Syntheses, binding properties, and structures of seven new hemicarcerands each composed of two bowls bridged by three tetramethylenedioxy groups and a fourth unique linkage

J . Org. Chem. 1996, 61, 9323-9339

9323

Syn th eses, Bin d in g P r op er ties, a n d Str u ctu r es of Seven New

Hem ica r cer a n d s Ea ch Com p osed of Tw o Bow ls Br id ged by Th r ee

Tetr a m eth ylen ed ioxy Gr ou p s a n d a F ou r th Un iqu e Lin k a ge^1,2

J uyoung Yoon, Chimin Sheu, K. N. Houk, Carolyn B. Knobler, and Donald J . Cram*

Department of Chemistry and Biochemistry, University of California at Los Angeles,

Los Angeles, California 90095

Received J uly 8, 1996^X

Treatment of 2 mol of the bowl-shaped tetrol 1 (derived originally from resorcinol and dihydrocin-

namaldehyde) with 3 mol of TsO(CH₂)₄OTs gave diol 2. Eight compounds with different

combinations of bridges were formed from 2 by treatment with Cs₂CO₃and the following reagents

in the presence of potential guests to give either free or complexed hemicarcerands as follows:

ClCH₂Br gave 4; TsO(CH₂)₂OTs gave 5; TsO(CH₂)₃OTs gave 6; MsO(CH₂)₄OMs gave 7, a known

system; MsO(CH₂)₅OMs gave 8; 2,3-bis(bromomethyl)quinoxaline gave 9; 1,3-(ClCH₂)₂C₆H₄gave

10; 2,6-bis(chloromethyl)pyridine gave 11. Thirty-six fully characterized new hemicarceplexes are

reported which were prepared either directly from diol 2 by the “sealing in” of the guest during

introduction of the fourth bridge, or by guest exchange driven by mass law at 25 to 160 °C. The

guests ranged in size from CHCl₃to 1,2,3-(MeO)₃C₆H₃. The incarcerated guests correlated with

portal sizes of their hosts. Crystal structures of 8.4-MeC₆H₄OMe and 10.CHCl₃were determined.

1

Changes in chemical shifts in H NMR spectra of incarcerated and free guests are interpreted in

terms of their locations in the hosts’ inner phases. The length and nature of the unique host bridge

affects the chemical shifts of the other bridges. Force field calculations of structural models for

N-methylpyrrolidinone incarcerated in 4-7 were made. Approximate half-lives for decomplexation

were determined for complexes involving the larger hosts and guests. Force-field calculations were

made of binding energies and activation energies for decomplexations of models of 7.N-

methylpyrrolidinone, 8.N-methylpyrrolidinone, and 10.N-methylpyrrolidinone. The activation

energies for decomplexation were dissected into intrinsic and constrictive components.

In tr od u ction

method of complexation had the additional synthetic

advantage that the fourth bridge could be the same

(leading to 7⁴) or different than the first three, as in 4-6

and 8-11. In this manner 3 was prepared, which was

found to complex potassium picrate, the picrate ion being

incarcerated but the K⁺being ligated by the six oxygens

of the fourth bridge.⁴

We report here the syntheses and study of new host

systems 4-6 and 8-11 from diol 2 and appropriate

dihalides, ditosylates, or dimesylates in the presence of

Cs₂CO₃and potential guests.

Prior publications on hemicarceplexes involved the

assembly of many hosts by the four-fold bridging of two

bowl-shaped cavitands such as 1 with groups, all four of

which were the same. Variation in the lengths and sizes

of these groups and the sizes of guests controls the

propensity for complex formation and their stabilities in

solution. Hemicarceplexes were prepared by guest-

templation of the shell closures, or by heating empty

hosts with potential guests as solvent. A third method

involves heating hosts or unstable complexes with large

excesses of new guests in high-boiling solvents whose

molecules are too large to enter or occupy the inner

phases of hosts.³A fourth method was described, in

which 2 containing three (CH₂)₄bridging groups was

prepared (30-40% yields) from 1, making use of the fact

that the rate of introducing the fourth bridge leading to

the host is slower than those rates for the first three.

The fourth bridge was introduced in the presence of large

excesses of guests that, in certain cases, were too big or

unstable to provide complexes made by the other three

methods.⁴For example, 7.O(CH₂CH₂)₂NCHO was pre-

pared from 2 and MsO(CH₂)₄OMs in (Me₂N)₃PO (HMPA)

containing O(CH₂CH₂)₂NCHO. This “sealing in of guest”

Resu lts a n d Discu ssion

Syn th eses. Diol 2 was prepared in 40% yield from 1

and 3 equiv of MsO(CH₂)₄OMs in a mixture of Cs₂CO₃

and NMP⁵at 25 °C for 18 h.³This material served as

starting material for the syntheses of the seven new host

systems in which the fourth bridge (R of 4-6, 8-11)

differs from the three (CH₂)₄bridges of 2. Chart 1

summarizes the reagents, reaction conditions, solvents,

product structures, and yields for these shell closures.

The four aprotic dipolar solvents used were NMP,⁵

DMSO, DMA,⁵and HMPA. Bridge donor groups and

products were as follows: CH₂BrCl led to 4.NMP,

4.DMSO, and 4.DMA; TsOCH₂CH₂OTs gave 5.NMP,

5.DMSO, and 5.DMA; TsO(CH₂)₃OTs provided 6.NMP,

6.DMSO, 6.DMA, and empty 6 (HMPA as solvent);

MsO(CH₂)₄OMs gave 7⁶(HMPA as solvent); MsO(CH₂)₅-

^XAbstract published in Advance ACS Abstracts, November 15, 1996.

(1) Host-Guest Complexation 67.

(2) We warmly thank the U. S. Public Health Service for supporting

grant GM-12640, and Dr. Kurt Loening for assistance with nomen-

clature.

(3) Cram, D. J .; Cram, J . M. Container Molecules and Their Guests.

In Monographs in Supramolecular Chemistry; Stoddart, J . F., Ed.;

Royal Society of Chemistry: Thomas Graham House, Science Park,

Cambridge, U.K., 1994; pp 131-216.

(4) Kurdistani, S. K.; Helgeson, R. C.; Cram, D. J . J . Am. Chem.

Soc. 1995, 117, 1659-1660.

(5) NMP stands for N-methylpyrrolidinone; DMA for (CH₃)₂-

NCOCH₃. GB/SA is the Generalized Born radii (GB)/solvent-accessible

surface area (SA), an empirical solvation model. It is a semianalytical

treatment of solvation and provides a volume-based continuum model

for the electrostatic (polarization) component.¹³

9324 J . Org. Chem., Vol. 61, No. 26, 1996

Yoon et al.

for 2400 h, 7.naphthalene was formed in 40% yield. In

all the experiments of Chart 2, the cooled reaction

mixtures were flooded with methanol which precipitated

the complexes, most of which were purified by thick layer

chromatography with CHCl₃as the mobile phase. Com-

plexes 9.1,4-(MeO)₂C₆H₄, 10.4-MeC₆H₄OMe, 10.1,4-

(MeO)₂C₆H₄, and 11.4-MeC₆H₄OMe were used without

chromatographic purification. With the exception of

7.naphthalene, in which equilibrium was probably not

established, the yields varied from 80-92%.

Isola ted P r od u cts Cor r ela te w ith P or ta l Size.

Comparisons of CPK models suggest the inner volumes

of these hosts differ very little from one another, but that

the two portals that flank the last bridge introduced

increase in size and conformational adaptivity in passing

from 7 to 8, and from 7 to 10 or 11. The portals flanked

by two (CH₂)₄groups already present in 2 are not greatly

affected by the length of the fourth bridge. These two

portals are invariant and composed of 26-membered

rings, as compared to the other two portals that flank

the fourth bridge. The latter vary in ring size with

changes in the fourth bridge as follows: 4, 23-membered

rings; 5, 24-membered rings; 6, 25-membered rings; 7,

26-membered rings; 8, 27-membered rings; 9, 26-mem-

bered rings with four bridging atoms coplanar; 10, 27-

membered rings with five of the bridging atoms coplanar;

and 11, 27-membered rings with five of the bridging

atoms coplanar. To enter or exit the inner phase of these

hosts, potential guests must pass through these rings,

and for the guests studied, the larger portals are going

to be the most used. With 4-7 and 9, these are likely to

be the original 26-membered portals; with 8, 10, and 11,

the larger portals are probably used.

OMs in NMP probably initially produced 8.NMP, whose

NMP was replaced with CHCl₃to give 8.CHCl₃(stable

to manipulation) during chromatographic purification

with CHCl₃as the mobile phase; 2,3-bis(bromomethyl)-

quinoxaline provided 9.NMP, 9.DMSO, and 9.1,4-

(MeO)₂C₆H₄(HMPA as solvent containing a 100:1 molar

ratio of guest 1,4-(MeO)₂C₆H₄to 2). This last reaction,

carried out at 24-50 °C, exemplifies the “sealing in” of a

relatively large guest during introduction of the fourth

bridge. With m-xylyl dichloride in NMP, whatever

10.NMP was produced initially went to 10.CHCl₃

during isolation. Similarly, 2,6-bis(chloromethyl)pyridine

ultimately gave 11.CHCl₃although the shell closure was

conducted in NMP. The temperatures for the shell

closures varied from 24-75 °C, and the times from 48-

53 h.

Chart 2 indicates the starting materials and products

for the thermally induced formations of new hemicarce-

plexes by either guest exchanges, or from empty host plus

guests. Where possible, the new guest served as solvent

for the starting empty host or complex. When necessary

for solubility reasons Ph₂O or HMPA were used as

solvents whose molecular volumes are too large to occupy

the inner phases of any of these hosts. In such cases,

guest-to-host molar ratios of at least 100 were employed.

Temperatures and times for these equilibrations with one

exception ranged respectively from 140-165 °C, with

times of 72-96 h. The exception was when 7 and

naphthalene dissolved in Ph₂O were heated at 200 °C

Seven New Hemicarcerands

J . Org. Chem., Vol. 61, No. 26, 1996 9325

Ch a r t 1. F ou r th Br id ge Don or s Rea ct w ith Diol 2 To Give Eith er Host.Gu est Com p lexes or Hosts Wh en

Hea ted in th e P r esen ce of Cs₂CO₃

This analysis grossly correlates with observations

incidental to the syntheses of the hosts. Thus the

originally formed “sealed in” complexes of Chart 1 involv-

ing 4-7 and 9 survived their isolation in the presence of

CHCl₃during chromatography. Even empty 7 survived

isolation without complexing CHCl₃.⁴However, 8, 10,

and 11 lost their putative original guest (NMP) during

isolation in favor of complexing CHCl₃. Models show

little constrictive hindrance to the departure of NMP and

entrance of CHCl₃to the interior of these hosts. On the

other hand, the slow complexation of naphthalene by

empty 7 (2400 h to produce 40% complex at 200 °C)

correlates with the fact that in CPK models complexation

requires considerable modification of stable conforma-

tions and some bond angle adjustments in many parts

of the host.

The numbers of non-hydrogen atoms in the guests

introduced into hosts in this study ranges between 4

(CHCl₃, (CH₃)₂SO) and 12 (1,2,3-(MeO)₃C₆H₃), the most

common guests containing 8 to 10 non-hydrogen atoms,

six often in the form of a benzene ring. Host 7 in other

studies was found to incarcerate 33 other guests of widely

differing structures possessing most of the common

functional groups, none of which contained more than

10 non-hydrogen atoms.^6,7Those selected for the current

study were chosen generally for their size, solubility

properties, boiling points, simplicity of their ¹H NMR

spectra, and probability of forming a hemicarceplex.

Almost all organic compounds containing 8 or less non-

hydrogen atoms are good candidate guests for the hosts

of this study. However, it is highly probable that hosts

8, 10, and 11 are capable of incarcerating larger guests

than 4-7 and 9, although the only example reported here

is 10.1,2,3-(MeO)₃C₆H₃.

Cr yst a l St r u ct u r es of 8.4-MeC₆H ₄OMe a n d

10.CHCl₃. Crystal structures of 8.4-MeC₆H₄OMe∪

3

2PhNO₂(R ) 0.162) and 10.CHCl₃∪2PhNO₂‚2Ph-

3

NO₂(R ) 0.17) were determined.⁸Chart 3 provides both

side and partial top stereoviews of the complexes. In the

latter, the two sets of four oxygens that terminate the

intermolecular bridges are connected by heavy lines to

form two near planar squares attached to one another

by the four interhemispheric bridges, the rest of the host

being omitted. These top view partial structures both

demonstrate that the carbons and hydrogens of the four

bridges all lie outside the volume of a solid figure defined

by the eight oxygens at its corners. This geometry

reflects the fact that the unshared electron pairs of all

eight oxygens face inward toward the cavity, and their

bonds to the bridges must diverge from the cavity. This

arrangement gives an out-in-out orientation of unshared

electron pairs for the three oxygens attached to adjacent

carbons on each of the eight benzene rings of the host,

which provides for the greatest compensation of dipoles

and lowest energy.

Crystalline 8.4-MeC₆H₄OMe∪2PhNO₂is isostruc-

3

tural with more than 25 hemicarceplexes of 7.guest∪

3

(8) The authors have deposited atomic coordinates for these struc-

tures with the Cambridge Crystallographic Data Center. The coordi-

nates can be obtained, on request, from the Director, Cambridge

Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ,

UK.

(6) Robbins, T. A.; Knobler, C. B.; Bellew, D. R.; Cram, D. J . J . Am.

Chem. Soc. 1994, 116, 111-122.

(7) Robbins, T. A.; Cram, D. J . J . Am. Chem. Soc. 1993, 115, 12199-

12200.

9326 J . Org. Chem., Vol. 61, No. 26, 1996

Yoon et al.

Ch a r t 2. New Hem ica r cep lexes P r ep a r ed by Ma ss-La w Dr iven Gu est Exch a n ge or fr om F r ee

Host-Com p lexin g Solven t or Solu tes, Both Meth od s a t Eleva ted Tem p er a tu r e

2PhNO₂containing four [O(CH₂)₄O] bridges, and there-

fore the parameters for the two cavitand moieties and

for the two PhNO₂molecules could be used to locate the

guest, the three O(CH₂)₄O bridges, and the O(CH₂)₅O

bridge. Because the complex is crystallographically

centrosymmetric, the guest is required to be disordered.

A “pair” of bridges is also required to have disorder (the

unlike bridges related by the center of symmetry). The

4-MeC₆H₄OMe guest molecule in the host cavity is

disordered because it lies on the crystallographic center

of symmetry and is further disordered because it lies on

either diagonal of the rectangular solid described by the

eight terminal oxygens of the bridges as seen in the top

partial stereoview. The four bridge-terminating oxygens

attached to each bowl are coplanar within 0.01 (2) Å, and

the planes are 4.10 Å distant from one another. These

two planes are not rotated around the polar axis with

respect to one another (see top view). The two PhNO₂

molecules are associated with the CH₂CH₂Ph “feet”

attached to the northern and southern hemispheres, with

the nitro groups turned toward the globe of the host (see

Chart 3, side view).

In the crystal structure of 10.CHCl₃∪2PhNO₂‚

3

2PhNO₂, the complex lies on a two-fold axis. The CHCl₃

is located in the cavity, but is disordered. Each set of

four CH₂CH₂Ph groups surrounds a PhNO₂molecule,

with the nitro group turned toward the globe. The other

two PhNO₂molecules are interstitial. The PhNO₂mol-

ecules are omitted from the drawings of Chart 3. The

two sets of four oxygens that terminate the four inter-

hemispheric bridges form two planes (( 0.02 (2) Å). The

two planes miss being parallel to each other by 5.7°. The

oxygen atoms of each interhemispheric bridge are distant

from one another by the values (Å): OCH₂C₆H₄CH₂O,

4.47 (2); O(CH₂)₄O (flanking bridges), 4.02 (2) and 4.06

(2); O(CH₂)₄O (opposite bridge), 3.57 (2). The average

distance between the two oxygen planes is 4.03 Å, less

than the 4.10 Å distance in 8.4-MeC₆H₄OMe. The

carbons and hydrogens of these four bridges all lie outside

the solid defined by the eight apical oxygens. The two

Seven New Hemicarcerands

J . Org. Chem., Vol. 61, No. 26, 1996 9327

Ch a r t 3. Ster eoview s of Cr ysta l Str u ctu r es of Hem ica r cep lexes

oxygen planes are slightly rotated and displaced from

their best central axis with respect to one another. The

top view of 10 shows that the two portals flanking the

OCH₂C₆H₄CH₂O bridge are slightly more open than the

two portals flanking the O(CH₂)₅O bridge in 8. The long

bridges are clearly visible at about 1 o’clock and 5 o’clock

in the top views of 8 and 10, respectively.

It also seems likely that ∆δ values should measure how

far the Me protons are thrust into the shielding faces of

the four aryls. Table 1 indicates the ∆δ values for the

five N-Me protons decrease in the following order with

increases in the effective lengths of the unique bridge of

the host as follows: CH₂CdCCH₂(9), 3.87 ppm; CH₂(4),

3.83; CH₂CH₂(5), 3.63; CH₂CH₂CH₂(6), 3.60; CH₂CH₂-

CH₂CH₂(7), 3.59 ppm. By effective lengths, we mean

the effect on the long axis of the inner phase of the hosts.

Interestingly, the coplanarity requirement of the four-

atom 2,3-dimethylenequinoxaline bridge of 9 forces it in

CPK models to rotate about its C₂axis and thus act as a

bridge even slightly shorter than the CH₂bridge of 4.

The effective lengths of the other four bridges fall in the

expected order, with little difference between the (CH₂)₃

and (CH₂)₄bridges. The H^bprotons provide a similar

sequence: CH₂CdCCH₂, 3.19; CH₂, 3.13; CH₂CH₂, 2.95;

CH₂CH₂CH₂, 2.83; CH₂CH₂CH₂CH₂, 2.82 ppm. The H^c

protons give a somewhat different order: CH₂, 3.15;

CH₂CdCCH₂, 3.05; CH₂CH₂, 2.79; (CH₂)₃, 2.72; and

(CH₂)₄, 2.68 ppm. The only distinguishable H^dprotons

were when the host bridges were CH₂CdCCH₂and CH₂,

which gave the same ∆δ values (1.46 ppm). As expected,

for each complex, the three or four different protons

available provided decreases in ∆δ values in the order

H^a> H^b≈ H^c> H^d. In models, the H^cand H^dprotons

cannot penetrate as deeply into the polar regions of the

hosts as can the H^aprotons of the Me group.

Cor r ela t ion s b et w een Gu est St r u ct u r es a n d

Ch a n ges in Ch em ica l Sh ifts of In ca r cer a ted a n d

1

F r ee Host P r oton s in H NMR Sp ectr a . Table 1 lists

δ for 12 guests dissolved in CDCl₃, 43 hemicarceplexes

of these guests dissolved in CDCl₃, and ∆δ values for the

guest protons (∆δ ) δ_free- δ_complexed). In all cases except

for the OH protons in 7.2-MeC₆H₄OH and 8.2-Me-

C₆H₄OH the δ values moved upfield upon incarceration,

due to the shielding effects of the faces of the eight aryl

groups that line much of the surface of the inner phase.

The ∆δ values range from a low of -0.76 (in 8.2-Me-

C₆H₄OH) to a high of 4.41 ppm (in 7.1,3-(MeO)₂C₆H₄).

Model examinations of 4.NMP, 5.NMP, 6.NMP,

7.NMP, and 9.NMP indicate that the Me of the guest

must occupy one of the polar, bowl-shaped interiors of

the four hosts, and thus anchor the guest in the four

hosts. The other protons of the CH₂CH₂CH₂parts of the

guest are arranged in an arc which stretches like the

handle of a tea kettle through the equator and past the

other hemisphere of the inner phase to attach to the CdO

(the spout of the tea kettle) whose axis points roughly

toward the lower parts of the bridging groups of the hosts.

Thus the ∆δ values of the four kinds of protons provide

a sort of map of the shielding character of the different

parts of the inner surfaces of the closely related hosts.

The ∆δ values for Me₂SO (singlets) are smaller than

those for H^aof NMP and vary much less with changes in

the host’s unique bridges, probably because this guest is

smaller than NMP and less closely held. The order of

∆δ with changes in the unique bridges is as follows:

CH₂CdCCH₂, 3.17; CH₂, 3.14; (CH₂)₃, 2.97; (CH₂)₄, 2.95;

CH₂CH₂, 2.94 ppm. Again, the effective lengths are the

1

The guest is presumed to rotate rapidly on the H NMR

time scale around the axis of the N-Me bond, which is

roughly coincident with the long polar axis of the host.

9328 J . Org. Chem., Vol. 61, No. 26, 1996

Ta ble 1. Effect of Host Str u ctu r e on 500 MHz ¹H NMR Sp ectr a of Gu ests in CDCl₃a t 25 °C

Yoon et al.

shortest for the CH₂CdCCH₂and CH₂bridges, but the

other three ∆δ values do not vary significantly with the

numbers of methylenes.

As observed for the carceplex of MeCONMe₂(DMA)

whose host was identical to 4 except all four bridges were

CH₂, the H^aand H^bmethyls of DMA incarcerated in 4-7

give substantially higher ∆δ values (range 4.00-3.44

ppm) than the H^cmethyls (range, 1.36-1.30 ppm). The

H^aand H^bmethyls lie on the long axis of DMA, which

must be close to being coincident with the long axes of

Seven New Hemicarcerands

J . Org. Chem., Vol. 61, No. 26, 1996 9329

the host cavities. Thus the H^aand H^bmethyls are located

in the two polar (most shielding) parts of the host’s

interior, and the H^cmethyls lie in the equatorial region

of the bridges. The H^aprotons’ ∆δ value is 4.00 with the

shortest unique bridge (CH₂), but decreases to 3.75, 3.76,

and 3.72 ppm, respectively, as that bridge becomes CH₂-

CH₂, (CH₂)₃, and (CH₂)₄. The H^bprotons’ ∆δ values

decrease more markedly and regularly with the length-

ening of the unique bridge as follows: CH₂, 3.92; CH₂-

CH₂, 3.58; (CH₂)₃, 3.55; (CH₂)₄, 3.44 ppm. The equato-

rially-located H^cprotons provide ∆δ values that vary little

and irregularly with bridge length.

faces, and their ∆δ values show the greatest range, 1.51

to 1.72 ppm. It is more difficult in models of complexes

of 1,2-(MeO)₂C₆H₄to locate the contacting parts since

each OMe group inhibits its neighboring OMe group from

penetrating the polar parts of the cavity. In none of the

¹H NMR spectra of the four complexes that were taken

could the δ values for the H^amethyl protons be deter-

mined because of the overlap of host and guest signals.

Probably a family of structures, nonequilibrating on the

NMR time scale and close in energy, is responsible for

the uninformative spectra.

Like 1,4-(MeO)₂C₆H₄as guest, 4-MeOC₆H₄Me is highly

complementary in shape to the inner phases of these

larger hosts in molecular models. The ∆δ values for the

four different kinds of protons in 4-MeOC₆H₄Me in its

four complexes are very close to one another: for H^a, with

(CH₂)₄as a fourth bridge, 4.13; (CH₂)₅, 4.06; 1,3-

(CH₂)₂C₆H₄, 4.04; 2,6-(CH₂)₂pyridine, 4.07 ppm. The

respective ∆δ values for H^b, H^c, and H^din the four

complexes are the following: 0.94, 0.97, 0.94, and 1.03;

1.22, 1.14, 1.08, and 1.19; 4.40, 4.27, 4.25, and 4.27 ppm.

Both model examination and ∆δ values for the H^b

methyl protons of 2-HOC₆H₄Me indicate the Me group

occupies one of the polar regions of the host in the two

complexes prepared and examined. The ∆δ values are

as follows: unique bridge (CH₂)₄, 4.06; (CH₂)₅, 3.99 ppm.

The phenolic hydroxyl protons (H^a) are actually deshield-

ed, with ∆δ values of -0.46 and -0.76, respectively.

These acidic protons probably hydrogen bond the oxygens

that terminate the bridges at that end of the host in each

complex whose hemispheres are occupied by the Me

groups. As expected, the H^earyl protons para to the

anchoring Me groups of the guests provide high ∆δ values

of 4.09 for the (CH₂)₄bridged and 3.92 for the (CH₂)₅

bridged complexes, respectively. The remaining aryl

protons with observable δ, H^dand H^f, in the two

complexes have ∆δ values between 0.78 and 1.45 ppm.

The most crowded complex prepared is 10.1,2,3-

(MeO)₃C₆H₃, whose unique bridge is 1,3-(CH₂)₂C₆H₄.

Models of this complex resemble those of 10.1,3-

(MeO)₂C₆H₄. The aryl plane of this guest is tilted with

respect to the equatorial plane of the host, with one H^a

methyl protruding into one polar region of the host, and

the second H^amethyl protruding into the other polar

region. In models of 10.1,2,3-(MeO)₃C₆H₃, the middle

MeO group is close to being coplanar with its attached

aryl group, which places the H^bmethyl protons in the

low-shielding equatorial region. The ∆δ values are

consistent with such a structure, being 4.26 for H^aand

0.81 for H^bin 10.1,2,3-(MeO)₃C₆H₃, the former being

comparable to 4.33 ppm for H^ain 10.1,3-(MeO)₂C₆H₄.

In models, 1,4-Me₂C₆H₄fits comfortably in 4-7 with

each of the two methyl groups occupying one of the two

hemispheric bowls with the long axes of host and guest

being essentially coincident. The H^aprotons of these

methyls exhibit ∆δ values that change relatively little

with the unique bridge changes as follows: CH₂, 4.34;

CH₂CH₂, 4.25; (CH₂)₃, 4.33; (CH₂)₄, 4.40 ppm. The non-

monatonic orders in some of these patterns probably

reflect different degrees of rotation of the two hemi-

spheres with respect to one another as the unique bridge

lengths change, and the host adapts to the steric require-

ments of these relatively rigid guests. The hosts more

than the guests have bond angle and conformational

degrees of freedom that can vary cumulatively to mini-

mize the energies of the complexes of 4-7 and 9. The

enlargement of the host’s portal should be more temper-

ature-sensitive than the compressibility of the guest.

Both host inner phases and guest volumes are larger

for the complexes whose ∆δ values are reported in the

bottom two-thirds of Table 1. The two protons (H^a) of

CHCl₂CHCl₂in models occupy niches defined by the

much larger Cl atoms, and therefore cannot reach the

inner shielding surfaces of the host when incarcerated.

Accordingly, the ∆δ values for 7, 8, and 10 with unique

bridges (CH₂)₄, (CH₂)₅, and 1,3-(CH₂)₂C₆H₄are 1.20, 1.66,

and 1.60 ppm. In contrast, with naphthalene as guest,

the protons are exposed, and in models of their com-

plexes, the H^bprotons rest against the high-shielding

faces of the northern and southern hemispheres of the

host. Accordingly, the ∆δ values for H^bare high and are

as follows (unique bridges identify the host): (CH₂)₄, 4.21;

(CH₂)₅, 3.94; 1,3-(CH₂)₂C₆H₄, 3.95; 2,6-(CH₂)₂pyridine,

3.93 ppm. As expected, the shortest unique bridge,

(CH₂)₄, provides the highest ∆δ value.

The next three guests of Table 1 are the three isomeric

dimethoxybenzenes. The most complementary relation-

ship between host and guest with regard to the partners

sharing the largest surface area is found in the complexes

of 7, 8, 9, and 10 with 1,4-(MeO)₂C₆H₄. The H^amethyl

protons in models of the complexes are thrust nonsym-

metrically into each of the two hemispheres of the hosts.

Their ∆δ values are as follows: unique bridge (CH₂)₄,

4.23; (CH₂)₅, 4.18; CH₂CdCCH₂, 4.22; and 1,3-(CH₂)₂C₆H₄,

4.15 ppm. The inner phases of these complexes appear

to be very similar to one another in shape. More

surprisingly, the same thing is observed for the 1,3-

(MeO)₂C₆H₄isomer. In models, the two methyls nicely

fit into the two hemispheres of the host, which is

consistent with the high ∆δ values for the H^aprotons of

the two methyls, as follows: (CH₂)₄, 4.41; (CH₂)₅, 4.35;

1,3-(CH₂)₂C₆H₄, 4.33; and 2,6-(CH₂)₂pyridine, 4.30 ppm.

In models, the H^bproton is located in the equatorial

region of the four complexes, and their ∆δ values range

from 1.08 to 1.01 ppm. The H^cprotons’ ∆δ values are

somewhat higher, since they contact the edge of the aryl

Important conclusions emerge from these correlations

between models of host-guest complexes, and the ∆δ

shielding-deshielding patterns of incarcerated guests. (1)

When only a single CPK model of a complex can be

assembled in which the various parts of each complexing

partner are pretty well fixed with respect to one another,

the correlation between structural conclusions based on

¹H NMR ∆δ values and the model structure is high.

Examples involve complexes of DMA, 1,4-(Me)₂C₆H₄, 1,4-

(MeO)₂C₆H₄, 1,2,3-(MeO)₃C₆H₃, and 4-MeOC₆H₄Me. (2)

When several models of a given host complex can be

1

assembled, the H NMR spectral peaks become broader,

and the structural information contained in ∆δ values

becomes more restricted and ambiguous. Examples are

complexes of 1,2-(MeO)₂C₆H₄and Me₂SO.

9330 J . Org. Chem., Vol. 61, No. 26, 1996

Yoon et al.

Rep r esen ta tive Exa m p les of Effects on Host NMR

Sp ectr a a s Len gth s a n d Ch a r a cter of On e Br id ge

of 7 a n d Its Gu ests a r e Ch a n ged . Figure 1 records

the interesting parts of the 500 MHz ¹H NMR spectra in

CDCl₃at 25 °C of the host parts of complexes involving

4-6 and 9. Replacement of one O(CH₂)₄O bridge in 7 by

one O-A-O bridge in 4-6 and 9 destroys the formal C₄

axis of 7, but leaves a formal mirror plane defined by

the two oxygens that terminate the unique bridge, and

the two oxygens that terminate the most remote O(CH₂)₄O

bridge. This leads in principle to three different kinds

of interhemispheric OCH₂protons, four different kinds

of intrahemispheric OCH₂protons, and two different

methine C₃CH protons.

Some of these closely related protons provide resolved

signals in the spectra of Figure 1. For example, in the

spectrum of 4.NMP, the three different H^esignals for

e

OCH₂CH₂CH₂CH₂O are close together, whereas in

4.1,4-(Me)₂C₆H₄, they are widely separated, probably

because of their varying locations with respect to the

shielding magnetic fields of their tightly-held aryl guest.

In contrast, two sets of H^band H^dsignals are visible in

the 4.NMP spectrum but only one set (H^band H^d) in

that of 4.1,4-(Me)₂C₆H₄. In the spectrum of 5.NMP, two

H^e, two H^d, but only one H^bsignals are visible. In the

spectrum of 6.NMP, one H^e, one H^b, and two H^dpeaks

are apparent. In all of these four spectra only one

methine signal is observed, but in those of 9.NMP and

9.1,4-(MeO)₂C₆H₄, two are clearly discernible. The

spectrum of 9.NMP contains a single H^b, two H^dsignals,

but only one H^epeak. In contrast, that of 9.1,4-

(MeO)₂C₆H₄provides all three H^e, two H^b, and two H^d

signals. These examples as well as many others found

in the Experimental Section show how extensively the

¹H NMR spectra of the host protons vary with guest

character.

F or ce F ield Ca lcu la tion s of Str u ctu r a l Mod els for

4.NMP -7.NMP Com p lexes. The conformations of

hosts and complexes were explored with force field

calculations using AMBER* in the program MACRO-

MODEL.⁹This force field has proven useful for the

investigation of hemicarceplex conformations and the

dynamic processes involved in complexation and decom-

plexation.^10-12For computational simplification, the

eight CH₂CH₂C₆H₅groups of 4-7 were replaced with CH₃

groups to provide 4-Me, 5-Me, 6-Me, and 7-Me, respec-

tively. Conformations of the four interhemispheric bridges

of 4-Me to 7-Me were explored with a Monte Carlo (MC)

search by varying the torsional angles. Host 7-Me was

constructed by the graphical input module in MACRO-

MODEL. The starting geometries for 6-Me, 5-Me, and

4-Me were obtained by removing one, two, and three

methylenes, respectively, from one of the interhemi-

spheric bridges of 7-Me, and then optimizing the result-

ing structures with the AMBER* force field. The total

number of MC steps used for each structure was 500,

and each MC step began with the geometry of the least-

used structure of the previous MC steps. Many low-

energy conformers of 7-Me were located. The conforma-

tion of 7-Me derived from the crystal structure of 7.1,4-

(9) Mohamadi, F.; Richards, N. G. J .; Guida, W. C.; Liskamp, R.;

Caufield, C.; Chang, G.; Hendrikson, T.; Still, W. C. J . Comput. Chem.

1990, 11, 440.

F igu r e 1. Partial 500 MHz ¹H NMR spectra of hosts of

4.Guest, 5.Guest, 6.Guest, and 9.Guest.

(10) Sheu, C.; Houk, K. N. J . Am. Chem. Soc. 1996, 118, 8056-

8070.

(11) Nakamura, K.; Houk, K. N. J . Am. Chem. Soc. 1995, 117, 1853-

1854.

Me₂C₆H₄⁶is very close structurally to the global minimum

obtained by the MC search, and its energy is only 0.6

(12) Houk, K. N.; Nakamura, K.; Sheu, C.; Keating, A. E. Science

1996, 273, 627-629.

Seven New Hemicarcerands

J . Org. Chem., Vol. 61, No. 26, 1996 9331

Analysis of the calculated structures of 4-Me to 7-Me

provides the average distance between two planes, each

defined by the four aryl carbons at the termini of the four

interhemispheric bridges in the respective northern and

southern hemispheres. Table 2 lists the results. These

distances (Å) increase monotonically with increasing

lengths of the unique bridges in the hosts and range from

5.1 to 6.0 Å. Two other parameters locate the center of

the guest NMP methyl group with respect to the center

of the four proximate benzenes of the host: the distance

(d) between these two centers: the average deviation

from 90° of the angle θ between vector d and one

connecting the center of the benzene with the terminus

of the interhemispheric bridge. These parameters are

visualized in diagram 1.

F igu r e 2. Superposition of 10 low-energy conformers of 7-Me.

These distances and θ angle deviations are listed in

Table 2, and they correlate, respectively, with the number

of methylenes in the unique bridges as follows: CH₂, 3.5

Å and 9.8°; (CH₂)₂, 3.8 Å and 4.9°; (CH₂)₃, 4.0 Å and 4.5°;

(CH₂)₄, 3.9 Å and 4.4°. These parameters also correlate

with the upfield chemical shift changes in the H NMR

spectral ∆δ values for the methyl group of NMP upon

incarceration in 4-7, listed in Table 2.

kcal mol^-1higher by AMBER*. The northern and

southern bowls of the hemicarcerand are very rigid and

the flexibility of the molecule is mainly due to the

interhemispheric bridges. Figure 2 is the superposition

of 10 low-energy conformers, all of which are within 1.5

kcal mol^-1of the global minimum.

Starting geometries for the NMP complexes were

obtained manually by docking the NMP guest inside the

cavity of the hemicarcerand in various orientations.

These were energy-minimized with the AMBER* force

field. The lowest-energy conformer of each carceplex was

then used as the starting geometry in an optimization

utilizing the simulated annealing method. The cooling

process was linear and continuous from 500 K to 50 K

over a 1000 ps molecular dynamics simulation. The

structure of the lowest-energy conformer for each complex

is found in Figure 3.

1

Ap p r oxim a te Ha lf-Lives for Decom p lexa tion of

Com p lexes In volvin g La r gest Hosts a n d Gu ests.

Much qualitative information dealing with complexes

stable or unstable to isolation conditions is found in Chart

1. Isolation involved evaporation of aprotic dipolar

solvents under vacuum under 45 °C, flooding the reaction

mixtures with methanol, and subjecting the methanol-

washed precipitate to thick layer chromatography with

CHCl₃as the mobile phase. Complexes of 4, 5, 6, 7,⁶and

9 with NMP, DMSO, and DMA as guests are stable to

these manipulations, whereas free 6 and 7 did not

complex under similar conditions (Chart 1). In contrast,

8.NMP, 10.NMP, and 11.NMP went to 8.CHCl₃,

10.CHCl₃and 11.CHCl₃under the same conditions.

Complexation of 4-7 or 9 and decomplexation of their

complexes involves guests passing through 23- to 26-

membered rings. Only guests as small as CH₂Cl₂or

pentane (but not CHCl₃) readily entered and departed

the interior of 7 in solution at 25 °C.⁶However, CHCl₃

readily passed through the 27-membered ring portals of

8, 10, and 11. Temperatures of 100-200 °C appear

needed for hosts with 26-membered and 27-membered

ring portals to complex or decomplex guests containing

6-12 atoms other than hydrogen (Chart 2 and prior

work^3,6).

The best plane of the guest in the calculated structures

of Figure 3 is roughly placed in the plane of the page,

with the N-methyl pointing upward into the north polar

cap. In all four structures, the best plane of the guest

and page roughly bisects two of the portals, with two of

the bridges flanking the CdO group, and two bridges

flanking the two H’s of the NCH₂group. The four

CH₂CH₂CH₂N hydrogens of the guest point generally

toward the southern polar part of the host, which is

1

consistent with the substantial upfield shifts in their H

NMR spectra.

A general and important feature of these calculated

structures is that the electron pairs of the oxygen termini

of the interhemispheric bridges all face inward, opposite

to the directions in which the intrahemispheric spanner

oxygens face, thus minimizing the energy of their dipole-

dipole interactions. Consequently, the carbon chains of

the interhemispheric bridges lie outside of the distorted

cube defined by the eight oxygens to which these chains

are attached. In these respects the calculated structure

of host 7 in 7-Me.NMP resembles the crystal structures

of 7.Gu ests, many of which have been determined,⁶and

also the structures of 8.4-MeC₆H₄OMe and 10.CHCl₃

reported here (Chart 3).

Because little was known about the kinetic stability

of complexes of hosts with 27-membered ring portals, we

determined the approximate half-lives for decomplexation

in CDCl₃at 25 °C of the complexes between 7, 8, 10 and

4-MeC₆H₄OMe, 4-MeOC₆H₄OMe, and 3-MeOC₆H₄OMe.

Table 3 records the t_1/2values for those decomplexations

that could be detected.

Complexes of 7 with all three guests gave no ¹H NMR-

detectable uncomplexed guest after 336-720 h. Half-

9332 J . Org. Chem., Vol. 61, No. 26, 1996

Yoon et al.

F igu r e 3. Force field calculated structures derived for molecules of 4.NMP , 5.NMP , 6.NMP , and 7.NMP , simplified by

substitution of CH₃for CH₂CH₂C₆H₅groups in the hosts to give, respectively, 4-Me.NMP , 5-Me.NMP , 6-Me.NMP , and

7-Me.NMP . In the drawings, H atoms are omitted from the hosts and the unique bridges are on the right, toward the viewer.

Ta ble 2. Resu lts of F or ce F ield Ca lcu la tion s of Str u ctu r es of NMP Com p lexes of Hosts 4-Me-7-Me^a

average distances between centers (Å)

complex

modeled

unique

bridge

interhemispheric

bridge termini^b

NMP methyl to

aryl faces^c

average deviation

observed ¹H NMR ∆δ for

guest CH₃(ppm)^d

of Θ from 90 ° ^c

4-Me.NMP

5-Me.NMP

6-Me.NMP

7-Me.NMP

OCH₂O

5.1

5.7

5.9

6.0

3.5

3.8

4.0

3.9

9.8

4.9

4.5

4.4

3.83

3.63

3.60

3.59

O(CH₂)₂O

O(CH₂)₃O

O(CH₂)₄O

a

b

The eight CH₂CH₂C₆H₅feet of hosts 4-7 have been replaced by CH₃feet to simplify the calculations. Hemispheric planes defined

by aryl carbon termini of bridges. ^cSee Diagram 1. H^aprotons’ ∆δ values, Table 1.

d

life values for decomplexations of 8.4-MeC₆H₄OMe, 8.3-

MeOC₆H₄OMe, and 8.4-MeOC₆H₄OMe are as follows:

>720 h, >600 h, and 310 h. Half-life values for decom-

plexations of 10.3-MeOC₆H₄OMe, 10.4-MeC₆H₄OMe,

and 10.4-MeOC₆H₄OMe decreased respectively as fol-

lows: 250 h, 85 h, and 8 h.

These results emphasize how large a difference one

methylene can make in a portal’s ability to allow or

Seven New Hemicarcerands

J . Org. Chem., Vol. 61, No. 26, 1996 9333

Ta ble 3. Decom p lexa tion Ha lf-Lives in Hou r s in CDCl₃

Ta ble 4. F or ce F ield AMBER* Ca lcu la tion s of Bin d in g

En er gies a n d Activa tion En er gies for Decom p lexa tion of

7-Me.NMP , 8-Me.NMP , a n d 10-Me.NMP , a n d th e

Dissection of th e Activa tion En er gies for

Decom p lexa tion in to In tr in sic a n d Con str ictive

Com p on en ts

a t 25 °C

complex

energies

phase (kcal mol^-1

gas ∆E

CHCl₃∆E

)

7-Me.NMP 8-Me.NMP 10-Me.NMP

-19.3

-11.5

39.0

-19.8

-13.4

27.1

-18.3

-12.2

21.3

q

gas

∆E

(decomplex)

19.3

19.8

18.3

(intrinsic)

19.7

7.3

3.0

(constrictive)

one of the larger portals. The reaction coordinate con-

nects Du with the center of the methyl of incarcerated

NMP. By gradually decreasing the distance between the

guest molecule and the defined dummy atom, the activa-

tion energy for the guest escape process was estimated

by energy minimization for each step. For the host

molecules with all their intrahemispheric bridges (span-

ners) in their favored chair conformations, the activation

energy barriers for the decomplexation of NMP from

model hosts 7-Me, 8-Me, and 10-Me were calculated.

Figure 5 is a plot of energy versus distance for the three

disallow passage of a guest from the inner to the bulk

phase of a host at 25 °C. Thus 7.guest⁶and 12.guest¹⁴

complexes containing 26-membered ring portals are

stable indefinitely at 25 °C in solvent (such as CDCl₂-

CDCl₂) with guests as small as CH₃CH₂I, CH₃COCH₃,

(CH₂)₄O, and CH₃CO₂CH₂CH₃,^3,6as well as larger guests

such as 4-MeC₆H₄OMe, 3-MeOC₆H₄OMe, and 4-MeOC₆H₄-

OMe in CDCl₃. Host 8.guest with two 27-membered

ring portals has decomplexation half-lives in the hun-

dreds of hours, and 10.guest with two 27-membered ring

portals with a m-xylyl group substituted for a (CH₂)₃

moiety in the middle of the unique bridge has half lives

that range from 250 to 8 h for the three disubstituted

benzene guests. Thus the m-xylyl group offers somewhat

less resistance to guest passage than the (CH₂)₃group,

probably because of the latter’s six hydrogens.

F or ce F ield Ca lcu la tion s of Bin d in g En er gies a n d

Act iva t ion E n er gies for Decom p lexa t ion of

7-Me.NMP , 8-Me.NMP , a n d 10-Me.NMP . To obtain

further insight regarding the differences in stabilities of

complexes 7.NMP, 8.NMP, and 10.NMP, binding

energies in the gas phase and in chloroform were

calculated using the AMBER* force field program men-

tioned previously. As before, the calculations were

simplified by replacing the eight CH₂CH₂C₆H₅groups of

each host with eight CH₃groups to give, respectively,

7-Me.NMP, 8-Me.NMP, and 10-Me.NMP. The bind-

ing energies are defined by the expression

q

complexes from which the ∆E _(decomplex)values were taken.

The absolute values listed (Table 4) of 39.0, 27.1, and

21.3 kcal mol^-1are probably somewhat high, but their

relative values are meaningful. Particularly interesting

is the dissection of these activation energies into intrinsic

and constrictive components, using the equation,

q

∆E _{(constrictive)}) ∆E _(decomplex)- (-∆E) )

q

14

(complexation)

∆E

Table 4 lists the ∆E^q

values, which are as

(constrictive)

follows: for 7-Me.NMP, 19.7; for 8-Me.NMP, 7.3; for

10-Me.NMP, 3.0 kcal mol^-1. The percent contribution

made by constrictive binding to the total activation

energy for the three respective decomplexations is 51%,

27%, and 14%.

The thermodynamic ∆E values found in Table 4

correlate well with expectations based on molecular

model examinations.

The ∆E values for the calculated binding energies for

7-Me.NMP, 8-Me.NMP, and 10-Me.NMP in the gas

phase provide an average of 19.1 ( 0.8 kcal mol^-1, and

in CHCl₃, an average of 12.4 ( 1.0 kcal mol^-1

. The

maximum spread in each set of three values is only 2

kcal mol^-1, which correlates with the facts that the NMP

guest is common to the three complexes, the three hosts

differ only in one of their bridges, and these unique

bridges differ mainly in their lengths and in the small

differences in numbers of stabilizing host-guest contacts

available in these hosts.

∆E ) E_(complex)- [E_(host)+ E_(guest)

]

and are listed in Table 4 for both the gas phase and in

CHCl₃solution (with GB/SA⁵chloroform treatment).

Gas phase calculations were also performed to estimate

the activation energies for guest escape following a

procedure described earlier.^10,11A reaction coordinate,

λ, was defined along which the guest was forced to pass

through the larger of the equatorial portals.¹¹As il-

lustrated in Figure 4, the dotted lines connect a dummy

atom (Du) with the four aryl carbon atoms 20 Å distant

attached to the two interhemispheric bridges that define

The gas phase transition state energies for complex-

ation-decomplexation differ dramatically, that for

7-Me.NMP being ≈ 12 kcal mol^-1higher than that for

8-Me.NMP, which in turn is 5.8 kcal mol^-1higher than

that for 10-Me.NMP. This order correlates with the

order listed in Table 3 for the t_1/2values for the decom-

plexations of the same hosts as follows: 7.guests >

8.guests > 10.guests. Thus the differences between the

kinetic stabilities of the three hemicarceplexes are much

greater than the differences in thermodynamic stabilities.

Striking features of the energy-distance profile for

decomplexation of the three model hosts shown in Figure

(13) Still, W. C.; Tempczyk, A.; Hawley, R. C.; Hendrickson, T. J .

Am. Chem. Soc. 1990, 112, 6127-6129.

(14) Cram, D. J .; Blanda, M. T.; Paek, K.; Knobler, C. B. J . Am.

Chem. Soc. 1992, 114, 7765-7773.

9334 J . Org. Chem., Vol. 61, No. 26, 1996

Yoon et al.

F igu r e 4. Definition of reaction coordinate λ for activation energy calculations. See text.

membered ring portals (8-Me.NMP, 10-Me.NMP),

which spread over 6-7 Å. In earlier studies,^10-12we

proposed an alternative mechanism involving the inter-

conversions of the intrahemispheric spanners of hemi-

carcerands from chairlike to boatlike conformations to

explain the escape pathway of acetonitrile molecules from

the tetrasulfide hemicarceplex.¹¹This gating phenom-

enon also plays an important role in obtaining stable

complexes.¹²The conversion of the intrahemispheric

spanners from low-energy chairlike to higher-energy

boatlike conformations enlarges the portals and reduces

the steric repulsion between host and guest. This is

especially true when the interhemispheric bridges are

short (for example, 20-membered ring portals). When the

interhemispheric bridges are longer, the methylene gate

plays a less important role. The size and shape of the

guest molecule also affect the importance of the gating

mechanism. In the present case, the steric repulsive

energy reduced by the gating process is approximately

equal to the energy cost for the host to adopt the higher-

energy conformation.

F igu r e 5. Energy profile for the decomplexation of the NMP

guest in vacuum. 9: 7-Me.NMP; [: 8-Me.NMP; 0, 10-

Me.NMP.

5 are as follows: (1) the energy falls very abruptly at a

distance of about 14 Å, particularly for 7-Me.NMP; (2)

the curves contain some fine structure and several

maxima; (3) the energy peaks spread over 5-6 Å for all

three complexes. All three features correlate with what

is suggested by the mechanical force and deformations

needed to separate host from guest in CPK models of

these complexes. Large numbers of bond angles must

be adjusted, particularly in the host, to synchronize with

guest rotations and with guest penetrations and expan-

sions of the portals. The distance the guest must travel

before it is free of the expanded portal in CPK models is

in the 5-7 Å range. Even multiple mechanical barriers

are encountered in these model separations.

Although hosts with longer fourth bridges ((CH₂)₅and

1,3-(CH₂)₂C₆H₄) than (CH₂)₄do not have significantly

greater inner volumes (as seen in Table 4, the stabiliza-

tion energies for 7-Me.NMP, 8-Me.NMP, and 10-

Me.NMP are very similar), the two portals that flank

the longer fourth bridges dramatically increase in size

and conformational adaptivity for guest passages. The

portal effect can be seen in Figure 5, where the energy

peak for 7-Me.NMP (26-membered ring portals) is

somewhat sharper and narrower than the peaks for 27-

The greatest weaknesses of the activation energy

calculations are the omissions of solvent and entropy. In

an earlier study, the decomplexation rate for 12.DMA¹⁴

was found to vary by a factor of about 50 as solvent was

changed from C₆D₅Br to C₆D₅CD₃. Free energies, en-

thalpies, and entropies of activation for decomplexation

of 12.DMA, 12.MeCO₂CH₂Me, 12.MeCOCH₂Me, and

12.MeC₆H₅in 1,2-(CD₃)₂C₆D₄were measured at 100 °C.

The contributions of ∆S^‡to the ∆G^‡for the four complexes

varied from 25 to 51%. The contribution of constrictive

binding to the free energies of activation for decomplex-

ations of the four complexes varied from 82 to 88%. Host

12 has four 26-membered ring portals as does 7, but each

OCH₂C₆H₄CH₂O bridge in 12 is conformationally less

adaptive than each O(CH₂)₄O bridge in 7. Clearly, much

exploration of decomplexation phenomena remains to be

done.

Su m m a r y. Seven new carcerand or hemicarcerand

systems have been synthesized, all of which contain two

rigid bowls connected by three O(CH₂)₄O bridges put in

Seven New Hemicarcerands

J . Org. Chem., Vol. 61, No. 26, 1996 9335

28H ,53H ,55H -b is[1,3]b en zod ioxocin o[9,8-d :9′,8′-d ′]b is-

[1,3]ben zod ioxocin o[9′,10′:17,18;l0′′,9′′:25,26][1,3,6,11,14,

16,19,24]oct a oxa cycloh exa cosin o[4,5-j:13,12-j′]b is[1,3]-

ben zod ioxocin -65,72-d iol, Ster eoisom er 2. Into a 1 L one-

neck round-bottom flask equipped with a magnetic stirrer and

blanketed with argon were placed 1 g (1.0 mmol) of 1, 200 mL

of degassed NMP, and 6.5 g of Cs₂CO₃. The reaction mixture

was stirred at 25 °C for 1 min after which 0.97 g (4.0 mmol) of

1,4-butanediol dimesylate was added. The mixture was stirred

for 16-18 h and then poured into 500 mL of 10% NaCl (aq).

After 30 min, the precipitate that formed was filtered and

chromatographed with 0.5% EtOAc in CH₂Cl₂followed by 3%

EtOAc in CH₂Cl₂to give 2 (30-40%): ¹H NMR δ 1.98 (4 H, br

s); 2.03 (8 H, br s); 2.48 (16 H, m); 2.68 (16 H, m); 3.88 (4 H,

br s); 3.92 (8 H, br s); 4.26 (8 H, overlapping d, J ) 8.1 Hz);

4.82 (8 H, m); 5.85 (4 H, d, J ) 7.0 Hz); 5.97 (4 H, d, J ) 6.9

Hz); 6.21 (2 H, s); 6.64 (2 H, s); 6.82 (4 H, s); 6.85 (2 H, s); 7.16

(16 H, m); 7.23 (24 H, m); FAB MS m/ e (2194.9, M⁺), 2197.1

(100). Anal. Calcd for C₁₄₀H₁₃₀O₂₄^.5H₂O: C, 73.54; H, 6.17.

Found: C, 73.67; H, 6.04.

8,9,10,11,39,40,41,42-Octa h yd r o-1,18,26,28,53,55,63,77-

octaph en eth yl-34,47-(epoxybu tan oxy)-20,24:57,61-dim eth -

a n o-2,52:17,29-d im eth en o-3,51,16,30-(m eth yn oxym eth a -

n o x y m e t h y n o )-1H ,18H ,26H ,28H ,53H ,55H -b i s [1,3]-

ben zod ioxocin o[9,8-d :9′,8′-d ′]bis[1,3]ben zod ioxocin o[9′,

10′:17,18;10′′,9′′:25,26][1,3,6,11,14,16,19,24]oct a oxa cyclo-

h exa cosin o[4,5-j:13,12-j′]bis[1,3]ben zod ioxocin , Ster eo-

isom er 4.NMP . P r oced u r e A. Diol host 2⁴(100 mg, 0.045

mmol), 50 mL of NMP, 1 g of pulverized Cs₂CO₃, and 30 µL

(0.46 mmol) of BrCH₂Cl were stirred at 65 °C for 24 h, and 30

µL (0.46 mmol) of BrCH₂Cl was added. After stirring at 65

°C for another 24 h, the solvent was removed in vacuo and

the residue dissolved in CHCl₃. The remaining solids were

filtered through a 1 cm pad of Celite, and the solvent was

rotary evaporated to ∼3 mL volume and poured into 100 mL

of methanol. The precipitate that formed was filtered and

chromatographed on a preparative TLC plate with CHCl₃to

give 55 mg (53%) of 4.NMP: ¹H NMR δ -1.25 (2 H, q); -1.13

(3 H, s); -0.90 (2 H, t, J ) 7.2 Hz); 1.80 (2 H, t, J ) 7.0 Hz);

1.95 (4 H, br s); 1.97 (4 H, br s); 2.17 (4 H, br s); 2.49 (16 H,

m); 2.67 (16 H, m); 3.89 (4 H, br s); 3.94 (4 H, t); 4.01 (4 H, t,

J ) 7.1 Hz); 4.24 (4 H, d, J ) 7.1 Hz); 4.42 (4 H, d, J ) 7.1

Hz); 4.86 (8 H, m); 5.79 (4H, d, J ) 7.3 Hz); 6.05 (4H, d, J )

7.3 Hz); 6.46 (2 H, s); 6.84 (6 H, s); 6.89 (2 H, s); 7.15 (16 H,

m); 7.23 (24 H, m); FAB MS, m/ e (2306.0, M⁺), 2307.0 (100).

Anal. Calcd for C₁₄₆H₁₃₉NO₂₅: C, 75.99; H, 6.07. Found: C,

76.23; H, 5.75.

4.DMSO. Application of procedure A to 100 mg (0.045

mmol) of diol host 2, 50 mL of DMSO, 1 g of Cs₂CO₃, and 60

µL (0.92 mmol) of BrCH₂Cl gave 52 mg (51%) of 4.DMSO:

¹H NMR δ -0.68 (6 H, s); 1.95-2.19 (12 H, m); 2.49 (16 H,

m); 2.68 (16 H, m); 3.82 (4 H, t, J ) 7.1 Hz); 3.91 (4 H, br s);

3.97 (4 H, t, J ) 7.1 Hz); 4.13 (4 H, d, J ) 7.3 Hz); 4.32 (4 H,

d, J ) 7.3 Hz); 4.86 (8 H, m); 5.85 (4H, d, J ) 7.3 Hz); 6.09

(4H, d, J ) 7.3 Hz); 6.54 (2 H, s); 6.80 (2 H, s); 6.84 (4 H, s);

6.92 (2 H, s); 7.17 (16 H, m); 7.24 (24 H, m); FAB MS m/ e

(2284.9, M⁺), 2287.1 (40); 2209 (100). Anal. Calcd for

C₁₄₃H₁₃₆O₂₅S: C, 75.11; H, 5.99. Found: C, 75.36; H, 5.98.

4.DMA. Application of procedure A to 100 mg (0.045

mmol) of diol host 2, 50 mL of DMA, 1 g of Cs₂CO₃, and 60 µL

(0.92 mmol) of BrCH₂Cl gave 56 mg of 4.DMA (54%): ¹H NMR

δ -1.92 (3 H, s); -0.90 (3 H, s); 1.58 (3 H, s); 1.85-2.22 (12 H,

m); 2.49 (16 H, m); 2.68 (16 H, m); 3.82 (4 H, t, J ) 6.9 Hz);

3.92 (4 H, br s); 4.00 (4 H, t, J ) 6.9 Hz); 4.16 (4 H, d, J ) 7.2

Hz); 4.54 (4 H, d, J ) 7.2 Hz); 4.85 (8 H, m); 5.81 (4H, d, J )

7.2 Hz); 6.05 (4H, d, J ) 7.2 Hz); 6.47 (2 H, s); 6.77 (2 H, s);

6.83 (4 H, s); 6.92 (2 H, s); 7.17 (16 H, m); 7.24 (24 H, m); FAB

MS m/ e (2294.0, M⁺) 2295.3 (30), 2208.3 (100). Anal. Calcd

for C₁₄₅H₁₃₉NO₂₅: C, 75.86; H, 6.10. Found: C, 76.09; H, 6.37.

4.1,4-Me₂C₆H₄. P r oced u r e B. Into a Pyrex test tube

capped with a rubber septum were placed 30 mg (0.013 mmol)

of 4.DMA and 1 mL of p-xylene. This mixture was heated at

140 °C for 3 days and poured into 50 mL of methanol. The

precipitate that formed was filtered and chromatographed on

a preparative TLC plate with CHCl₃to give 26 mg (85%) of

4.1,4-Me₂C₆H₄: ¹H NMR δ -2.02 (6 H, s); 1.09 (4 H, m); 2.08

place by a shell closure. In a separate step, a fourth

unique bridge was introduced by sealing into the host’s

inner phase appropriately sized guests in the medium.

Three of the unique bridges are shorter (OCH₂O,

O(CH₂)₂O, and O(CH₂)₃O), one is about the same length

(2,3-(OCH₂)₂quinoxaline), and three are longer (O(CH₂)₅O,

1,3-(OCH₂)₂C₆H₄, and 2,6-(OCH₂)₂pyridine) than the

other three bridges. Thirty-six new hemicarceplexes,

involving thirteen different guests, were prepared either

by sealing in or by thermally-induced guest exchange

driven by mass law. They were characterized, and their

¹H NMR spectral changes were correlated with changes

in the fourth bridge. The crystal structures of two

complexes were determined and compared with expecta-

tions based on molecular model examinations. Force field

AMBER* calculations were made of the structures of four

NMP complexes containing homologously related unique

bridges (O(CH₂)_nO, n ) 1-4) and were similar to those

based on crystal structures of similar hemicarceplexes.

Half-lives for decomplexations of hemicarceplexes involv-

ing three of the largest hosts and guests were correlated

with portal macroring sizes. Decomplexations were

modeled with AMBER* force field calculations and the

results found to qualitatively correlate with experimental

facts.

Exp er im en ta l Section

Gen er a l. All chemicals were reagent grade and used

directly unless otherwise noted. Dimethylacetamide (DMA),

N-methylpyrrolidinone (NMP), and dimethyl sulfoxide (DMSO)

were stored over (24 h heated at 320 °C) 3-Å molecular sieves

and degassed under high vacuum just before use. A 360-MHz

spectrometer was used to record ¹H NMR spectra unless

otherwise noted. Spectra taken in CDCl₃were referenced to

residual CHCl₃at 7.26 ppm. FAB MS were determined on a

ZAB SE instrument with 3-nitrobenzyl alcohol (NOBA) as a

matrix and Xe as carrier gas. Gravity chromatography was

performed on silica gel 60 (70-230 mesh). Thin-layer chro-

matography involved glass-backed plates (silica gel 60, F₂₄₅

0.25 mm).

,

8,9,10,11,39,40,41,42-Octa h yd r o-1,18,26,28,53,55,63,74-

octaph en eth yl-34,47-(epoxybu tan oxy)-20,24:57,61-dim eth -

a n o -2,52:3,51:16,30:17,29-t e t r a m e t h e n o -1H ,18H ,26H ,

9336 J . Org. Chem., Vol. 61, No. 26, 1996

Yoon et al.

(4 H, m); 2.17 (4 H, m); 2.52 (16 H, m); 2.69 (16 H, m); 2.93 (4

H, t); 3.92 (4 H, br s); 4.24 (8 H, t, J ) 7.8 Hz); 4.27 (4 H, t);

4.89 (8 H, m); 5.82 (4H, d, J ) 6.9 Hz); 5.85 (4 H, s); 5.89 (4H,

d, J ) 6.9 Hz); 6.82 (4 H, s); 6.88 (2 H, s); 6.94 (2 H, s); 7.16

(16 H, m); 7.23 (24 H, m); FAB MS, m/ e (2313.0, M⁺) 2314.0

(40), 2208.3 (100). Anal. Calcd for C₁₄₉H₁₄₀O₂₄‚2H₂O: C,

76.13; H, 6.17. Found: C, 76.14; H, 5.99.

70 mg (0.18 mmol) more of 1,3-propanediol ditosylate was

added. After stirring at 75 °C for another 24 h, the mixture

was poured into 50 mL of 5% NaCl (aq). The precipitate that

formed was filtered, washed with methanol, and chromato-

graphed on a preparative TLC plate with CHCl₃to give 46

mg (46%) of 6 (empty): ¹H NMR δ 1.99 (12 H, br s); 2.22 (2 H,

m); 2.51 (16 H, m); 2.67 (16 H, m); 3.90 (12 H, m); 4.18 (4 H,

t, J ) 7.1 Hz); 4.30 (8 H, d, J ) 7.8 Hz); 4.81 (8 H, t, J ) 7.8

Hz); 5.78 (4 H, d, J ) 7.3 Hz); 5.82 (4 H, d, J ) 7.3 Hz); 6.82

(8 H, m); 7.12 (16 H, m); 7.23 (24 H, m); FAB MS, m/ e (2234.9,

M⁺), 2237.5 (100). Anal. Calcd for C₁₄₃H₁₃₄O₂₄‚2H₂O: C,

75.57; H, 6.12. Found: C, 75.62; H, 6.09.

8,9,10,11,39,40,41,42-Octa h yd r o-1,18,26,28,53,55,63,78-

octaph en eth yl-34,47-(epoxybu tan oxy)-20,24:57,61-dim eth -

a n o-2,52:17,29-d im et h en o-3,51,16,30-(m et h yn oxyet h a n -

oxym et h yn o)-1H ,18H ,26H ,28H ,53H ,55H -b is[1,3]b en zo-

d ioxocin o[9,8-d :9′,8′-d ′]b is[1,3]b e n zod ioxocin o[9′,10′:

17,18;10′′,9′′:25,26][1,3,6,11,14,16,19, 24]octa oxa cycloh exa -

cosin o[4,5-j:13,12-j′]bis[1,3]ben zod ioxocin , Ster eoisom er

5.NMP . P r oced u r e C. A mixture of diol 2 (100 mg, 0.045

mmol), 50 mL of NMP, 1 g of Cs₂CO₃, and 33 mg (0.09 mmol)

of 1,2-ethanediol ditosylate was stirred at 75 °C for 24 h, and

a second portion of 66 mg (0.18 mmol) of 1,2-ethanediol

ditosylate was added. After stirring at 75 °C for another 24

h, the solvent was removed in vacuo and the residue was

dissolved in CHCl₃. The remaining solids were filtered

through a 1 cm pad of Celite and the solvent was rotary

evaporated, concentrated to ∼3 mL, and poured into 100 mL

of methanol. The precipitate that formed was filtered and

chromatographed on a preparative TLC plate with CHCl₃to

give 47 mg (45%) of 5.NMP: ¹H NMR δ -0.93 (2 H, q); -0.89

(3 H, s); -0.72 (2 H, t); 1.99 (12 H, m); 2.51 (16 H, m); 2.67 (16

H, m); 3.95 (8 H, br s); 4.06 (4 H, br s); 4.21 (4 H, d, J ) 7.0

Hz); 4.42 (4 H, d, J ) 7.0 Hz); 4.54 (4 H, s); 4.81 (8 H, m); 6.05

(4H, d, J ) 7.3 Hz); 6.80 (2 H, s); 6.83 (4 H, s); 6.87 (2 H, s);

7.12 (16 H, m); 7.24 (24 H, m); FAB MS, m/ e (2320.0, M⁺)

2320.2, (100). Anal. Calcd for C₁₄₇H₁₄₁NO₂₅: C, 76.05; H, 6.12.

Found: C, 76.09; H, 6.06.

5.DMSO. Application of procedure C to 100 mg (0.045

mmol) of diol 2, 15 mL of DMSO, 1 g of Cs₂CO₃, and 99 mg

(0.27 mmol) of 1,2-ethanediol ditosylate gave 42 mg (41%) of

5.DMSO after preparative TLC: ¹H NMR δ -0.48 (6 H, s);

2.02 (12 H, br s); 2.47 (16 H, m); 2.68 (16 H, m); 3.95 (8 H, br

s); 4.04 (4 H, br s); 4.12 (4 H, d, J ) 7.1 Hz); 4.28 (4 H, d, J )

7.1 Hz); 4.54 (4 H, s); 4.84 (8 H, m); 5.86 (8 H, t, J ) 7.6 Hz);

6.78 (2 H, s); 6.85 (4 H, s); 6.89 (2 H, s); 7.17 (16 H, m); 7.23

(24 H, m); FAB MS, m/ e (2298.9, M⁺) 2301.4 (100), 2222.8

(30). Anal. Calcd for C₁₄₄H₁₃₈O₂₅S: C, 75.18; H, 6.05.

Found: C, 75.08; H, 6.05.

5.DMA. Application of procedure C to 100 mg (0.045

mmol) of diol 2, 20 mL of DMA, 1 g of Cs₂CO₃, and 99 mg

(0.27 mmol) of 1,2-ethanediol ditosylate gave 44 mg (42%) of

5.DMA after preparative TLC: ¹H NMR δ -1.67 (3 H, s);

-0.56 (3 H, s); 1.64 (3 H, s); 1.96 (12 H, m); 2.48 (16 H, m);

2.67 (16 H, m); 3.92 (8 H, t, br s); 4.01 (4 H, br s); 4.14 (4 H,

d, J ) 7.1 Hz); 4.45 (4 H, d, J ) 7.1 Hz); 4.65 (4 H, s); 4.83 (8

H, m); 5.81 (8H, t, J ) 6.4 Hz); 6.75 (2 H, s); 6.83 (4 H, s); 6.89

(2 H, s); 7.16 (16 H, m); 7.22 (24 H, m); FAB MS, m/ e (2308.0,

M⁺), 2309.7 (100). Anal. Calcd for C₁₄₆H₁₄₁NO₂₅: C, 75.92;

H, 6.15. Found: C, 75.87; H, 5.96.

5.1,4-Me₂C₆H₄. Application of procedure B to 30 mg (0.013

mmol) of 5.DMA and 1 mL of p-xylene gave after preparative

TLC with CHCl₃25 mg (88%) of 5.1,4-Me₂C₆H₄: ¹H NMR δ

-1.93 (6 H, s); 1.21 (4 H, m); 2.10 (8 H, m); 2.52 (16 H, m);

2.70 (16 H, m); 3.09 (4 H, t); 4.03 (4 H, br s); 4.11 (4 H, d, J )

6.9 Hz); 4.17 (4 H, d, J ) 6.9 Hz); 4.18 (4 H, s); 4.21 (4 H, t);

4.86 (8 H, m); 5.69 (4H, d, J ) 6.9 Hz); 5.78 (4H, d, J ) 6.9

Hz); 5.97 (4 H, s); 6.82 (2 H, s); 6.85 (2 H, s); 6.94 (4 H, s); 7.17

(16 H, m); 7.23 (24 H, m); FAB MS, m/ e (2327.0, M⁺), 2329.7

(100), 2224.0 (90). Anal. Calcd for C₁₅₀H₁₄₂O₂₄: C, 77.37; H,

6.15. Found: C, 77.68; H, 5.98.

6.NMP . Application of procedure C to 100 mg (0.045

mmol) of diol 2, 50 mL of NMP, 1 g of Cs₂CO₃, and 35 mg (0.09

mmol) of 1,3-propanediol ditosylate (first portion) and 70 mg

(0.18 mmol) of 1,3-propanediol ditosylate (second portion) gave

after preparative TLC with CHCl₃67 mg (64%) of 6.NMP:

¹H NMR δ -0.90 (3 H, s); -0.82 (2 H, q); -0.60 (2 H, t); 1.98

(12 H, br s); 2.22 (2 H, m); 2.48 (16 H, m); 2.65 (16 H, m); 3.98

(12 H, m); 4.18 (4 H, t, J ) 7.1 Hz); 4.21 (4 H, d, J ) 7.6 Hz);

4.41 (4 H, d, J ) 7.6 Hz); 4.85 (8 H, t, J ) 7.8 Hz); 5.81 (8 H,

t, J ) 7.3 Hz); 6.85 (8 H, m); 7.13 (16 H, m); 7.23 (24 H, m);

FAB MS, m/ e (2334.0, M⁺), 2336.0 (100). Anal. Calcd for

C₁₄₈H₁₄₃NO₂₅: C, 76.11; H, 6.17. Found: C, 76.17; H, 6.17.

6.DMSO. Application of procedure C to 100 mg (0.045

mmol) of diol host 2, 50 mL of DMSO, 1 g of Cs₂CO₃, and 105

mg (0.27 mmol) of 1,3-propanediol ditosylate gave 62 mg (60%)

of 6.DMSO after preparative TLC with CHCl₃: ¹H NMR δ

-0.51 (6 H, s); 2.03 (12 H, br s); 2.25 (2 H, m); 2.50 (16 H, m);

2.69 (16 H, m); 3.94 (12 H, m); 4.19 (4 H, t); 4.21 (8 H, t); 4.84

(8 H, t, J ) 7.8 Hz); 5.83 (4 H, d, J ) 7.3 Hz); 5.88 (4 H, d, J

) 7.3 Hz); 6.84 (8 H, m); 7.15 (16 H, m); 7.24 (24 H, m); FAB

MS, m/ e (2312.9, M⁺), 2315.4 (100). Anal. Calcd for

C₁₄₅H₁₄₀O₂₅S: C, 75.24; H, 6.10. Found: C, 75.31; H, 6.10.

6.DMA. Application of procedure C to 100 mg (0.045

mmol) of diol 2, 50 mL of DMA, 1 g of Cs₂CO₃, and 105 mg

(0.27 mmol) of 1,3-propanediol ditosylate gave 67 mg (64%) of

6.DMA after preparative TLC with CHCl₃: ¹H NMR δ -1.68

(3 H, s); -0.53 (3 H, s); 2.01 (12 H, br s); 2.25 (2 H, m); 2.49

(16 H, m); 2.68 (16 H, m); 3.91 (12 H, m); 4.20 (8 H, d, J ) 7.2

Hz); 4.39 (4 H, d, J ) 7.4 Hz); 4.84 (8 H, t, J ) 7.9 Hz); 5.81

(4 H, d, J ) 7.5 Hz); 5.84 (4 H, d, J ) 7.5 Hz); 6.82 (2 H, s);

6.84 (4 H, s); 6.87 (2 H, s); 7.15 (16 H, m); 7.24 (24 H, m );

FAB MS, m/ e (2322.0, M⁺), 2323.7 (100). Anal. Calcd for

C₁₄₇H₁₄₃NO₂₅: C, 75.98; H, 6.20. Found: C, 76.16; H, 6.03.

6.1,4-Me₂C₆H₄. Application of procedure B to 30 mg (0.013

mmol) of 6 (empty) and 1 mL of p-xylene gave after preparative

TLC with CHCl₃27 mg (90%) of 6.1,4-Me₂C₆H₄: ¹H NMR δ

-2.01 (6 H, s); 1.67 (4 H, br s); 1.97 (2 H, m); 2.09 (8 H, br s);

2.52 (16 H, m); 2.70 (16 H, m); 3.36 (4 H, t, J ) 6.9 Hz); 3.66

(4 H, br s); 4.12 (8 H, hidden); 4.12 (4 H, d, J ) 6.9 Hz); 4.18

(4 H, d, J ) 6.9 Hz); 4.87 (8 H, t, J ) 7.8 Hz); 5.71 (8 H, dd,

J ) 7.0 Hz); 5.94 (4H, s); 6.85 (4 H, s); 6.94 (4 H, s); 7.16 (16

H, m); 7.23 (24 H, m); FAB MS, m/ e (2341.0, M⁺), 2342 (100),

2236 (50). Anal. Calcd for C₁₅₁H₁₄₄O₂₄: C, 77.41; H, 6.20.

Found: C, 77.29; H, 6.12.

8,9,10,11,40,41,42,43-Octa h yd r o-1,18,26,28,54,56,64,81-

octaph en eth yl-34,48-(epoxybu tan oxy)-20,24:58,62-dim eth -

a n o-2,53:17,29-d im et h en o-3,52,16,30-(m et h yn oxyb u t a n -

oxym e t h yn o)-1H ,18H ,26H ,28H ,39H ,54H ,56H -b is[1,3]-

b e n zod ioxocin o[9,8-d :9′,8′-d ′]b is[1,3]b e n zod ioxocin o-

[9′,10′:4,5;10′′,9′′:12,13][1,3,6,11,14,16,19,25]octa oxa cyclo-

h ep ta cosin o[17,18-j:27,26-j′]bis[1,3]ben zod ioxocin , Ste-

r eoisom er 8.CHCl₃. A mixture of 100 mg (0.045 mmol) of

diol 2, 50 mL of NMP, 1 g of Cs₂CO₃, and 36 mg (0.09 mmol)

of 1,5-pentanediol dimesylate was stirred at 25 °C for 5 h, and

then the temperature was raised to 50 °C and the mixture

stirred for 24 h. The solution was stirred for another 24 h

after the addition of 36 mg (0.09 mmol) of 1,5-pentanediol

dimesylate. The product was isolated as in procedure A to

give after preparative TLC with CHCl₃81 mg (79%) of

8.CHCl₃: ¹H NMR δ 1.82 (6 H, m); 1.97 (12 H, br s); 2.49 (16

H, m); 2.68 (16 H, m); 3.88 (4 H, m); 3.97 (12 H, br s); 4.20 (4

H, d, J ) 7.0 Hz); 4.23 (4 H, d, J ) 7.0 Hz); 4.83 (8 H, m); 5.81

(4 H, d, J ) 6.9 Hz); 5.86 (4 H, d, J ) 6.9 Hz); 6.80 (2 H, s);

6.82 (2 H, s); 6.84 (4 H, s); 7.17 (16 H, m); 7.23 (24 H, m); FAB

8,9,10,11,39,40,41,42-Octa h yd r o-1,18,26,28,53,55,63,79-

octaph en eth yl-34,47-(epoxybu tan oxy)-20,24:57,61-dim eth -

a n o-2,52:17,29-d im eth en o-3,51,16,30-(m eth yn oxyp r op a n -

oxym e t h yn o)-1H ,l8H ,26H ,28H ,53H ,55H -b is[1,3]b e n zo-

d ioxocin o[9,8-d :9′,8′-d ′]b is[1,3]b e n zod ioxocin o[9′,10′:

17,18;10′′,9′′:25,26][1,3,6,11,14,16,19, 24]octa oxa cycloh exa -

cosin o[4,5-j:13,12-j′]bis[1,3]ben zod ioxocin , Ster eoisom er

6 (Em p ty). P r oced u r e D. A mixture of diol 2 (100 mg (0.045

mmol), 10 mL of HMPA, 1 g of Cs₂CO₃, and 35 mg (0.09 mmol)

of 1,3-propanediol ditosylate was stirred at 75 °C for 24 h, and

Seven New Hemicarcerands

J . Org. Chem., Vol. 61, No. 26, 1996 9337

MS, m/ e (2380.9, M⁺), 2384.0 (100), 2264.6 (98). Anal. Calcd

for C₁₄₆H₁₃₉Cl₃O₂₄: C, 73.56; H, 5.88. Found: C, 73.58; H, 5.60.

8.2-HOC₆H₄Me. Application of procedure G to 30 mg

(0.013 mmol) of 8.CHCl₃and 1 mL of o-cresol gave, after

preparative TLC with CHCl₃, 28 mg (90%) of 8.2-HOC₆H₄-

Me: ¹H NMR δ -1.68 (3 H, s); 1.68-2.04 (18 H, m); 2.51 (16

H, m); 2.69 (16 H, m); 3.22 (1 H, t); 3.68-4.10 (16 H, m); 4.15

(2 H, d, J ) 7.1 Hz); 4.29 (4 H, d, J ) 7.7 Hz); 4.36 (2 H, d, J

) 7.1 Hz); 4.84 (8 H, m); 5.63 (2 H, d, J ) 7.1 Hz); 5.73 (2 H,

d, J ) 7.1 Hz); 5.78 (2 H, d, J ) 7.0 Hz); 5.83 (2 H, d, J ) 7.0

Hz); 5.98 (2 H, d); 6.14 (2 H, d); 6.21 (2 H, s); 6.71-7.08 (8 H,

m); 7.17 (16 H, m); 7.23 (24 H, m); FAB MS m/ e (2371.0, M⁺)

2372, (100), 2265 (80). Anal. Calcd for C₁₅₂H₁₄₆O₂₅: C, 76.94;

H, 6.20. Found: C, 76.98; H, 6.23.

8.CHCl₂CHCl₂. Application of procedure B to 30 mg

(0.013 mmol) of 8.CHCl₃and 1 mL of tetrachloroethane gave

after preparative TLC with CHCl₃28 mg (92%) of 8.CHCl₂-

CHCl₂: ¹H NMR δ 1.80 (6 H, m); 1.97 (12 H, br s); 2.49 (16 H,

m); 2.69 (16 H, m); 3.88 (4 H, m); 3.98 (12 H, br s); 4.29 (2 H,

s); 4.35 (8 H, dd); 4.82 (8 H, m); 5.78 (4 H, d, J ) 7.1 Hz); 5.83

(4 H, d, J ) 7.1 Hz); 6.79 (2 H, s); 6.82 (2 H, s); 6.84 (4 H, s);

7.17 (16 H, m); 7.22 (24 H, m); FAB MS, m/ e (2428.8, M⁺),

2431 (100), 2263 (60). Anal. Calcd for C₁₄₇H₁₄₀Cl₄O₂₄^.3H₂O:

C, 71.01; H, 5.92. Found: C, 70.74; H, 5.74.

6,34,35,36,37,65-H e xa h yd r o-13,21,23,48,50,76,84-oc-

ta p h en eth yl-29,42-(ep oxybu ta n oxy)-15,19:52,56-d im eth -

a n o-12,24:47,59-d im et h en o-11,25,46,60-(m et h yn oxyb u -

t a n oxym e t h yn o)-13H ,21H ,23H ,48H ,50H ,58H -b is[1,3]-

b e n z o d i o x o c i n o [9′,10′:4,5;10′′,9′′:12,13]b i s [1,3]b e n -

z o d i o x o c i n o [9′′,8′′:4′,5′][1,3]b e n z o d i o x o c i n o [9′,10′:

17,18;10′′,9′′:25,26][1,3,6,11,14,16,19, 24]octa oxa cycloh exa -

cosin o[8,9-b]q u in oxa lin e, St er eoisom er 9.NMP . P r o-

ced u r e E. A mixture of 100 mg (0.045 mmol) of diol 2, 50

mL of NMP, 1 g of Cs₂CO₃, and 20 mg (0.09 mmol) of 2,3-bis-

(bromomethyl)quinoxaline was stirred at 25 °C for 5 h, and

then the temperature was raised to 50 °C and the mixture

was stirred for 24 h. The solution was stirred for another 24

h after the addition of 20 mg (0.09 mmol) of 2,3-bis(bromo-

methyl)quinoxaline. The remaining solids were filtered through

a 1 cm pad of Celite, and the solvent was rotary evaporated

and concentrated to ∼3 mL and poured into 100 mL of

methanol. The precipitate that formed was filtered and

chromatographed on a preparative TLC plate with CHCl₃to

give 86 mg (78%) of 9.NMP: ¹H NMR δ -1.17 (3 H, s); -1.15

(2 H, q); -0.96 (2 H, t); 1.80 (2 H, t); 1.97 (12 H, m); 2.47 (16

H, m); 2.66 (16 H, m); 3.92 (12 H, br s); 4.14 (4 H, d, J ) 7.3

Hz); 4.38 (4 H, d, J ) 7.3 Hz); 4.71 (4 H, t, J ) 7.7 Hz); 4.82

(4 H, t, J ) 7.7 Hz); 5.44 (4 H, s); 5.76 (8 H, d, J ) 7.2 Hz);

6.81 (4 H, s); 6.84 (2 H, s); 6.93 (2 H, s); 7.15 (16 H, m); 7.23

(24 H, m); 7.77 (2 H, m); 8.08 (2 H, m); FAB MS, m/ e (2448.0,

8.1,4-(MeO)₂C₆H₄. P r oced u r e F . Into a Pyrex test tube

capped with a rubber septum were placed 30 mg (0.013 mmol)

of 8.CHCl₃, 180 mg of 1,4-dimethoxybenzene (1.3 mmol), and

1 mL of Ph₂O. This mixture was heated at 165 °C for 3 d and

poured into 50 mL of methanol. The precipitate that formed

was filtered (without further purification) to give 28 mg (90%)

of 8.1,4-(MeO)₂C₆H₄: ¹H NMR δ -0.41 (6 H, s); 1.56 (6 H, br

s); 1.81 (8 H, br s); 2.03 (4 H, br s); 2.50 (16 H, m); 2.69 (16 H,

m); 3.58 (4 H, m); 3.62 (4 H, m); 4.04 (4 H, br s); 4.08 (4 H, br

s); 4.28 (8 H, t, J ) 7.1 Hz); 4.90 (8 H, t, J ) 7.7 Hz); 5.74 (8

H, t, J ) 7.0 Hz); 5.84 (4 H); 6.82 (4 H, s); 6.85 (2 H, s); 6.86

(2 H, s); 7.17 (16 H, m); 7.24 (24 H, m); FAB MS, m/ e (2401.0,

M⁺), 2402.6 (100). Anal. Calcd for C₁₅₃H₁₄₈O₂₆^.H₂O: C, 75.91;

H, 6.25. Found: C, 76.10; H, 5.90.

8.1,3-(MeO)₂C₆H₄. P r oced u r e G. Into a Pyrex test tube

capped with a rubber septum were placed 30 mg (0.013 mmol)

of 8.CHCl₃and 1 mL of 1,3-dimethoxybenzene. This mixture

was heated at 165 °C for 3 d and poured into 50 mL of

methanol. The precipitate that formed was filtered and

chromatographed on a preparative TLC plate with CHCl₃to

give 28 mg (89%) of 8.1,3-(MeO)₂C₆H₄: ¹H NMR δ -0.55 (6

H, s); 1.53 (6 H, br s); 1.87 (8 H, br s); 2.03 (4 H, br s); 2.50 (16

H, m); 2.70 (16 H, m); 3.55 (4 H, m); 3.60 (4 H, m); 4.09 (8 H,

br s); 4.33 (8 H, t, J ) 6.3 Hz); 4.92 (8 H, m); 5.02 (2 H, d);

5.48 (1 H, s); 5.74 (8 H, t, J ) 6.0 Hz); 6.82 (4 H, s); 6.86 (2 H,

s); 6.92 (2 H, s); 7.18 (16 H, m); 7.24 (24 H, m); FAB MS, m/ e

(2401.0, M⁺), 2402.6 (100). Anal. Calcd for C₁₅₃H₁₄₈O₂₆: C,

76.48; H, 6.21. Found: C, 76.31; H, 6.05.

M⁺), 2450.7 (100), 2351.0 (60). Anal. Calcd for C₁₅₅H₁₄₅

-

N₃O₂₅: C, 75.99; H, 5.97; N, 1.72. Found: C, 76.09; H, 6.13;

N, 1.63.

8.1,2-(MeO)₂C₆H₄. Application of procedure G to 8.CHCl₃

(30 mg, 0.013 mmol) and 1 mL of 1,2-(MeO)₂C₆H₄gave, after

preparative TLC with CHCl₃, 26 mg (86%) of 8.1,2-

(MeO)₂C₆H₄: ¹H NMR δ 1.62 (8 H, br s); 1.78 (6 H, br s); 2.04

(4 H, br s); 2.50 (16 H, m); 2.68 (16 H, m); 3.60 (4 H, br s);

3.71 (4 H, m); 4.05 (8 H, br s); 4.34 (8 H, t); 4.83 (8 H, m); 5.46

(2 H, br s); 5.70 (8 H, t, J ) 7.0 Hz); 6.87 (4 H, s); 6.91 (2 H,

s); 6.93 (2 H, s); 7.17 (16 H, m); 7.23 (24 H, m); FAB MS m/ e

(2401.0, M⁺), 2401.1 (100). Anal. Calcd for C₁₅₃H₁₄₈O₂₆: C,

76.48; H, 6.21. Found: C, 76.31; H, 6.05.

8.Na p h th a len e. Application of procedure G to 30 mg

(0.013 mmol) of 8.CHCl₃, 166 mg of naphthalene (1.3 mmol),

and 1.5 mL of Ph₂O gave, after preparative TLC with CHCl₃,

26 mg (84%) of 8.naphthalene: ¹H NMR δ 1.31 (8 H, m);

1.85-2.10 (6 H, m); 2.21 (4 H, br s); 2.55 (16 H, m); 2.71 (16

H, m); 3.15 (4 H, m); 3.21 (4 H, m); 3.36 (4 H, br s); 4.21 (4 H,

br s); 4.21 (4 H, br s); 4.31 (8 H, t, J ) 7.2 Hz); 4.88 (8 H, t, J

) 7.7 Hz); 5.62 (8 H, dd, J ) 7.0 Hz); 6.93 (4 H, s); 7.09 (2 H,

s); 7.11 (2 H, s); 7.17 (16 H, m); 7.24 (24 H, m); FAB MS m/ e

(2391.0, M⁺), 2391.8 (100), 2265.5, (80). Anal. Calcd for

C₁₅₅H₁₄₆O₂₄: C, 77.80; H, 6.15. Found: C, 78.10; H, 6.29.

9.DMSO. Application of procedure E to 100 mg (0.045

mmol) of diol 2, 50 mL of DMSO, 1 g of Cs₂CO₃, and 40 mg

(0.18 mmol) of 2,3-bis(bromomethyl)quinoxaline gave 79 mg

(72%) of 9.DMSO after preparative TLC (CHCl₃): ¹H NMR δ

-0.71 (6 H, s); 2.03 (12 H, m); 2.46 (16 H, m); 2.67 (16 H, m);

3.86 (12 H, m); 4.11 (4 H, d, J ) 7.4 Hz); 4.15 (4 H, d, J ) 7.4

Hz); 4.50 (4 H, t, J ) 7.6 Hz); 4.82 (4 H, t, J ) 7.6 Hz); 5.43 (4

H, s); 5.78 (4 H, d, J ) 7.5 Hz); 5.82 (4 H, d, J ) 7.5 Hz); 6.80

(4 H, s); 6.85 (2 H, s); 6.91 (2 H, s); 7.14 (16 H, m); 7.24 (24 H,

m); 7.79 (2 H, m); 8.13 (2 H, m); FAB MS, m/ e (2427.0, M⁺),

2430.1 (100), 2351.2 (50). Anal. Calcd for C₁₅₂H₁₄₂N₂O₂₅S: C,

75.17; H, 5.89. Found: C, 74.95; H, 6.13.

9.1,4-(MeO)₂C₆H₄. Application of procedure D to 100 mg

(0.045 mmol) of diol 2, 10 mL of HMPA, 1 g of Cs₂CO₃, 620

mg (4.5 mmol) of 1,4-dimethoxybenzene, 20 mg (0.09 mmol)

of 2,3-bis(bromomethyl)quinoxaline, and an additional 20 mg

(0.09 mmol) of 2,3-bis(bromomethyl)quinoxaline (maximum

temperature 50 °C) gave after preparative TLC with CHCl₃

38 mg (34%) of 9.1,4-(MeO)₂C₆H₄: ¹H NMR δ -0.45 (6 H, s);

1.08 (4 H, m); 2.05 (8 H, m); 2.51 (16 H, m); 2.71 (16 H, m);

3.12 (4 H, m); 4.01 (4 H, m); 4.05 (4 H, d, J ) 7.0 Hz); 4.21 (4

H, m); 4.39 (4 H, d, J ) 7.0 Hz); 4.78 (4 H, t, J ) 7.7 Hz); 4.93

(4 H, t, J ) 7.7 Hz); 5.24 (4 H, s); 5.59 (4 H, d, J ) 6.9 Hz);

5.76 (4 H, d, J ) 6.9 Hz); 5.81 (4 H, s); 6.81 (2 H, s); 6.84 (4 H,

s); 6.88 (2 H, s); 7.17 (16 H, m); 7.23 (24 H, m); 7.73 (2 H, m);

7.96 (2 H, m); FAB MS, m/ e (2487.0, M⁺), 2488.9 (100). Anal.

Calcd for C₁₅₈H₁₄₆N₂O₂₆: C, 76.25; H, 5.91. Found: C, 76.07;

H, 6.05.

8.4-MeC₆H₄OMe. Application of procedure G to 30 mg

(0.013 mmol) of 8.CHCl₃and 1 mL of 4-MeC₆H₄OMe gave 29

mg (92%) of 8.4-MeC₆H₄OMe: ¹H NMR δ -1.98 (3 H, s);

-0.28 (3 H, s); 1.63 (8 H, br s); 1.84 (6 H, br s); 2.04 (4 H, br

s); 2.52 (16 H, m); 2.69 (16 H, m); 3.46 (2 H, m); 3.59 (2 H, m);

3.70 (4 H, br s); 4.04 (8 H, br s); 4.14 (2 H, d, J ) 7.0 Hz); 4.16

(2 H, d, J ) 7.0 Hz); 4.22 (2 H, d, J ) 7.0 Hz); 4.29 (2 H, d, J

) 7.0 Hz); 4.88 (8 H, m); 5.69 (2 H, d, J ) 6.9 Hz); 5.71 (2 H,

d, J ) 6.9 Hz); 5.73 (2 H, d, J ) 6.9 Hz); 5.78 (2 H, d, J ) 6.9

Hz,); 5.84 (2 H, d, J ) 8.5 Hz); 5.95 (2 H, d, J ) 8.5 Hz); 6.85

(4 H, d, J ) 8.1 Hz); 6.87 (2 H, d, J ) 4.0 Hz); 6.92 (2 H, d, J

) 4.0 Hz); 7.17 (16 H, m); 7.24 (24 H, m); FAB MS m/ e (2385.0,

61,62,63,64-Tetr a h yd r o-6,14,16,44,46,54,75,84-octa p h en -

eth yl-33H-22,38-(ep oxybu ta n oxy)-8,12:48,52-d im eth a n o-

5,17:28,32:43,55-tr im eth en o-4,18,42,56-(m eth yn oxybu ta n -

oxym e t h yn o)-6H ,14H ,16H ,27H ,42H ,46H ,54H -b is[1,3]-

b e n zod ioxocin o[9,8-d :9′,8′-d ′]b is[1,3]b e n zod ioxocin o-

[9′,10′:4,5;10′′,9′′:12,13][1,3,6,11,14,16,19,27]octaoxacyclon on -

a cosin o[17,18-j:29,28-j′]bis[1,3]ben zod ioxocin , Ster eoiso-

M⁺), 2386.3 (100), 2265.5 (40). Anal. Calcd for C₁₅₃H₁₄₈O₂₅

C, 76.99; H, 6.25. Found: C, 77.16; H, 6.24.

:

9338 J . Org. Chem., Vol. 61, No. 26, 1996

Yoon et al.

m er 10.CHCl₃. Application of procedure E to 100 mg (0.045

mmol) of diol 2, 50 mL of NMP, 1 g of Cs₂CO₃, 16 mg (0.09

mmol) of 1,3-bis(chloromethyl)benzene, and 16 mg (0.09 mmol)

of additional dichloride gave after preparative TLC with

CHCl₃: 88 mg (81%) of 10.CHCl₃: ¹H NMR δ 1.94 (12 H, m);

2.48 (16 H, m); 2.68 (16 H, m); 3.86 (4 H, br s); 3.96 (4 H, br

s); 4.04 (4 H, br s); 4.24 (8 H, t, J ) 7.5 Hz); 4.85 (8 H, t, J )

7.8 Hz); 5.06 (4 H, s); 5.73 (4 H, d, J ) 7.1 Hz); 5.89 (4 H, d,

J ) 7.1 Hz); 6.82 (2 H, s); 6.87 (6 H, s); 7.03 (2 H, d); 7.17 (16

H, m); 7.23 (24 H, m); 7.74 (1 H, s); FAB MS m/ e (2414.9, M⁺)

(2 H, d, J ) 7.0 Hz); 4.22 (2 H, d, J ) 7.0 Hz); 4.29 (2 H, d, J

) 7.0 Hz); 4.89 (8 H, m); 5.62 (4 H, d, J ) 8.4 Hz); 5.62 (4 H,

t, J ) 6.8 Hz); 5.73 (2 H, d, J ) 6.9 Hz); 5.80 (2 H, d, J ) 6.9

Hz); 5.87 (2 H, d, J ) 8.5 Hz); 6.01 (2 H, d, J ) 8.5 Hz); 6.80-

7.01 (8 H, m); 7.17 (16 H, m); 7.24 (24 H, m); 7.38 (1 H, t);

7.80 (1 H, s); FAB MS m/ e (2419.0, M⁺) 2419.9 (100). Anal.

Calcd for C₁₅₆H₁₄₆O₂₅: C, 77.40; H, 6.08. Found: C, 77.71; H,

6.26.

10.1,2,3-(MeO)₃C₆H₃. Application of procedure F to 30 mg

(0.013 mmol) of 10.CHCl₃, 220 mg of 1,2,3-trimethoxybenzene

(1.3 mmol), and 1 mL of Ph₂O gave after preparative TLC with

CHCl₃26 mg (80%) of 10.1,2,3-(MeO)₃C₆H₃: ¹H NMR δ -0.41

(6 H, s); 1.45 (8 H, br s); 2.08 (4 H, br s); 2.51 (16 H, m); 2.71

(16 H, m); 3.05 (3 H, s); 3.62 (8 H, br s); 4.12 (4 H, br s); 4.39

(4 H, d, J ) 7.2 Hz); 4.49 (4 H, d, J ) 7.2 Hz); 4.92 (8 H, m);

5.18 (4 H, s); 5.67 (4 H, d, J ) 6.9 Hz); 5.73 (4 H, d, J ) 6.9

Hz); 6.86 (4 H, s); 6.90 (2 H, s); 6.98 (2 H, s); 7.18 (16 H, m);

7.24 (24 H, m); 7.34 (2 H, d); 7.46 (1 H, t); 7.60 (1 H, s); FAB

MS m/ e (2465.0, M⁺) 2468.3 (100). Anal. Calcd for

C₁₅₇H₁₄₈O₂₇: C, 76.44; H, 6.05. Found: C, 76.26; H, 5.94.

61,62,63,64-Tetr a h yd r o-6,14,16,44,46,54,75,84-octa ph en -

eth yl-33H-22,38-(ep oxybu ta n oxy)-8,12:48,52-d im eth a n o-

5,17:43,55-d im et h en o-4,18,42,56-(m et h yn oxyb u t a n oxy-

m eth yn o)-28,32-n itr ilo-6H,14H,16H,27H,44H,46H,54H-bis-

[1,3]b e n z o d i o x o c i n o [9,8-d :9′,8′-d ′]b i s [1,3]b e n z o d i -

oxocin o[9′,10′:4,5;10′′,9′′:12,13][1,3,6,11,14,16,19,27]octa ox-

a cyclon on a cosin o[17,18-j:29,28-j′]b is[1,3]b e n zod ioxo-

cin , Ster eoisom er 11.CHCl₃. A mixture of 100 mg (0.045

mmol) of diol 2, 50 mL of NMP, 1 g of Cs₂CO₃, and 16 mg (0.09

mmol) of 2,6-bis(chloromethyl)pyridine was stirred at 25 °C

for 5 h, and then the temperature was raised to 50 °C and the

mixture stirred for 24 h. The solution was stirred for another

24 h after the addition of 16 mg (0.09 mmol) of 2,6-bis-

(chloromethyl)pyridine. The solvent was removed in vacuo,

and the residue was dissolved in CHCl₃. The remaining solids

were filtered through a 1 cm pad of Celite, and the filtrate

was rotary evaporated, concentrated to ∼3 mL, and poured

into 100 mL of methanol. The precipitate that formed was

filtered and chromatographed on a preparative TLC plate with

CHCl₃to give 84 mg (77%) of 11.CHCl₃: ¹H NMR δ 1.91 (8

H, m); 1.98 (4 H, m); 2.49 (16 H, m); 2.69 (16 H, m); 3.87 (4 H,

m); 3.90 (4 H, m); 3.98 (4 H, br s); 4.20 (4 H, d); 4.32 (4 H, d);

4.83 (8 H, m); 5.12 (4 H, s); 5.62 (4 H, d, J ) 6.2 Hz); 5.82 (4

H, d, J ) 6.2 Hz); 6.81 (2 H, s); 6.83 (4 H, s); 6.88 (2 H, s); 7.03

(2 H, d); 7.17 (16 H, m); 7.24 (24 H, m); 7.35 (1 H, br s); FAB

MS m/ e (2415.9, M⁺) 2420 (100), 2300 (25). Anal. Calcd for

C₁₄₈H₁₃₆Cl₃NO₂₄: C, 73.48; H, 5.78. Found: C, 73.22; H, 5.57.

11.Na p h th a len e. Application of procedure F to 30 mg

(0.013 mmol) of 11.CHCl₃, 166 mg of naphthalene (1.3 mmol),

and 1.5 mL of Ph₂O gave after preparative TLC with CHCl₃

27 mg (87%) of 11.naphthalene: ¹H NMR δ 1.20 (8 H, m);

2.19 (4 H, m); 2.57 (16 H, m); 2.71 (16 H, m); 3.12 (8 H, m);

3.37 (4 H, m); 4.19 (4 H, br s); 4.20 (4 H, d, J ) 7.0 Hz); 4.30

(4 H, d, J ) 7.0 Hz); 4.87 (8 H, m); 5.38 (4 H, s); 5.53 (4 H, d,

J ) 6.9 Hz); 5.58 (4 H, d, J ) 6.9 Hz); 6.94 (4 H, s); 7.12 (2 H,

s); 7.18 (16 H, m); 7.24 (24 H, m); 7.64 (1 H, t); FAB MS m/ e

(2426.0, M⁺) 2427.9 (100), 2300.5 (80). Anal. Calcd for

C₁₅₇H₁₄₃NO₂₄: C, 77.67; H, 5.94. Found: C, 77.29; H, 5.83.

11.1,2-(MeO)₂C₆H₄. Application of procedure F to 30 mg

(0.013 mmol) of 11.CHCl₃and 1 mL of 1,2-(MeO)₂C₆H₄gave

after preparative TLC with CHCl₃27 mg (84%) of 11.1,2-

(MeO)₂C₆H₄: ¹H NMR δ 1.58 (8 H, br s); 2.05 (4 H, br s); 2.53

(16 H, m); 2.70 (16 H, m); 3.57 (4 H, br s); 3.67 (4 H, m); 4.11

(4 H, br s); 4.25 (8 H, m); 4.87 (8 H, m); 5.27 (4 H, s); 5.55 (2

H, br s); 5.69 (8 H, d, J ) 7.0 Hz); 6.89 (4 H, s); 6.97 (2 H, s);

6.98 (2 H, s); 7.18 (16 H, m); 7.24 (24 H, m); 7.34 (2 H, d); 7.59

(1 H, br s); FAB MS m/ e (2436.0, M⁺) 2438.6 (100), 2300.9

2419 (40), 2299 (100). Anal. Calcd for C₁₄₉H₁₃₇Cl₃O₂₄

74.01; H, 5.71. Found: C, 73.76; H, 5.78.

: C,

10.CHCl₂CHCl₂. Application of procedure B to 30 mg

(0.013 mmol) of 10.CHCl₃and 1 mL of tetrachloroethane gave

after preparative TLC with CHCl₃29 mg (91%) of 10.CH-

Cl₂CHCl₂: ¹H NMR δ 1.93 (12 H, m); 2.51 (16 H, m); 2.69 (16

H, m); 3.87 (4 H, br s); 3.97 (4 H, br s); 4.03 (4 H, br s); 4.35

(2 H, s); 4.38 (8 H, t, J ) 7.5 Hz); 4.84 (8 H, t, J ) 7.8 Hz);

5.04 (4 H, s); 5.69 (4 H, d, J ) 7.0 Hz); 5.84 (4 H, d, J ) 7.0

Hz); 6.83 (2 H, s); 6.86 (6 H, s); 7.05 (2 H, d, J ) 7.3 Hz); 7.17

(16 H, m); 7.23 (24 H, m); 7.73 (1 H, s); FAB MS m/ e (2462.8,

M⁺), 2466 (100), 2298 (90). Anal. Calcd for C₁₅₀H₁₃₈Cl₄O₂₄

C, 73.04; H, 5.64. Found: C, 73.36; H, 5.38.

:

10.1,4-(MeO)₂C₆H₄. Application of procedure G to 30 mg

(0.013 mmol) of 10.CHCl₃, 180 mg of 1,4-dimethoxybenzene

(1.3 mmol), and 1 mL of Ph₂O gave 28 mg (90%) of 10.1,4-

(MeO)₂C₆H₄: ¹H NMR δ -0.38 (6 H, s); 1.49 (8 H, br s); 2.05

(4 H, br s); 2.53 (16 H, m); 2.71 (16 H, m); 3.55 (4 H, br s);

3.58 (4 H, br s); 4.09 (4 H, br s); 4.25 (4 H, d, J ) 7.0 Hz); 4.27

(4 H, d, J ) 7.0 Hz); 4.91 (8 H, t); 5.10 (4 H, s); 5.68 (4 H, d,

J ) 6.9 Hz); 5.73 (4 H, d, J ) 6.9 Hz); 5.84 (4 H, s); 6.84 (4 H,

s); 6.88 (2 H, s); 6.91 (2 H, s); 7.19 (16 H, m); 7.24 (24 H, m);

7.32 (2 H, d, J ) 7.6 Hz); 7.69 (1 H, s); FAB MS m/ e (2435.0,

M⁺) 2435 (100). Anal. Calcd for C₁₅₆H₁₄₆O₂₆: C, 76.89; H, 6.04.

Found: C, 76.98; H, 6.00.

10.1,3-(MeO)₂C₆H₄. Application of procedure F to 30 mg

(0.013 mmol) of 10.CHCl₃and 1 mL of 1,3-dimethoxybenzene

gave after preparative TLC with CHCl₃, 27 mg (89%) of

10.1,3-(MeO)₂C₆H₄: ¹H NMR δ -0.53 (6 H, s); 1.45 (8 H, br

s); 2.05 (4 H, br s); 2.53 (16 H); 2.72 (16 H, m); 3.49 (4 H, br s);

3.55 (4 H, br s); 4.08 (4 H, br s); 4.29 (8 H, d, J ) 6.8 Hz); 4.91

(8 H, t); 5.03 (2 H, d); 5.13 (4 H, s); 5.48 (1 H, s); 5.66 (4 H, d,

J ) 7.0 Hz); 5.73 (4 H, d, J ) 6.9 Hz); 6.83 (4 H, s); 6.89 (2 H,

s); 6.93 (2 H, s); 7.19 (16 H, m); 7.24 (24 H, m); 7.43 (1 H, t);

7.78 (1 H, s); FAB MS m/ e (2435.0, M⁺) 2436 (100). Anal.

Calcd for C₁₅₆H₁₄₆O₂₆: C, 76.89; H, 6.04. Found: C, 76.66; H,

6.23.

10.1,2-(MeO)₂C₆H₄. Application of procedure F to 30 mg

(0.013 mmol) of 10.CHCl₃and 1 mL of 1,2-(MeO)₂C₆H₄gave

after preparative TLC with CHCl₃, 27 mg (87%) of 10.1,2-

(MeO)₂C₆H₄: ¹H NMR δ 1.59 (8 H, br s); 2.03 (4 H, br s); 2.50

(16 H, m); 2.68 (16 H, m); 3.58 (4 H, br s); 3.69 (4 H, m); 4.08

(4 H, br s); 4.30 (8 H, t, J ) 7.5 Hz); 4.88 (8 H, m); 5.12 (4 H,

s); 5.45 (2 H, br s); 5.71 (8 H, d, J ) 7.8 Hz); 6.89 (4 H, s); 6.99

(2 H, s); 7.01 (2 H, s); 7.18 (16 H, m); 7.24 (24 H, m); 7.34 (2

H, d); 7.51 (1 H, t); 7.71 (1 H, s); FAB MS m/ e (2435.0, M⁺)

2436 (100). Anal. Calcd for C₁₅₆H₁₄₆O₂₆: C, 76.89; H, 6.04.

Found: C, 76.62; H, 6.09.

10.Na p h th a len e. Application of procedure G to 30 mg

(0.013 mmol) of 10.CHCl₃, 166 mg of naphthalene (1.3 mmol),

and 1.5 mL of Ph₂O gave after preparative TLC with CHCl₃

27 mg (85%) of 10.naphthalene: ¹H NMR δ 1.31 (8 H, m);

2.20 (4 H, m); 2.56 (16 H, m); 2.71 (16 H, m); 3.12 (4 H, m);

3.21 (4 H, m); 3.35 (4 H, m); 4.19 (4 H, br s); 4.30 (4 H, d, J )

7.1 Hz); 4.34 (4 H, d, J ) 7.1 Hz); 4.89 (8 H, m); 5.21 (4 H, s);

5.54 (4 H, d, J ) 6.9 Hz); 5.61 (4 H, d, J ) 6.9 Hz); 6.98 (4 H,

s); 7.12 (2 H, s); 7.18 (16 H, m); 7.24 (24 H, m); 7.41 (1 H, t);

8.08 (1 H, s); FAB MS m/ e (2425.0, M⁺) 2425.1 (100). Anal.

Calcd for C₁₅₈H₁₄₄O₂₄‚2H₂O: C, 77.05; H, 6.06. Found: C,

77.04; H, 5.95.

(30). Anal. Calcd for C₁₅₅H₁₄₅NO₂₆

Found: C, 76.53; H, 5.99.

: C, 76.37; H, 6.00.

11.1,3-(MeO)₂C₆H₄. Application of procedure F to 30 mg

(0.013 mmol) of 11.CHCl₃and 1 mL of 1,3-dimethoxybenzene

gave after preparative TLC with CHCl₃, 27 mg (86%) of

11.1,3-(MeO)₂C₆H₄: ¹H NMR δ -0.50 (6 H, s); 1.40 (8 H, m);

2.08 (4 H, br s); 2.52 (16 H, m); 2.71 (16 H, m); 3.53 (8 H, m);

4.11 (4 H, br s); 4.35 (8 H, d, J ) 6.8 Hz); 4.90 (8 H, t); 5.00 (2

H, d); 5.34 (4 H, s); 5.49 (1 H, s); 5.70 (8 H, d, J ) 7.0 Hz);

10.4-MeC₆H₄OMe. Application of procedure F to 30 mg

(0.013 mmol) of 10.CHCl₃and 1 mL of 4-MeC₆H₄OMe gave

28 mg (90%) of 10.4-MeC₆H₄OMe: ¹H NMR δ -1.96 (3 H, s);

-0.26 (3 H, s); 1.58 (8 H, br s); 2.03 (4 H, br s); 2.50 (16 H, m);

2.69 (16 H, m); 3.39 (2 H, m); 3.58 (2 H, m); 3.62 (2 H, m);

3.71 (2 H, m); 4.02 (4 H, br s); 4.16 (2 H, d, J ) 7.0 Hz); 4.18

Seven New Hemicarcerands

J . Org. Chem., Vol. 61, No. 26, 1996 9339

6.83 (4 H, s); 6.89 (2 H, s); 6.93 (2 H, s); 7.19 (16 H, m); 7.24

(24 H, m); 7.74 (1 H, br s); FAB MS m/ e (2436.0, M⁺) 2437.9

(90), 2300.4 (100). Anal. Calcd for C₁₅₅H₁₄₅NO₂₆: C, 76.37;

H, 6.00. Found: C, 76.40; H, 5.98.

11.4-MeC₆H₄OMe. Application of procedure F to 30 mg

(0.013 mmol) of 11.CHCl₃and 1 mL of 4-MeC₆H₄OMe gave

28 mg (90%) of 11.4-MeC₆H₄OMe: ¹H NMR δ -1.98 (3 H, s,

guest CH₃); -0.29 (3 H, s); 1.58 (8 H, br s); 2.02 (4 H, br s);

2.50 (16 H, m); 2.69 (16 H, m); 3.38 (2 H, m); 3.54 (2 H, m);

3.61 (2 H, m); 3.68 (2 H, m); 4.02 (4 H, br s); 4.15 (8 H, m);

4.87 (8 H, m); 5.48 (4 H, d); 5.72 (8 H, m); 5.78 (2 H, d); 5.90

(2 H, d); 6.80-7.01 (8 H, m); 7.17 (16 H, m); 7.24 (24 H, m);

7.71 (1 H, m); FAB MS m/ e (2420.0, M⁺) 2421.2 (100), 2300.7

hemicarceplexes were dissolved in 0.5 mL of CDCl₃at 25 °C,

and changes in guest-proton spectra were monitored over the

periods indicated in Table 3. The half-lives for decomplexation

were calculated from the first-order rate constants for either

disappearance of complexed guest and/or appearance of free

guest.

Su p p or tin g In for m a tion Ava ila ble: Details of crystal-

lographic data collection and refinement for 8.4-MeC₆H₄-

.

OMe∪2C₆H₅NO₂and 10.CHCl₃∪2C₆H₅NO₂2C₆H₅NO₂(2

3

pages). This material is contained in libraries on microfiche,

immediately follows this article in the microfilm version of the

journal, and can be ordered from the ACS; see any current

masthead page for ordering information.

(30). Anal. Calcd for C₁₅₅H₁₄₅NO₂₅

Found: C, 77.13; H, 6.00.

: C, 76.87; H, 6.03.

Kin etics of Decom p lexa tion s of 7.gu est, 8.gu est, a n d

10.gu est in CDCl₃. Solutions of 5-7 mg of the three

J O9612786

Article Doi

Syntheses, binding properties, and structures of seven new hemicarcerands each composed of two bowls bridged by three tetramethylenedioxy groups and a fourth unique linkage

DOI: 10.1021/jo9612786

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Article abstract of DOI:10.1021/jo9612786

Full text of DOI:10.1021/jo9612786

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