§§> \IHHIWINIIWIHHIHINWWUIWHIIWIHHII

”THS

     

7115348

\
QOOl

 

LIBRARY
Michigan State
University

--——-— ‘ai

 

 

This is to certify that the
thesis entitled
Photochemistry of
beta-Cyclopropylmethoxypropiophenone
and O-Benzyl Benzophenone

presented by

Varsha S. Govardhan

has been accepted towards fulfillment
of the requirements for

M. S . _degree in Cheml Stf‘y

WE‘W

 

Date a? 93; (9590/

0-7639 MS U is an Affirmative Action/Equal Opportunity Institution

 

PLACE IN RETURN Box to remove this checkout from your record.
TO AVOID FINES return on or before date due.
MAY BE RECALLED with earlier due date if requested.

 

DATE DUE

DATE DUE

DATE DUE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

6/01 c:/cmcroatooue.pes-p.15

 

 

PHOTOCHEMISTRY OF B-CYCLOPROPYLMETHOXY PROPIOPHENONE AND
O-BENZYL BENZOPHENONE

By

Varsha S. Govardhan

A THESIS

Submitted to
Michigan State University
in partial fulfillment of the requirements
for the degree of

MASTER OF SCIENCE
Department of Chemistry

2001

ABSTRACT

PHOTOCHEMISTRY OF B-CYCLOPROPYLMETHOXY PROPIOPHENONE AND
O-BENZYL BENZOPHENONE

By

Varsha S. Govardhan

Intramolecular hydrogen abstraction is one of the major outcomes of irradiating
carbonyl compounds which have a molecular structure that allows a close approach
between the excited carbonyl compound and a sp3 carbon within the same molecule.
This process is favored fi'om the 7 carbon due to geometric and thermodynamic
considerations. However abstraction from the 5 carbon is a competing reaction that can

occur with highly activated 5 C—H bonds or in the absence of y hydrogens.

B-Cyclopropylmethoxy propiophenone proved to be an interesting example of the
latter. In this case 1,5 biradical formation was followed by subsequent radical ring
opening of the cyclopropyl moiety as opposed to cyclopentanol formation seen with other
compounds such as B-ethoxypropiophenone.

Photoenolization followed by electrocyclic ring closure to stereoselectively form
the cyclobutenol was the result of irradiating o-benzyl benzophenone, which was a
classic example of photoenolization. To reinforce our understanding of the
ketone—éenol—)benzocyclobuteno ls chronology, this process was also studied in the solid
state. The difference in the diastereoselectivity of cyclobutenol formation between the
solid and liquid state confirms the fact that it is governed by the geometry of the biradical

initially formed by hydrogen abstraction.

AKNOWLEDGEMEN TS

I wish to thank Dr. Peter J. Wagner, for his help, guidance along with moral and
financial support. His help through rough times led to the completion of this thesis.

I am also greatly indebted to members of the Wagner group, Dr. Yoon, Mr. Jong'
11 Lee, Mr. Yijun Tang, Dr. Ali land and Prof. Bong-Ser Park for their help and
discussions throughout my graduate career and making it fun to work in the laboratory. I
owe special thanks to Dr. Azadnia who worked with my schedule during my pregnancy.

Finally I would like to thank my husband Dr. Subodh Govardhan whose love and
patience has always been a source of inspiration, my parents, Mr. Manohar and Mrs.
Manisha Bhide, my parents-in-law, Dr. Manohar and Mrs. Lata Goverdhan, my brother

Mr. Vivek Bhide and last but by all means one of the most important, my daughter Ms.

Isheeta Govardhan.

000

TABLE OF CONTENT

INTRODUCTION ......................................................................................................... 1
Hydrogen abstraction ....................................................................................................... 2
Singlet vs triplet excited state ......................................................................................... 4
Orientational requirements for intramolecular hydrogen transfer ..................................... 5
Biradical lifetimes ........................................................................................................... 6
More remote hydrogen abstraction ................................................................................ 12
Photoenolization ............................................................................................................ 13
Quantum yields and quenching studies .......................................................................... 15
Goals of research ........................................................................................................... 16
RESULTS AND DISCUSSION .................................................................................. 18
Irradiation of B-cyclopropylmethoxypropiophenone (CMP) .......................................... 18
Quantum yield ............................................................................................................... 22
Quenching study ............................................................................................................ 23
Photochemistry of o-benzyl benzophenone .................................................................... 25
EXPERIMENTAL ........................................................ Error! Bookmark not defined.
General procedures ........................................................................................................ 31
Photochemistry of CMP ................................................................................................ 39
Quantum yield ............................................................................................................... 41
Quenching studies ......................................................................................................... 43
Photochemistry of BZBP ............................................................................................... ' 44
REFERENCES ............................................................................................................ 47

iv

LIST OF SCHEMES

Scheme 1. Norrish type II reactions ................................................................................ 2
Scheme 2. Competition between oc-cleavage and hydrogen abstraction ........................... 3
Scheme 3. Photoproducts from the irradiation of 8-methoxy valerophenone ................. 12
Scheme 4. Photochemistry of o-alkyl phenyl ketones26a ................................................ 14
Scheme 5. Synthesis of CMP ........................................................................................ 32
Scheme 6. Synthesis of BZBP ...................................................................................... 35

LIST OF FIGURES

Figure l. Jablonski diagram ............................................................................................ 1
Figure 2. Chair like transition state for hydrogen abstraction .......................................... 3
Figure 3. Reaction of singlet and triplet n,1t* states with C-H bonds ............................... 4
Figure 4. Orientational parameters for hydrogen abstraction ........................................... 5
Figure 5. Life time of 1,4 biradical containing oxygen .................................................... 7
Figure 6. Conformational effect in photochemistry of o-tett-butylbenzophenone ............ 8
Figure 7. Different behavior of oCPB and oCPA biradicals ............................................ 9
Figure 8. Products from photochemistry of B-ethoxy propiophenone ............................ 10
Figure 9. Photoenolization of 2-a1kyl phenyl ketones .................................................... 13
Figure 10. lH-NMR of compound A .............................................................................. 19
Figure 11. lH-NMR of compound B .............................................................................. 20
Figure 12. Structure of compound A ............................................................................. 21
Figure 13. Structure of compound B ............................................................................. 21
Figure 14. Pr0posed mechanism for product formation ................................................. 22
Figure 15. Stem Volmer quenching results for compound A ......................................... 24
Figure 16. Stem Volmer quenching results for compound B ......................................... 24
Figure 17. Photochemistry of BZBP ............................................................................. 26
Figure 18. lH-NMR for BZBP in toluene-d6 Before (A) and After (B) irradiation ....... 27
Figure 19. Irradiation of solid BZBP ............................................................................. 28
Figure 20. Formation of the four o-xylylenols and benzocyclobutenols ......................... 29
Figure 21. l3C-NMR of B—cyclopropylmethoxypropiophenone ...................................... 34
Figure 22. Hetero-COSY spectrum of CMP .................................................................. 35
Figure 23. Photochemistry of CMP ............................................................................... 39

INTRODUCTION

Chemical reactions can broadly be classified into two categories — thermal and
photochemical.

When the source of energy in a reaction is light, it is termed as a photoreaction.
For a photoreaction to occur, a molecule in its ground state, So, absorbs light and is
excited to Sn, the singlet excited state. From here the excited molecule can intersystem

cross, i.e. go to the triplet excited state Tn with a rate constant of 107 —1011 s".1

   

    

Products Products

S0 SI T1
.A = absorption IC = internal conversion
F = fluorescence ISC = intersystem conversion
P = phosphorescence VR = vibrational relaxation

Figure 1. Jablonski diagram

Photophysical processes like radiative decay (phosphorescence), radiationless
decay, or photochemical transformations like hydrogen abstraction, a-cleavage etc. can

occur from T1. The molecule from S1‘ can also undergo internal conversion to the lowest

excited singlet state, S. with a rate of the order of lO”-10l2 s". This singlet state can

decay to the ground state by emitting light, giving rise to fluorescence. Chemical

reactions are possible from this state also.

Hydrogen Abstraction

Hydrogen abstraction can occur both inter- and intramolecularly. Intramolecular
hydrogen abstraction and the fate of the resulting biradical is the focus of this study. The
(n,1t*) excited state of carbonyl compounds undergoes a 1,5 or 1,6-hydrogen shift, which
is generally followed by cyclization, cleavage, or reversal to the starting ketone.2 As in
most chemical reactions various steric, electronic and physical factors affect the

feasibility and rate of hydrogen abstraction and fate of the resulting biradical.

OH
1R2

\ / 1'“!
MC — R1 < > MC — R1
reverse
R H transfer R
flavagNlizati on

0 OH R; OH R2

+
<—— ,g R R
R 1
RJLCH3 R CH2 HZC&\1 I |

 

 

Scheme 1. Norrish type 11 reactions

Ketones, aldehydes, esters and cyclic imides, in which the molecular structure

allows a close approach between the excited carbonyl group and hydrogen attached to a

V
I

 

OH °~

 

Figure 2. Chair like transition state for hydrogen abstraction

sp3 hybridized carbon within the same molecule, undergo intramolecular abstraction.
This process is favored at the 7 carbon due to geometrical and thermodynamic

considerations.

Hydrogen abstraction

O ——' “<33.

 

(b: 1.033
ot-cleavage
H C CH3
oH3C O , OH
0 Ph
H3C CH3
0:0.03"
H O
O 0 “
k CH3 CH3 j
e 0.383c

Scheme 2. Competition between ot-cleavage and hydrogen abstraction

1n the absence of y hydrogen or when the molecular conformation allows other
sites to come in close proximity to the excited carbonyl group the hydrogen shifi can
occur from other positions as well. Hydrogen abstraction can occur from both the singlet
and triplet states. though in aromatic ketones it typically occurs from the triplet state.
giving rise to a triplet biradical. If hydrogen abstraction is slowed down. (Jr-cleavage
reactions can compete.” 3° These are also called as Norrish Type I reactions and can

occur due to a high degree of steric crowding in the reacting ketone.

Singlet vs triplet excited state

MINDO calculations performed by Dewar “ on butyraldehyde supported the idea
that triplet reactions occur extensively via biradicals and singlet reactions promote direct

radiationless decay and may form products in a concerted fashion.

 

GS

OH

1 H-CR; A 'CRa

Figure 3. Reaction of singlet and triplet n,1r* states with C-H bonds

It is now very easy to detennine whether the reaction is singlet or triplet derived,
using flash kinetics9 or trapping studies.4b Photoreactions from aliphatic ketones involve
both singlets and triplets,3a but in most phenyl ketones the rapid rate of intersystem

crossing promotes exclusive triplet reactivity in bimolecular reactions.3d

Orientational requirements for intramolecular hydrogen transfer

In 1968 Turro suggested that the hydrogen atom to be abstracted should lie along
the long axis of the carbonyl n orbital.5 However later examples showed that hydrogen
transfer took place with the H-0 bond making a fairly large angle with respect to the

nodal plane of the carbonyl 1: system.7

x5.

I

0|) 9 W9“

A I x ' a)
d < 2.7A° o) = 0° A = 90-120° 9 = 180°
Figure 4. Orientational parameters for hydrogen abstraction
Scheffer studied various Type 11 reactions in crystalline state wherein the
geometry was measured by x—ray diffraction.6 He concluded that the parameters that

affect abstraction are d — the distance between H and O, 0 the O-H-C angle, A the C=O~H

angle and a), the dihedral angle that the 0-H vector makes with respect to the nodal plane

of the carbonyl 1: system. For the several ketones he studied, the values of d ranged from

2.3 — 3.1 A°, 0 from 85 - 120°, A from 74 - 103° and (o from O - 62°. In. the present

research one of the compounds, B-cyclopropylmethoxypropiophenone has no
orientational constraints, but the population of the molecules in the right geometry for
abstraction could be very low due to other lower energy conformations. Secondly it was
also proposed that the torsional strain present in the cycloheptane like transition state for
1,6-hydrogen transfers may be responsible for the slower rate of 5-hydrogen abstraction

in straight chain systems.8

Biradical Lifetimes

It is now a well established fact that most of the Type 11 reactions are biradical in
nature. Quantum yields for phenyl ketones reach unity in 2-3 M tert-butyl alcohol, but
even in alcohols, aliphatic triplets do not attain 100% efficiency, leading to the inference
that phenyl biradicals are longer lived than the aliphatic biradicals.“

In 1977, Sciano and Small reported the first flash spectroscopic detection of the
1,4-biradical intermediate from y-methylvalerophenone which has a 30 ns lifetime in
benzene.9 Solvents have a pronounced effect on the lifetime of hydroxy biradicals, which
is considerably increased, presumably due to hydrogen bonding.ls There is a similar
parallel between solvent effects on lifetimes of some 1,5 biradicals.”

Nishida and co-workerslo studied the photoreaction of arylketones with
vinylcyclopropane and have estimated the lifetimes of the 1,4 biradical intermediates
from the product ratios and the cyclopropylethyl rearrangement rate of 2 x 107 s". This

reinforces the fact that oxygen-containing Norrish type II 1,4 biradicals have a short

lifetime.ll Similarly the 1,5 biradicals formed by intramolecular S-hydrogen abstraction

in o-alkoxy ketones also have a very short lifetime.17

R2
0 hv O O O \
)L —-—r p.14" “’Pn *ph
Ph R1 R2 R1 R2 R1 R2
? <| R1

A B C
Product Ratio (B/C) Lifetime of A
RI=H, R2 =H 14.6 4 ns at 50°C
R.=H, R2=CH3 21.0 2.3 us at 75°C
R,=Ph, R2=CH3 4.3 11 ns at 75°C

Figure 5. Life time of 1,4 biradical containing oxygen

6 - Hydrogen abstraction and fate of the consequent biradical
As noted earlier, intramolecular hydrogen abstraction can occur from sites other

than the 7 position, either when there is no y hydrogen or when the molecule provides

effective competition in the formation of a 7-atom cyclic transition state.

An ideal example of the latter is 8-methoxyvalerophenone,l3 in which the
activation of the 6 site is so great that abstraction from this position has the same rate
coeflicient (2.5 x 107 s-1) as that from the 7 position. At the same time it is also true, that
for equivalent C-H bonds, the 8-H abstraction rate is usually only about 5% of that from
the 1 position.8 The species produced from the 6-hydrogen abstraction is a 1,5 diradical,

which cannot undergo simple cleavage like the corresponding 1,4 diradical,” but the

cyclization reaction may occur. A hydrogen-deuterium exchange that occurs between the

a and 8 positions shows that the efficiency of cyclization may be low due to the
disproportionation (hydrogen transfer) to yield the enol of the starting ketone.” The
Wagner group has studied 8-H abstraction for some acyclic compounds as well as some
ortho-substituted phenyl ketones that impose a form of endocyclic restriction on the
photochemistry. Most of the work in this area has been done on aromatic ketones and as
with all such systems the hydrogen abstraction results from the triplet (n, 1t*) state.

The system that is very well studied by the Wagner group, is the ortho—substituted

phenyl ketones.

H3c\g'110H3 5 magma, 0..
“ ——» “
H3C\gH3

.OH
Ph

Figure 6. Conformational effect in photochemistry of o-tert-butylbenzophenone

Among the most cited examples is the ortho-tert-butylbenzophenone, which

undergoes a very clean photoreaction not only in solution but also in the crystalline

state.'6

Hydrogen abstraction occurs with a rate constant >109 3“. X-ray analysis
indicates that the o-t-butylphenyl ring is twisted 69° with respect to the nearly planar
benzoyl group. Two hydrogens on the t-butyl group lie within 2.7 A° of the carbonyl

oxygen, one with an angle a) of 40°, the other with nearly 90°. The former makes a

perfect conformation for hydrogen abstraction, and the rapid kinetics is proof of this.
Various other systems have been studied, with substitutions on the benzene ring or ortho

alkoxy substitution instead of the tert-butyl.

 

Al :7%allZ A2: 13% A3:80%

Figure 7. Different behavior of oCPB and oCPA biradicals

One of the more interesting examples in context with the present research is the
photochemistry of o-(cyclopropylmethoxy) benzophenone (oCPB) and o-
(cyclopropylmethoxy) acetophenone (oCPA),l7 which form different products, the oCPB
cyclizing mainly to the epimeric benzfuranols and the oCPA also forming some
benzfuranol but the major product being the hemiketal of an o-acetylbenzyl alcohol. In

Spite of this difference, both have similar short biradical lifetimes.

Acyclic ,B-alkoxy ketones

Two types of compounds that were extensively studied were, one in which there
was no y-hydrogen and the other where the 5 OH bond was activated by an alkoxy
group.

In 1979 Wagner and Chiu thoroughly investigated the photochemistry of B-
ethoxypropiophenone in order to characterize the formation and behavior of its 1,5
biradical.188 The triplet lifetime of the compound, which presumably is the rate of 5 -

hydrogen abstraction by its lowest n,1t* state, is 2 x 107 s'l which is large enough that no

physical decay competes.

X
( V
O O OH O

é / V *7)
\

OH
16% 35%
Ph °
x x
HO Ph
sz \‘ + ‘
Ph“ 0 HO“ 0
40% 9%

Figure 8. Products from photochemistry of B-ethoxy propiophenone

Its only photoproducts are the two diastereomeric oxacyclopentanols and the enol of the

Starting ketone.

l0

 

 

< hv HO Ph
0 O ————> \‘. \\
M ”‘60 +40de
Ph

X X

X = H benzene 0.40 0.09
t-BuOH OJ 3 0. l 6

X = D benzene 0.52 0.12
t-BuOH 0.23 0.31

 

 

 

Table 1. Quantum Yields for product formation from B-ethoxypropiophenone

The Z/E product ratio depends on solvent polarity. There is little selectivity in
Lewis base solvents, but solvents like benzene strongly favor the isomer with the methyl
trans to the phenyl. Alcohols do not raise the cyclization quantum efficiency, as they do
in the 1,4 biradicals, in which hydrogen bonding to the hydroxy group increases the
effective bulk and supresses the disproportionation back to the starting ketone. In 1,5
biradicals also there is hydrogen bonding, which increases the bulk thus lowering the
distereoselectivity.

In 8-methoxyvalerophenone the rate of 8 hydrogen abstraction is nearly equal to
that from the 7 position.13 However, it is worth noting that the quantum efficiency of
cyclopentanol formation is only 10%. It can thus be concluded that there are other

reactions that compete very well with cyclization of 1,5 biradicals.

ll

ocn3

 

0 hv A
Ph t-BuOH
o H3CO H3CO OCH3 QCH3
,JL, HO Ph “0 ‘ H0 . i‘
P“ CH3 pn\ Ho\“ th “D
o == 037 006 003 0015 0085

Scheme 3. Photoproducts from the irradiation of 5-methoxy valerophenone

More remote hydrogen abstraction

There have been several examples of more remote hydrogen abstraction, ranging
from 8 hydrogen for ketones that have no y or 6 hydrogens19a to cyclization of

benzophenones with long alkyl chains attached at the para position.19b This would make

a very interesting but a whole different field of research.

12

Photoenolization

The photoreduction of benzophenone to benzopinacol is an extensively examined
reaction, which led to the discovery of photoenols in ortho-alkyl phenyl ketones. The
reduction process was shown to proceed by abstraction of hydrogen by the triplet (n,7t*)
state of the carbonyl group. In propan-Z-ol the quantum yield for pinacol formation (bred
is 2.0.20 Introduction of an ortho alkyl substituent having a benzylic hydrogen largely
suppressed the pinacol formation. O-Methylbenzophenone has a quantum yield for
reduction (bred = 5% in propan-2-ol.21 On the other hand, 4-methyl benzophenone gave
high quantum yields of om, = ca.50%.2| These experiments suggested that the reduction

was not being suppressed by electronic factors and thus a photoenol intermediate was

proposed.22

2 OH
O hv / Z
-----> -----> products
\ R
CHRR,
R1
photoenol

Figure 9. Photoenolization of 2-alkyl phenyl ketones

In 1961 Yang and Rivas demonstrated that dienol intermediates obtained by
irradiation of 2-methyl and 2-benzylbenzophenones were sufficiently long lived to allow
chemical trapping, by cycloaddition with a dienophile or quenching with oxygen. These
trapping experiments facilitated a better understanding of the mechanism for

23

photoenolization. The stereoselective nature of cycloaddition products obtained from

the irradiation of 2-methyl-benzophenone in the presence of maleic or fumaric acid also

13

indicates the formation of ground state enols. The term photoenol is no longer unique
due to various other forms of photoenolization and thus the term o-xylylenols has been

26a

suggested by the Wagner group. While chemical trapping was indirect evidence of the

o-xylylenols, transient absorption spectroscopy provided direct evidence of the enol
intermediates. It was not until a decade later that Matsurra reported the subsequent
electrocyclic ring closure of photochemically generated dienols to benzocyclobutenols in
2,4,6-trialkyl phenyl ketones.24 Earlier it was assumed that cyclization occurred only in
sterically congested dienols. However this was not consistent with some of the other
compounds that cyclized. 2-Methylbenzaldehyde on irradiation gives the
benzocylobutenol.25 Upon heating the benzocyclobutenols open to the E-enol with

subsequent reversion to the parent ketone.

 

 

 

 

 

Scheme 4. Photochemistry of o-alkyl phenyl ketonesz“

Scheme 4 depicts the current consensus as to the structure and chronology of the

transient intermediates formed from the triplet o-alkylphenyl ketones.26a Hydrogen

abstraction is followed by a biradical triplet o-xylylenol which decays to the ground state
with both the E and Z configuration of the OH group. The Z configuration is very short
lived and reverts to the starting ketone rapidly, thus all the product formation occurs from
the E isomer. It undergoes acid—base catalyzed reketonization with benzylic H/D
exchange, but is invariably long lived enough to undergo benzocyclobutenol formation,
Diels Alder cycloadditons, dihydroanthrol formation and dimerization. From extensive
research it was concluded that the product geometries and isomer distribution are set

when the biradical triplet xylylenol decays to ground state.26b

Quantum yields and Quenching studies

Quantum Yield of a reaction is the number of molecules of product formed per
photon of light absorbed. The number of photons of light absorbed are usually obtained
with the help of actinometers, which are compounds with known quantum efficiencies.

The Stern-Volmer equation is a mathematical relationship between quantum

yields in the absence (¢°) and presence (4)) of quencher and is written as

W4) = 1 + kqI [Q]
Equation I
A plot of ¢°/¢ versus [Q] should give a straight line with an intercept of 1 and a slope of
kqt. For most cases the quenching is diffusion controlled and thus if kq is known (e.g. it

is 6 x 109 M' s'l in benzene at room temperature), the triplet lifetime can be calculated

from the slope of the Stem-Vohner plot.

Goals of research

Hydrogen abstraction reactions from the 5 carbon have been studied for many
classes of carbonyl compounds. The photochemistry of y-cyclopropylbutyrophenone has
revealed that the 1,4 biradical generated by y-hydrogen abstraction undergoes radical
rearrangements in competition with more normal type II reactions,18b in proportions that
indicate that the lifetime of the biradical is between 35-50 us in benzene. Besides
acetophenone, l-phenyl-4-cycloheptenol and l-phenyl-4-hepten-1-one were identified as
the other major photoproducts. The latter was obtained in a quantum yield of 0.26 in
benzene as solvent, (cis/trans ratio not determined). Thus the question was asked: how
will the addition of an oxygen in the tether effect the biradical lifetime and the outcome
in terms of the products formed? Firstly by putting an oxygen in the chain, we will be
forming a 1,5 biradical (by 5-hydrogen abstraction) and it would be interesting to know
how it would differ in lifetime fiom the preceding 1,4 biradical. Secondly as mentioned
earlier, oxygen is said to have an effect on the 1,4 biradical, wherein the eclipsing effect
is reduced when the carbon atom is replaced with oxygen, which facilitates bringing the
two ends of the biradical together. Another explanation offered for this effect is the spin-
orbit coupling which induces intersystem crossing, probably by through-space interaction

18c

of the unpaired electrons of oxygen. This phenomenon has also been used to explain

the high cyclization efliciency of the or-alkoxyacetophenones.18d

Wagner and Jang” have
also used the radical clock method for determining the biradical lifetimes of o-
(cyclopropylmethoxy)benzophenone and o-(cyclopropylmethoxy)acetophenone, which

are between 2 and 5 ns. The short lifetimes can be attributed to the ease of cyclization

due to two factors, presence of oxygen and rigidity of the molecule. We designed a new

16

molecule, B-(cyclopropylmethoxy)propiophenone keeping in mind the above two as
models. It would be interesting to study how oxygen affects the biradical lifetime for this
molecule. Identification of the photoproducts and their yields reveal the lifetime of the
1,5 biradical formed from 8-hydrogen abstraction. In this case the competing cyclization
and cyclopropylcarbinyl-to—allylcarbinyl rearrangement of the 1,5 biradical will be
studied.

Solution photoenolization of o-benzyl ben20phenone and cyclization of the
o-xylylenols have been studied.26a The outcome in the solid state would help answer
some of the conformational effects on the lifetime on the resulting biradical. Thus these

became the two target molecules of the present research.

17

RESULTS AND DISCUSSION

Irradiation of B-cyclopropylmethoxypropiophenone (CMP)

The ultraviolet absorption spectrum of B-cyclopropylmethoxypropiophenone was
first taken and 313 nm was the wavelength chosen for irradiation. 0.05 M solutions of
the compound in both benzene-d6 and acetonitrile-d; were then irradiated at 313 nm at
room temperature.

The reaction was first followed by lH—NMR, at time intervals of 10
minutes for the first 30 minutes followed by 30 minute intervals. The time intervals were
subsequently increased and the reaction monitored for 24 hours. IH-NMR spectra
indicated the formation of more than one compound, but did not show any one in a
substantially higher yield than other. The reaction was then followed by HPLC, using a
silica column and 97 : 3 mixture of hexane and ethyl acetate. HPLC showed formation of
two distinct compounds with similar absorption patterns, whose peak intensities
increased for the first 24 hours. After 24 hours there was an appearance of the third peak,
with a subsequent increase in its formation while the peak size of the first two
compounds diminished. The reaction was allowed to run for seven days. The two
compounds that were initially formed, at low conversion were isolated by semi-
preparative HPLC and characterized.

Through various spectroscopic evidence, the structure of the first peak isolated on
HPLC was confirmed as being A. The 1H-NMR spectrum shows two distinct olefmic
protons with chemical shifts characteristic of enol ethers, and carbonyl proton. The
presence of a carbonyl carbon is confirmed by IR which shows a carbonyl stretch at 1684

—1
cm .

18

 

 

Ugh» “A

 

 

 

a... , ll

 

”I
J

I

 

 

l ”L

 

Figure 10. lH-NMR of compound A

 

o... H N n v m u h o a on an «H

I l I. I l: I all bl . 'n l- P'— t-II

 

 

 

 

Figure 11. 'H-NMR of compound B
20

Figure 12. Structure of compound A

Proton decoupling NMR experiment shows Hb coupling with Ha and He, He coupling
with Hb and Hd. Coupling can also be seen between He and Hf.

Compound B

The second compound was isolated and characterized in the similar fashion by NMR, IR

and proton decoupling.

Wfi

Figure 13. Structure of compound B

From absorption pattern and NMR data it can be concluded that the two
compounds are isomers. J value fiom the NMR data also suggests that A is the trans
isomer with respect to the olefinic double bond (J=14.0Hz) and B is the cis isomer
(J=9.3Hz). The third product that appears after higher conversion was not identified.

Based on our knowledge of kinetics of hydrogen abstraction and cyclopropyl ring

opening, we can propose the following mechanism for the reaction. Since the products

21

are derived from a biradical species, we can safely assume the reaction to be occuring

from the triplet (n, n*) state, the product formation would be different if the reaction were

to go through the singlet state.

0

OH
313 nm
O/\V ________> . DAV
benzene L
(
OH
©/i\/\ M disproportionation
—-> 0 ° 4 A & B

cis + trans

 

Figure 14. Proposed mechanism for product formation

Quantum Yield

Quantum yields for formation of both the compounds A and B were measured at
room temperature. A 0.05 M solution of B-cyclopropylmethoxypropiophenone was
irradiated in benzene at 313 nm, with 0.1 M valerophenone solution as actinometer. The
yield was measured on HPLC. The observed quantum yield was 0.09 for the cis isomer
and 0.14 for the trans isomer as compared to 0.49 (cis and trans oxacyclopentanols)
formed from B-ethoxypropiophenone.

The quantum yield of product formation appears to be low because 1,5 biradicals
ofien disproportionate to the enol of the starting ketone and then reketonize rapidly.
Previous studies have indicated that the 1,5 biradical generated photochemically from

B-ethoxypropiophenone," undergoes internal disproportionation by two pathways, 1,6—H

22

transfer which generates the starting ketone and 1,4—H transfer, the major pathway,
generating the enol of the starting compound. The 7 oxygen in the molecule imparts a
unique characteristic wherein the five-atom transition state leading to the enol is free of
any significant eclipsing interaction. Only two products were obtained from the reaction,
the (Z) and (E)-oxacyclopentanols. Photochemistry of o-(cyclopropylmethoxy)
benzophenone also shows formation of the cyclopentanol ring with a quantum yield of
0.26; some formation (7% chemical yield) of the cyclooctenol was also observed.‘8 But
no product derived from the biradical with trans double bond was obtained, as opposed to
CMP, where we obtained both the cis and trans double bond. In our present system, there
was no cyclopentanol formation. This is because of the competition between cyclization
of the biradical and high rate of radical opening of the cyclopropyl ring. The rate of

cyclopropyl ring opening is generally on the order of 108 5".27

Quenching Study

A quenching study was carried out on a 0.028 M solution in benzene d6 with 2,
5-dimethylhexa—2,4-diene as the quencher. A 0.01 M solution of valerophenone was
used as the actinometer. The ampoules holding the sample were placed in a
merry-go-round setup, at room temperature and irradiated at 313 nm for five hours.
Analysis was carried out using HPLC. Values of 360 and 215 for kq'c were obtained from
the Stern-Volmer plots. As discussed in the introduction, the reciprocal of t is equal to

the rate constant of hydrogen abstraction. Based on kq=6x109 M"s'l quenching study

23

shows the rate of triplet ketone deca to be about 2X107 s’l as com ared to that measured
y P

for B-ethoxypropiohenone and 2x109 3'1 measured for a-ethoxyacetophenone

 

 

 

 

16
14 4 y = 360.8x + 0.824
12 1 R2 = 0.9821 °
6 10 T
B 8 .
9 6 q .
4 ..
g 1 T r T F
0 0.01 0.02 0.03 0.04 0.05
G [M]

Figure 15. Stern Volmer quenching results for compound A

 

y = 215.07x + 0.8684
R2 = 0.9951

    

(Do/0
a)

 

 

 

o f T I T T

0 0.01 0.02 0.03 0.04 0.05
01M]

Figure 16. Stem Volmer quenching results for compound B

24

In the present system only products from ring opening are observed and thus it
can be assumed that the lifetime of the biradical in this case is considerably long. We
cannot predict the exact lifetime of the biradical, but based on the radical clock technique,
which takes into account all the products formed from the biradical and uses the rate of
formation of the products to calculate the lifetime of the biradical, we can propose that
the lifetime of our biradical is closer to 50 ns, assuming minimal formation of the
cyclization product. It is perplexing however, that no cyclization is observed inspite of
the presence of the oxygen atom. Moreover a total quantum yield of 0.26, and no other
product formed, means that 74% of reversal to the starting ketone is observed. To revert
to the starting ketone, the biradical has to go through a cyclic transition state, so it is
surprising that no cyclization products are formed.

In conclusion radical rearrangement is the only observed process, followed by
disproportionation to yield the two products, through a considerably long lived biradical.
Oxygen does not seem to play a role deciding the fate of the biradical, contrary to
expectations. The trans isomer would be expected to cyclize into an eight membered

ring, but probably does not due to the competing disproportionation.

25

Photochemistry of o-benzyl benzophenone

A 0.01 M sample of o-BzBP was irradiated in acetonitrile-d4, toluene-d8 and methanol-d4,
at 0°C and temperature of dry ice. Irradiation was done in a medium pressure mercury
lamp (Pyrex filtered). The samples turned greenish-yellow on irradiation. It took 1hr and
40 minutes for the reaction to go to completion with the formation of o-BzBP-ECB at
0°C in toluene-d3. It took approximately similar time frame in the other solvents.
Sobzack has previously characterized the structure and thus the 1H-NMR and l3C-NMR
structures were compared to his results. In toluene-d3 the benzylic methylene at 4.03
ppm disappeared and a new singlet appeared at 4.71 ppm There is also appearance of
another singlet at 2.21 ppm, which is the hydroxy group. The l3C-NMR shows two
distinct aliphatic resonances, which are consistent with the o-BzBP-ECB structure. The
sample was stable at dry ice temperature but reverted back to the starting ketone at room

temperature. A significant yellow-green fluorescence was retained even on reversal to

the ketone.

 

0
Ph
4‘
O O hv, Pyrex IIOH
___> 5
o ; Ph
0 C H
o-BZBP o-BZBP-EC B

Figure 17. Photochemistry of BZBP

26

 

 

 

 

l

 

A 4 AL
' V ' K
a

O
erva"erl’vfrf‘VTYTerTijvaer’fY'vvir‘fvv

 

. L

T.

V'vvvviv'Yf‘rr'Terfr‘y

 

 

 

 

 

 

Lapin...

YI'fYT‘VfYV‘VY'YTVVV"

L

f'rr'Tvv'f'VVrvrvv‘verrVVTTIererfoIrrrf‘

Figure 18. IH-NMR for BzBP in toluene-d6 Before (A) and After (B) irradiation

27

Degassed solid o-BzBP was irradiated under medium pressure mercury lamp.
lH-NMR was taken of its CDCl3 solution. No significant change was observed in the
spectrum after four hours, but the color of the solid turned a light shade of yellow. After
longer irradiation period, i.e. 20 hours, two singlets appear at 4.96 and 4.99 ppm. The
color of the solid becomes more intense. The conversion is very low. The two peaks can
be assigned to the two benzylic methylene protons in — o-BzBP-ECB and o-BzBP-ZCB,
respectively, based on the characterization by Sobzack.29 The o-BzBP—ECB hydroxy
group appears at 2.25 ppm and for the Z-isomer appears at 2.9 ppm. The Z isomer is
short lived, because lH-NMR of the same sample, stored at 0°C, for 4 hrs. shows

considerable decrease and near disappearance of the peaks at 4.99 and 2.9 ppm.

 

 

 

 

 

 

 

 

O 2.25 ('9
pn/ OH
0 0.24. .\ n
/ +
3 Ph / ; Ph
H\ H
O 4.96 \ 4.99
o-BZBP (solid) o-BZBP-ECB o-BZBP-ZCB

Figure 19. Irradiation of solid BZBP

Though the lH-NMR shows formation of only two products, when the sample is
injected into HPLC, there is another product observed, whose intensity is more than that
for the o-BzBP-ECB and o—BzBP-ZCB. This peak was isolated on HPLC and

characterized by 1H-NMR and mass spectroscopy.

28

From the absence of the methylene proton and presence of aromatic protons only,
m lH-NMR and the distinct m/z peak at 286.0 and other mass peaks, this compound was
identified as o-dibenzoyl benzene. In spite of rigorous degassing, there was some
oxygen, which probably gave this result. O-BzBP is a low melting solid, which is

clumpy in nature and must have trapped the oxygen.

OH h" C/ CH
Ph —>
C\
CH;

11.5“

 

 

 

 

 

 

 

 

 

Hg h
\ T
/ ph ‘____'
/
\ Ph
m: Ph ”CB
[:[coph P11, 0H
[:[COPh C\ /
t-CB P“

Figure 20. Formation of the four o-xylylenols and benzocyclobutenols

Photoenolization and the chronology of benzocyclobutenol formation has been
studied by the Wagner group for some time, especially with respect to substituent effects.
Factors that affect this chronology are 1) initial geometry for hydrogen abstraction; 2)
nature of excited state; 3) lifetime of the biradical; 4) fate of the o-xylylenols; 5) stability

of benzocyclobutenols.

29

Various studies, like trapping experiments with maleic anhydride and oxygen,
kinetic data and computational studies provided more insight into the formation of the
ortho-xylylenols. The results seem to support the mechanism which shows formation of
four different geometries of the triplet biradical, yielding four different ortho-xylylenols.

In solution the photoreaction is very stereoselective which is confirmed by the
Diels-Alder reaction when o-BzBP is irradiated in presence of MA. Brief irradiation
converts the o-BzBP quantitatively into c-CB.

From our results, it is observed that in the solid state, the stereoselectivity of
cyclobutenol formation is lost. When the 1H-NMR is taken as soon as irradiation is
complete and the tube stored at 0°C, formation of both the isomers is seen. When left in
solution for several hours the NMR peak for the t-CB disappears, which probably goes to

the EZ xylylenol and forms the o-drbenzoyl benzene or the starting ketone.

30

EXPERIMENTAL

General Procedures

lH-NMR, l3C-NMR, proton decoupling, DEPT and hetero-COSY spectra were
obtained using Varian Gemini 300 MHz and VXR 500 MHz spectrophotometers, with
VXNMR software. Deuterated solvents used were obtained from Aldrich Chemical.
Chemical shifts were measured relative to chloroform-d, (7.24 ppm for 1H and 77.0 ppm
for I3C), benzene-d6 (7.10 ppm for lH-NMR) and toluene-d3 (2.09 ppm for 'H). Fourier
Transform Infrared spectra were obtained using a Nicolet IR/42. Samples were prepared
in a 0.025mm solution cell with carbon tetrachloride as solvent or on NaCl plates using
chloroform as the solvent. UV-VIS absorption spectra were obtained on a Shimadzu UV-
160 spectrophotometer with matched 1.0 cm quartz cells. Low resolution mass spectra
were recorded using a Hewlett Packard 5890 GC/MS. Gas Chromatograpic analyses
were performed on a Varian 3400 chromatograph equipped with flame ionization
detector. HPLC analyses were conducted on a Rainin system equipped with a two
solvent delivery pumps, a UV detector, a 20 pL loop and a normal phase Microsorb Si80-
125-CS column. The data were acquired using a Dell PC. Melting point was determined

using a capillary Uni-Melt melting point apparatus.

31

Synthesis

A. B-Cyclopropylmethoxypropiophenone

CMP was made in a simple two step manner according to the following scheme.

(53%)

cyclopropyl
methanol
reflux

WW

(89%)
Scheme 5. Synthesis of CMP

,B-iodopropiophenone (IP)

Standard literature method was used to carry out the first step.27 To a solution of
16.17 g (0.1078 moles) of sodium iodide in 25 mL of anhydrous acetone was added a
solution of 2.175 g (0.013 moles) of previously recrystallized B-chloropropiophenone
(from petroleum ether) in 75 mL of anhydrous acetone. The solution was refluxed for 5
hours and then concentrated under reduced pressure to afford a solid residue. This
residue was triturated with ether. The ether was then filtered to remove any traces of

sodium chloride. Upon distilling off the ether, 3 solid residue was obtained which was

32

recrystallized from petroleum ether to yield 1.94 g of pure B-iodopropiophenone (53%)

as a slightly yellow colored solid which melted at 61-63°C air?“a mp 61-62°C).
‘H-NMR (CDC13, 300 MHz) 8 ppm: 3.46 (t, 2H), 3.62 (t, 2H), 7.42-7.62 (m, 3H), 7.92

(d, 2H).

,6-(cyclopropylmethoxy)pr0piophenone (CMP)

0.5 g (1.92 moles) of [P was then refluxed with 16 mL (0.2 mole) of
cyclopropylmethanol for 16 hours. The excess cyclopropylmethanol was distilled off
leaving behind the crude product. The material was purified by column chromatography
using a 77 : 13 mixture of hexane and ethyl acetate. Chromatography for the second time
with the same eluant yielded 0.35 g (1.72 moles) of pure CMP (89% yield).
Characterization was done using NMR, l3C-NMR, Hetero-COSY, proton decoupling
experiments, DEPT and mass spectroscopy
'H-NMR (CDC13, 300 MHz) 8 ppm: 0.16 (dd, 2H, J = 5.4 Hz, 8.01Hz), 0.49 (dd, 2H, J =
5.4 Hz, 8.01Hz), 1.02 (ttt, 1H, J = 6.6 Hz), 3.25 (t, 2H, J = 7.3 Hz), 3.28 (d, 2H, J = 6.6
Hz), 3.84 (t, 2H, J = 7.3 Hz), 7.4-7.6 (m, 3H), 7.93 (d, 2H)

”C-NMR (CDC13, 75MHz) 6 ppm: 2.98, 10.5, 38.8, 65.7, 75.9, 128, 128.5, 133.1, 170.0,
198.0.

GC-MS (m/z): 204 (100%), 203 (M), 133, 105, 77.

DEPT spectra accounts for four secondary carbons (two equivalent) and four tertiary
carbons (four equivalent).

FTIR (CHC13, cm“) 3020 (s), 1684 (m-s), 1215 (s)

33

PP‘“

 

 

20

 

4O

60

 

80

100

120

 

 

I
140

l
160

  

IIIIII"|II

180

lll‘llilll

200

Figure 21. Ii’C-NMR of B-cyclopropylmethoxypropiophenone

34

 

 

n]

l.

.J
65
t9 9 ‘

C
'l

1.1
‘1‘ ‘1"?

0.
it if:

 

-—4—er 11-10
“"1 f 1'

 

 

 

 

Figure 22. Hetero-COSY spectrum of CMP

B. O-Benzyl benzophenone

BZBP was made according to the following scheme.

81' NBS 8' AIC13 3' 1) Ms/Eteo
——. _—,
a CC14 benzene 2) C410,
CH3 3)benzoyl
Br p11 chloride

Scheme 6. Synthesis of BZBP

 

 

35

2-br0mobenzylbromide

To a 500 mL flask was added 45.5 g (0.25 mole) of 2-bromotoluene (Aldrich), 42
g (0.24 mole) of N-bromosuccinimide and 200 mL of carbon tetrachloride. 0.25 g of
benzoyl peroxide was added to the flask, with a very strong (400 watts) light shining on
the reaction vessel during addition. The reaction was allowed to reflux overnight, with
the light still on. The succinirnide was filtered off and carbon tetrachloride was removed
by rotory evaporation. The crude product was allowed to stand undisturbed in the
refrigerator for several hours to obtain crystals of 2-bromobenzyl bromide. 2-
Bromotoluene was poured off from the top and the remaining crystals were rinsed and
filtered several times with hexanes to yield 49.1 g (80%) of 2-bromobenzyl bromide as
white crystals.28b
lH-NMR (CDC13, 300 MHz) 8 ppm: 4.6(s, 2H), 7.15 (ddd, J=7.7, 7.6, 1.8 Hz 1H), 7.44

(dd, 7.6, 1.7Hz, 1H), 7.56 (d, 7.7 Hz, 1H).

Z-bromodiphenylmethane

The reaction flask, under argon, was charged with 12.5 g ( 0.08 mole) of
aluminum trichloride and 100 ml of 1,2 dichloroethane and cooled to 0°C with stirring.
24.5 g (0.1 mole) of 2 bromobenzyl bromide was then added and the reaction flask
cooled to -40°C. To this a mixture of 23.4 gms (0.3 mole) of dry benzene and 25 mL of
1,2 dichloroethane was added over a period of 15 minute via a syringe. The reaction was
allowed to stir for four hours at 0°C. It was then quenched by pouring the contents of the
flask into a mixture of 100 g of crushed ice and 100 mL of aq. HCl. This mixture was

extracted with three 50 mL aliquots of ether. The ether layer was washed with saturated

36

sodium bicarbonate solution until neutral and then dried over anhydrous sodium sulfate.
The crude product was purified by column chromatography, by first eluting with hexanes
to remove diphenyl methane, followed by 90:10 mixture of hexane and ethyl acetate. 6.2
g (25.3%) of pure 2-bromodiphenyl methane was obtained as white crystalline powder.28b

'H-NMR (CDC13, 300 MHz) 6 ppm: 4.10 (s, 2H), 7.06(m, 8H), 7.6 (dd, 1H).

2-benzyl benzophenone

Under argon, 2.3 g (9.4mmoles) of 2-bromodiphenyl methane was added to 5ml
of anhydrous ether and 0.238 g (9.9 moles) of magnesium metal. A few crystals of
iodine were added and the mixture stirred vigorously to initiate the complex formation.
The reaction flask was warmed to reflux for 10 minutes followed by cooling to room
temperature. 0.916 g of dry CdClz was then added and the mixture refluxed for an
additional 1 hour. The ether was then distilled off and 10 mL of anhydrous toluene
added. 0.983 g (7.1 moles) of benzoyl chloride in 7 ml of toluene was then added to
the reaction at room temperature, upon complete addition the reaction was allowed to
reflux for 3 hours then worked up in water and dilute sulfuric acid. The organic phase
was separated and the aqueous phase was extracted 3 times with toluene, the combined
toluene layers were washed with water, 5% sodium bicarbonate solution, again with
water and finally brine. It was then dried over anhydrous sodium sulfate and the toluene
was removed by rotory evaporation. The crude product was purified by column
chromatography two times using 85:15 mixture of hexane and ethyl acetate as eluant
followed by recrystallization using petroleum ether. 1.09 gms (43%) of pure white

product was obtained which melted at 48-50°C, lit.28c 505m.

37

'H-NMR (CDC13, 300 MHz) 6 ppm: 4.09 (s, 2H), 7.05-7.15 (m, 4H), 7.2—7.3 (m, 4H),
7.3-7.4 (m, 3H), 7. 57.52 (distorted ddd, 1H), 7.68-7.71 (m, 2H).

”C-NMR (c0013, 75 MHz) 6 ppm: 38.84, 125.6, 126.02, 128.26, 128.31, 128.65,
129.19,130.17, 130.34,130.82, 133.14,137.63, 138.8, 1400,1405, 199.0.

LRMS, m/z: 272.2 (100%), 271 (W), 194, 165, 105, 77.

UV (mm... (c m... M")): 248 (15,200), 211(21,700).

38

Photochemistry of CMP

O

O
hv,3l3nm
Mow-“z 0“

  “kmi

Figure 23. Photochemistry of CMP

lH-NMR experiment

This experiment was repeated several times for reproducibility. The reaction was
sensitive to irradiation time.
In a typical experiment a 0.05M solution (10.2 mg/mL in benzene-d6) was first degassed
by passing argon through it for one hour in an NMR tube. Irradiation was conducted at
313 nm filtered light at room temperature. The 313 nm light was isolated fiom a medium
pressure 450 W Hanovia mercury arc lamp by using a solution of alkaline potassium
chromate (0.002 M K2Cr04 in 1% aq. potassium carbonate) as the filter. The tube was
suspended close to the light source and together with the light source was loosely
wrapped in foil. The reaction was followed by lH-NMR. The reaction proceeded slowly.
Appearance of peaks at 6.2 ppm and 4.97 ppm for the first 24 hours seemed to slowly
diminish after that. The reaction was later carried out on a larger scale by irradiating

5mL of 0.05M solution, and the products at low conversion, i.e afler five hours of

39

irradiation, were isolated and identified as cyclopropyl ring opened products A and B in a
yield of about 4% each. Isolation was carried out using HPLC (Rainin system equipped
with two solvent delivery pumps, Dynamax soflware and a UV detector, 100 pl loop and

a normal phase semi-prep Silica column), compounds A and B were eluted at about 11

and 14 minutes respectively and CMP was eluted at 24 minutes.

Compound A

IH-NMR (CDC13, 300 MHz) 8 ppm: 0.9 (t, 3H, J = 8.0 Hz), 1.95 (dt, 2H, J = 8.0, 14.6
Hz), 3.3 (t, 2H, J = 7.3 Hz), 4.12 (t, 2H, J = 7.3 Hz), 4.91 (m, 1H, J = 14, 14.6 Hz), 6.26
(d, 1HJ= 14 Hz), 7.47-7.57 (m, 3H), 8.0 (d, 2H).

Proton decoupling experiments were carried out to correctly identify the sample.

FTIR (CHCI3, cm"). 3020 (s), 1684 (m-s), 1601 (m), 1452(5), 1437 (m), 1217 (vs).

The km“ is 277 nm in UV.

Compound B

'H-NMR (CDC13, 300 MHz) 8 ppm: 0.85 (t, 3H J = 8.0 Hz), 2.0 (dt, 2H J = 8.0, 14.6
Hz), 3.3 (t, 2H J= 7.2 Hz), 4.15 (t, 2H J= 7.2 Hz), 4.4 (m, 1H, J= 9.3 Hz), 5.9 (d, 1H, J
= 9.3, 14.6 Hz), 7.4—7.6(m, 3H), 8.0 (d, 2H).

Proton decoupling experiments were carried out to correctly identify the sample.

FTIR (CHCI3, cm"). 3020 (s), 1684 (s), 1599 (m), 1450(m), 1437(m), 1219 (vs).

The km“ is 278 nm in UV.

40

Quantum Yield

Quantum yield was studied for formation of the two isomers. Formation of
acetophenone from valerophenone was used as the stande to calculate the intensity of
the light absorbed. Hexadecane was used as the internal standard and the analysis was
carried out by gas chromatography. The gas chromatograph used was Varian 3400, with
3392A integrator. The column used was DB-210, the temperature of which was set at
200°C. The temperature of the injector was 200°C and that of the detector was set at
220°C. The pressure of the carrier gas, helium was 80 lbs per square inch. The
acetophenone peak appeared after 19.4 minutes, followed by the hexadecane at 22.7
minutes and lastly the valerophenone at 25.6 minutes.

Special precaution was taken for cleaning all the glassware used for the
experiment. Ampoules used were prepared from Pyrex culture tubes. The instrument
used for analysis of the photoproducts from CMP was HPLC (Varian with Dynamax
sofiware and UV detector, a normal phase Si column and a 20111 loop, with the flow rate
of 0.8ml/min). The solvent used was a 98:2 mixture of hexane and ethyl acetate, with
this solvent mixture and the above conditions, the retention time for compound A was
about 4.2 minutes, for compound B was 6.5 minutes, the internal standard, methyl
benzoate appeared at 7.1 minutes and B-cyclopropylmethoxypropiophenone appeared at
20 minutes.

The instrumental response factor was calculated using various concentrations of
the analyte versus a single concentration of internal standard. Response factor was

calculated according to the equation:

41

 

that was pre-evacuated for about an hour. The sample tubes were then fiozen in liquid
nitrogen and evacuated, the stopcocks on the vacuum lines were then closed and the tubes
allowed to warm to room temperature. The fi‘eeze-pump-thaw cycle was conducted four
times and the tubes were then sealed while still under vacuum.

The irradiation was done at 313 nm filtered light, in which the light source was
mounted in the center of a merry-go-round setup. The ampoules Were then loaded in the
holes of the setup and irradiated for 5 hours.

The quantum yields were calculated using equation 4

<1) = [PP] /1

Equation 4.
The intensity of light is determined from equation 5, since [AP] is known

I = [AP] / 0.33

Equation 5.

The concentration of photoproduct is calculated from equation 6
[PP] = RtPP * [IS] * (APP / Als)

Equation 6.

Quenching Studies

Stern-Volmer quenching studies were carried out using 2,5 dimethyl-2,4-
hexadiene as the triplet quencher. Sampling was done in the similar manner to quantum
yield studies. The ampoules were charged with known concentration of CMP and
internal standard (methyl benzoate) and various concentrations of the quencher, the first

ampoule contained no quencher. The ampoules were degassed by the freeze-pump—thaw

42

(I) = [PP] / I
Equation 4.
The intensity of light is determined from equation 5, since [AP] is known
I = [AP] / 0.33
Equation 5.

The concentration of photoproduct is calculated from equation 6

[PP] = RfPP * [IS] * (APP / A15)

 

 

 

 

 

Equation 6.
sample Photoproduct(PP) %Area (PP) %Area (IS) [PP] (D
1 Compound A inj.l 1.662 7.443 2.13x10'5 0.09
Compound A inj.2 1.608 7.270 2.11x10'5 0.09
2 Compound B in] 1 2.940 7.443 3.54x10'5 0.14
Compound B in] 2 2.883 7.270 3.5531105 0.14

 

 

 

 

 

 

 

 

ACT = VP, [VP] = 0.099 M, IsACT = HD, [18m] = 0.001 M, [ketone] = 0.0499 M,
18m = MB, [18m] = 0.00069 M, I = 0.000239, Irradiation time = 5 hrs., 2. = 313 nm,
anmmg 1.89, RfA=0.1384

Quenching Studies

Stern-Volmer quenching studies were carried out using 2,5-dimethyl-2,4-
hexadiene as the triplet quencher. Sampling was done in the similar manner to quantum
yield studies. The ampoules were charged with known concentration of CMP and
internal standard (methyl benzoate) and various concentrations of the quencher, the first

ampoule contained no quencher. The ampoules were degassed by the fi'eeze-pump-thaw

43

method and then set on the merry-go-round apparatus and irradiated at 313 nm for 5

hours. Analysis was done in a manner similar to that for quantum yield studies. The

Stem-Volmer expression is
(Do/(D =1 +kq[Q]T°

Equation 7.

(Do is the quantum yield without the quencher

(D is the quanttun yield in the presence of the quencher

[Q] is the concentration of the quencher

kq is the bimolecular rate constant for quenching
To is the lifetime of the excited state being quenched

The quenching is assumed to be diffirsion controlled with a rate constant of 6x109 M's".

Photochemistry of BZBP
Experiment I

The photoreaction was carried out in an NMR tube. The experiment was repeated
several times to ensure repeatability. A 0.01M solution of BZBP in toluene-d3 was first
degassed and then irradiated with a Pyrex filtered light using a medium pressure mercury
arc lamp. The reaction was sensitive to temperature and thus the temperature was

maintained at 0°C. The reaction was completed in 1 hour and 40 minutes, as indicated by

the disappearance of the singlet at 4.02 ppm and formation of two new singlets at 4.75
ppm and 2.2 ppm (broad). The product had the same lH-NMR as BZBP-ECB (on the
basis of previous lH-NMR characterization by Sobczak, in which he had washed the
sample with D20, upon which the broad peak at 2.2 ppm disappeared indicating it was a

hydroxy group). The solution in the NMR tube was a fluorescent yellow-green color.

 

Ph

0
HO
Ph hv, Pyrex ’c’Ph
————>
I .\\H
\
Ph

BZBP BZBP-EC B

Experiment 2

Irradiation of Solid BZBP

In an ampoule, prepared similar to those for quantum yield studies, a finely
powdered, 10 mg sample of solid BZBP was weighed out. The sample was dispersed
evenly at the bottom of the tube. The solid was then degassed on the vacuum setup for an
hour and the ampoule sealed while still under vacuum. Several such ampoules were
prepared. The samples were irradiated at room temperature with Pyrex filtered light from
a medium pressure mercury lamp. The color of the solid turned lemon yellow on
irradiation almost within the first 30 minutes. The ampoules were opened in a dry box,
the sample dissolved in CDCl;; and transferred to NMR tubes. The NMR tubes were kept
at 0°C, till spectrum was achieved. The sample was irradiated in increments of one hour
for the first four hours, with no significant change in the 1H-NMR. On irradiation for 20

hours, the IH--NMR showed formation of both the isomers BZBP-ECB and BZBP-ZCB.

45

On irradiating it for upto 48 hours, no more change was observed. The two isomers were
characterized by Sobczak earlier, and assignments of the peaks were based on that
characterization. Formation of benzoyl benzophenone was confirmed by isolating on
HPLC using a 95:10 mixture of hexanezethyl acetate (the retention time for the peak was
10 mins. on a Si80-l25-CS column), followed by lH-NMR spectroscopy and LRMS.
The lH-NMR sample shows only aromatic hydrogens, the same sample when submitted

for mass spectral analysis gave an m/z peak at 286 which is consistent with benzoyl

benzophenone.

46

10.

11.

12.

13.

14.

15.

REFERENCES

. Cowen, D.O.; Drisco, R. L. Elements of Organic Photochemistry; Academic Press:

New York, 1969.

Wagner, P. J. Topics In Current Chemistry 1976, 66.

. a) Wagner, P. J. Acc. Chem. Res. 1971, 4, 168. b) Wagner, P. J.; Meador, M. A.;

Park, B. S. J. Am. Chem. Soc. 1990, 112, 5199. c) Wagner, P. J.; Zhou, B.;
Hasegawa, T; Ward D. L. J. Am. Chem. Soc. 1991, 113, 9640. d) Wagner, P.J.;
Kochevar, I. J. Am. Chem. Soc. 1968, 90, 2232.

a) Dewar, M. J. S.; Doubleday, C. J. Am. Chem. Soc. 1978, 100, 4935. b) Wagner, P.
J.; Hammond, G. S. J. Am. Chem. Soc. 1965, 87, 4009.

Turro, N. J.; Weiss, D. S. J. Am. Chem. Soc. 1968, 90, 2185.

Scheffer, J. R.; Dzakpasu, A. A. J. Am. Chem. Soc. 1978, 100, 2163.

Shaffner, J. R. Organic Photochemistry, 1987, 8, 249.

Wagner, P. J.; Kelso, P.; Kemppainen, A. K.; Zepp, R. J. Am. Chem. Soc. 1972, 94,
7500.

Small, R. D.; Sciano, J. C. Chem. Phys. Lett. 1977, 50, 431.

Shimizu, N.; Ishikawa, M.; Ishikura, K.; Nishida, S. J. Am. Chem. Soc. 1974, 96,
6456

Caldwell, R; Majima, T.; Pac, C. J. Am. Chem. Soc. 1982, 104, 629.

Freilich, S.; Peters, K. J. Am. Chem. Soc. 1981, 103, 6255.

Wagner, P. J.; Zepp, R. G. J. Am. Chem. Soc. 1971, 93, 4958.

Horspool, W. M. Photochemistry in Organic Synthesis, J. D. Coyle Ed, 1986, No. 57.

Wagner P. J. Acc. Chem. Res. 1989, 22, 83.

47

16. Wagner, P. J.; Giri, B.P.; Scaiano J. C.; Ward, D. L.; Gabe, E.; Lee, F. L. J. Am.
Chem. Soc. 1985, 107, 5484.

17. Wagner, P. J.; Jang, J. S. J. Am. Chem. Soc. 1993, 115, 7914.

18. a) Wagner, P. J.; Chiu, C. J. Am. Chem. Soc. 1979, 101, 7134. b) Wagner, P.J.; Liu,
K-C, Noguchi, Y. J. Am. Chem. Soc. 1981, 103, 3837. c) Doubleday, C.; Turro, N. J .;
Wang, J.-F. Acc. Chem Res. 1989, 22, 199. d) Wagner, P. J.; Kemppainen, A. E. J.
Am. Chem. Soc. 1968, 90, 5896.

19. a) Meador, M. A.; Wagner, P. J. J. Org. Chem. 1985, 50, 419. b) Winnik, M. A.; Lee,
C. K.; Basu, S.; Saunders, D. S. J. Am. Chem. Soc. 1974, 96, 6182.

20. Beckett, A.; Porter, G. Trans. Faraday Soc. 1963, 58, 2038.

21. Sammes, P. G. Tetrahedron 1976, 32, 405.

22. Beckett, A.; Porter, G. Trans. Faraday Soc. 1963, 58, 2051.

23. Yang, N. C.; Rivas, C. J. J. Am. Chem. Soc. 1961, 2213.

24. Matsurra, T.; Kitaura, Y. Tetrahedron 1971, 27, 1597-1606.

25. Arnold, B. J.; Sammes, P. G.; Wallace, T. W. J. Chem. Soc. Perkin 1 1974, 410.

26. a) Wagner, P. J.; Sobczak, M. Tetrahedron Lett., 1998, 39, 2523- 2526. b) Wagner P.
J.; Subrahmanyam, D.; Park, B. S. J. Am. Chem. Soc. 1991, 113, 709.

27. Bowry, V.; Lusztyk, J.; Ingold, K. J. Am. Chem. Soc. 1991, 113, 5687.

28. a) Kim, J.; Bogdan, M.; Mariano, P. J. Am. Chem. Soc. 1991, 113, 9251. b) Sobczak,
M., Ph. D. dissertation, Michigan State University, 1997. c) Bradsher, C. K J. Am.
Chem. Soc. 1940, 62, 486.

29. Hale, W. J.; Britton, E. C. J. Am. Chem. Soc. 1919, 41, 841.

48

   

1‘11‘11‘1\lll1.111111111131111l11111 1'11
3 1293 02177 8620