeappearsto be independentof co~o~a~on~ changes.
K. chul, Acfochau.-&luhi-~*-3479 (l%g. ‘H. 0. &tit, Erg&&e da Afkofoid-Ch&e his 1960,p. 125. Akademie-Verlq, Berlii (1961). ‘A. Ou&be~, M, M. Bad& M. Hesse cad H. Scbati& Jfdu. CUm. Acre 67,414 (1970. ‘J. N. Murrell, m T&eoryof the Eiectro& sprctm of &&raic Molcctdu, p. 163.M&ten. Lo&a (863). ‘J. 8. Lambert. I, Am. Chae. Sot. I), 1836(1967). ‘OForsdditjonai refereoces see: J. B. Umbert cod S. 1. Featbermaa, C& Rm 7S, 61I (1975). “1. B. Lamben and R. G. Kc&e.J. Am.f&m Ser.$8, 620 (1964). ‘9. L Hooper sadA.Kanlos,CUR1. CIIUR. 51,4080(1973). ‘H. Bootb end D. V. Grilfltbs. f. Chem. Sot. P&II JI, 842 (1973). “E. L. Eiitl, W, F. Beiky. L D. Kopp, R L. Wilier, D. M. Great. K. Bettram& K. A. Cbristensea. D. K. Da&. M. W. Lhch, E. Weaker& P. hf. !kbcUandfi. W.Co&a& J. Am. them. &c. n, 372 (l??S). “I. Morfshirae, K. Yosbikawe, K. Okada, T. Yonezawa end K. Goto. Ibid.9% 165(19731. “R 0. Let& L. Pet&is, A. F, Ellis aad R K. Jensen, 3. P&s. Ch#rn.74.2816 (1910). “A. 1. Joaes end M. M. A. Hassea. J. @t. Chere. 9,2332 (19)2). “E. L. Eliel and F. W. Viubepper, J. Am. Chem. Sot. 96.2257 “L!? Beyexaua, S, Ven den Bosch J Ii Breaker aad L Maat, Rec. IhaB. chfm. 90,755 (1911);&is. n&t is very puzzl& if ‘N-N / cd-n
The CD and ORD rn~e~a~ were carried out on a RotisseiJouan Me& II dicbrogaph and on a Jasco ORDCM at room temp. CD values are recorded es molecular eilipticity units [S] and sre given only for maxima or the lowest wavekogtha measWcd.
‘ThisPIperforms Part 19 of the series “Gptical Rotetory Disprnioa and Absolute ConQumtion”. ZE. Tannenbaum, E. hf. Cot311and A. 1. Harrison. J. Chem. Phys. 21.3ll(lM3).
(uniikt NH nnd Met exists iti one ietmm&c ‘0 y-N\
_ tIecalm of il&osamiac rcsoasace.
sadcouldiavdvesomek.j4u&y of the N-NO group. ‘Dr. f&samtme, M. T&as4 and M. h&t&i, BuK. C&RI. SIC. 3qmn41,2466 (l%n). “T. Maan~uoe d M. Takasugi. Chcm. COIIIMUR. 265 (1%7). =J. C. C& aad A. R Pinder, uapubWcd work. =D. C. Appkton, J. McKennr, J. M. McKenoa, L B. Sit and A. R Wefley, L Am. Clrmr. scrt. 9@,2!?2(1976). =S. Wolfe, Acct& Chart. Ru. 1.102 (197f). =J. B. tibert, D. S. Beiky sod 8. P. Miibel. 1. Am. Ghan. sot. %,3812 (1972). “H. S. Auoo, C&. k I& 1338(l%n.