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University Microfilms International 300 North Zeeb Road Ann Arbor. Michigan 48106 USA St. John's Road, Tyler's Careen High Wycombe, Bucks, England HP10 8HR I\ 78-12,372
NAGARAJAN, Madhavarao, 1951- CARBENIC AND CATICNIC REACTIONS OF 3-DIAZO-2, 5-DIPHENYLFVRROLE.
The Ohio State University, Ph.D., 1978 Chemistry, organic
University Microfilms International, Ann Arbor, Michigan 48ioe CARBENIC AND CATIONIC REACTIONS OF
3-DIAZO-2,5-DIPHENYLPYRROLE
Dissertation
Presented in Partial Fulfillment of the Requirements
for the Degree Doctor of Philosophy in the
Graduate School of The Ohio State University
By
M. Nagarajan, B.Sc., M.Sc,
* * * * *
The Ohio State University
1978
Reading Committee: Approved by Dr. H. Shechter Dr. L. A. Paquette Dr. J. A. Secrist III
Adviser Department of Chemistry To my family ACKNOWLEDGMENT
I wish to express my thanks to Dr. Harold Shechter for his help and advice during the course of this research and his expert guidance in preparing this dissertation.
To my colleagues, especially Drs. P.J. Card, T.V.
Rajan Babu, K.T. Chang, Ms. Mridula Nair and Mr. P.R.
Menard, I express my appreciation for their help and encouragement. Financial support from The National
Institute of Health, The National Science Foundation, The
Stauffer Chemical Company, and The Ohio State University is gratefully acknowledged.
iii VITA
June 17, 1951 ...... Born, Madras, India
197 ...... B.Sc., University of Madras, Madras, India
1973 . M.Sc., Indian Institute of Technology, Madras, India 1 9 7 3 - 1 9 7 5 ...... Teaching Associate, The Ohio State University, Columbus, Ohio
1975 - 1976 ...... Research Associate, 19//1977 - oresentpresent TheColumbus, Ohio state Ohio University,
1976 - 1977 ...... Stauffer Chemical Company Fellow, The Ohio State University, Columbus, Ohio
FIELD OF STUDY
Organic Chemistry TABLE OF CONTENTS Page
ACKNOWLEDGMENTS...... iii
VITA ...... iv
Chapter
STATEMENT OF THE PROBLEM ...... 1
I. HISTORICAL...... 2 II. RESULTS AND DISCUSSION ...... 19
III. EXPERIMENTAL...... 95 REFERENCES ...... 149
V STATEMENT OF PROBLEM
The present study is an investigation of the chemistry of 3-diazo-2,5-diphenylpyrrole (1), 2,5-diphenyl-3H- pyrrolylidene (2), and 2, 5-diphenylpyrrole-3-diazonium salts
<3)* ©v0 ^ ^
j s - a . C6H5 N C6H5 S V " C6H5 C6H5 X N ^ C6H5
. The principal objectives of this research were (a) to determine the products of thermal and photolytic reactions of 1, 2, and 3 with various substrates; (b) to characterize the behaviour of 2 in its singlet (2s) and triplet (2t) iv 11
65 C -.H65 p . 65 65
2s 2t
states and (c) to explore the possibility of using the above reactions for advantageous purposes in synthetic organic chemistry.
1 CHAPTER I. HISTORICAL
In 1953, Doering and DePuy^ reported synthesis of diazocyclopentadiene (4). Unlike many other diazo compounds, 4 proved to be unusually stable. A principal reason for the stability of 4 is attributed to resonance in which the cyclopentadiene ring develops negative charge and an aromatic sextet as in 5. One of the logical
4 5 developments of 4 is its conversion to cyclopenta- dienylidene (6), a carbene of intense theoretical interest.
Like 4, 6 also has a canonical form 7 in which a cyclic
611 electron system can be attained. Calculations indicate2
6 7
1W. von E. Doering and C.H. DePuy, J. Am. Chem. Soc., 75, 5955 (1953). 2 R. Gleiter and R. Hoffmann, J. Am. Chem. Soc., 90, 5457 (1968).
2 3 that 6**7 is indeed stabilized and as such will have electrophilic properties. ESR studies# however, have conclusively established the ground state of 6 to be a 3 triplet.
The chemistry of 6 indicates that its reactions proceed through its singlet state. Thus, 6 adds to 4 5 olefins with retention of stereochemistry * (Eq. 1).
(1) 6
100%
Addition to p-substituted styrenes as in Eq. 2 results in a kinetic p value of -0.76 with a constants or p = -0.46 withct+ constants, thus revealing that 6 behaves as an 6 electrophile.
3 E. Wasserman, L. Barash, A.M. Trozzolo, R.W. Murray, and W.A. Yager, J. Am. Chem. Soc., 86, 2304 (1964).
*R.A. Moss, J. Ora. Chem., 31, 3296 (1966). 5 R.A. Moss, and J.R. Przybyla, J. Orq. Chem., 33, 3816 (1968). g H. Durr and F. Werndorff, Anqew. Chem. Intemat. Edn. 13, 483 (1974). 4
6 + X - ^ O y ~ CH=CH2 --- > (2)
Photolysis of 4 in benzene produces, presumably via
6, spironorcaradiene 8; 8, however, rearranges readily to Q bicyclo[6.3.0]undeca-[l , 2, 4,6, 9]-pentaene (11) via 7 spiro[6.4]undecapentaene 9 and thence 1£ (Eq. 3).
O hv 4 + @ 8 9 (3)
10 11
Di-, tri-, and tetraphenyldiazocyclopentadienes show Q Q behavior similar to 4. ' A likely explanation for the
singlet character of 6 and its phenyl derivatives is that
the carbenes are so reactive as generated that their
D. Schoenleber, Chem. Ber., 102, 1789 (1969).
8H. Durr and G. Scheppers, Chem. Ber.,103, 380 (1970). *H. Durr and L. Schrader, Chem. Ber., 102, 2026 (L969) . 5 intermolecular reactions occur faster than intersystem crossing to their triplet states.
Although 4 and its derivatives have been intensively researched, little is known of the chemistry of their heterocyclic analogs even though some of them have been known for a long time. Angelico synthesized 3-diazo-2,5- diphenylpyrrole (!L) and 3-diazo-2, 4,5-triphenylpyrrole
(lj2) by diazotizing their corresponding amines with nitrous acid and subsequent neutralization (Eq. 4).^°
(4) C,H ' c ^-h : Ca H- 6 5 jj 65 o 5 6 5
R = H 1 R = C,Hc 12 6 5 ~~~
Fischer and co-workers, in their investigation of porphyrins, prepared 2-carbethoxy-3,5-dimethylpyrrole-4- diazonium salts by diazotization of 4-amino-2-carbethoxy-
3,5-dimethylpyrrole.^
^ F . Angelico, Atti. Acad. Naz. Lincei., 14, II, 167 (1905) .
^ H . Fischer and A. Stern, Ann. Chem., 446, 229 (1926). 6
Synthesis of diazocyclopentadiene by routes which do not involve precursor amines prompted a search for related methods applicable to 5-membered heterocyclic systems. In
1960, 3-diazo-2,4,5-triphenylpyrrole (12) was prepared by reaction of 2,3,5-triphenylpyrrole and nitrous acid. 12
Application of this method to 2,5-diphenylpyrrole gave, however, 3-diazo-2,5-diphenylpyrrole (1) and 3-diazo-4- nitro-2,5-diphenylpyrrole, with the latter predominating.
This problem was overcome by the simple expedient of bubbling nitric oxide through a solution of 3-nitroso-2,5- diphenylpyrrole (Eq. 5).
Major Minor
(5)
1
12 J.M. Tedder and B. Webster, J. Chem. Soc., 3270 (1960). 7
About the same time# the procedure for preparing
3-amino-2,5-diphenylpyrrole was improved and then preparation of 3-diazo-2, 5-diphenylpyrrole (1_) by 13 diazotization and neutralization became practical. 14 Subsequently, Tedder and Webster showed that their method for introduction of a diazo group could be employed for synthesis of 2-diazopyrroles (Eq. 6) which cannot be prepared by diazotization because of the instability of the precursor amines.
C H C,H
r t no 3 j = c (6 )
The only attempts to extend the Doering-DePuy synthesis of diazocyclopentadiene to the pyrrole area are by Yoshida, 15 Hashimoto and Yoneda. These workers reacted pyrrole- magnesium bromide with p-toluenesulfonyl azide and obtained
2,21-azopyrrole. A possible mechanism for formation of the azopyrrole involves generation of 2-diazopyrrole in situ
13A. Kreutzberger and P. Kalter, J. Orq. Chem., 26, 3790 (1961) . 14 J.M. Tedder and B. Webster, J. Chem. Soc., 1638 (1962). 15 Z. Yoshida, H. Hashimoto, and S. Yoneda, Chem. Comm., 1344 (1971) . 8
which reacts further with the Grignard reagent to give the observed product (Eq. 7).
O + CH, S02n : ( MgBr (7) ON l MgBr O-—-ON N* H H
Very little is known about the chemistry of diazo- pyrroles. It is mentioned that 3-diazo-2,5-diphenylpyrrole
(.1) and 3-diazo-2, 4,5-triphenylpyrrole (1_2) are light sensitive, but no attempts were made to study the 16 products. Prolonged refluxing of 1J2 in dilute sulfuric 17 acid leads to .13 via intramolecular diazonium coupling
(Eq. 8).
HoSO. (8)
12 C 6H5 13
^ F . Angelico, Gazz. Chim. Ital., 53, 795 (1923) .
^ F . Angelico, Atti. R. Acad. Lincei., 17, 655 (1908) 9
An ethereal solution of h2 reacts with cyclooctyne, forming 2,3-cyclooctano-4,5,7-triphenylpyrazolo[l,5-c]- pyrimidine (1J5) through the intermediacy of the (3 + 2) 18 cycloaddition product 14 (Eq. 9).
12
14 (9) 1,5-shift
15
Diazopyrroles 1 and 12 do not undergo coupling reactions readily. However, fusion of 1^ and lj2 with
2-naphthol or refluxing a solution of the diazopyrrole and 2-naphthol in chloroform does give coupling 12 14 products ' as in Eq. 10.
IQ H. Durr, A.C. Ranade and I. Halberstadt, Synthesis, 878 (1974). 10
^ 2 OH N = N CHC1 OH - d * ( § © ' (10) c 6H 5 n C6H 5 6H 1
Analogously, 2,5-diphenylpyrrolyldiazonium salts couple 13 with various pyrroles at ot- and p-positions (Eq. 11) respectively. —A
® C 1 ® v w =« *’ CH. '-**3 1I2 - X\ rk H C6H5 N C6H5 S CH3 C6H5 g C6H5
(11) C6H5ty X /C6H5 N = N
H rd W * C,H_d N - Xl N 6 C6H 5 H C6H5 11
Only two reactions involving loss of nitrogen from a diazopyrrole are known 19 : 3-diazo-2,4,5-triphenyl pyrrole (12) on photolysis in benzene gives 2, 3, 4, 5- tetraphenylpyrrole; irradiation in methanol results in
2/3,5-triphenylpyrrole (1J5) (Eq. 12).
C6H 5S /C6H 5 C6H6
hv C6H5 £ C6H5 C6H5v / 2
(12) H 6 C6H 5 12
hv C6H5 H C6H5
16
It is speculated that insertion into benzene involves a carbenic process but no explanation is given as to the mechanism of reduction in methanol. Even less is known about 2-diazopyrroles other than that they couple with 2-naphthol 14 and that they are less stable than 3-diazopyrroles.
19 R.F. Bartholomew and J.M. Tedder, J. Chem. Soc.(C), 1601 (1968). 12
Diazopyrazoles have also been known for over 60 20 years. The first synthesis of a diazopyrazole, though not identified initially as such, is illustrated in Eq. 13. NH N S * 1) HNO V
C H ^>H 2) U3) 6 5 C,Hc£> b
It was not until the 1960's, however, that the chemistry of diazopyrazoles was advanced further. Various syntheses 21 22 of diazopyrazoles were developed by Farnum and Yates ' and by Reimlinger and coworkers 2 3 ' 24 and some of the reactions studied are summarized in Eq. 14.
90 E.V. Meyer, J. prakt. Chem., 90, 1 (1914). 21 D.G. Farnum and P. Yates, Chem. and Ind., 659 (1960).
22D.G. Farnum and P. Yates, J. Am. Chem. Soc., 84, 1399 (1962). 23H. Reimlinger, A. von Overstraeter, and H.G. Viehe, Chem. Ber., 94, 1036 (1961).
24H. Reimlinger and A. von Overstraeter, Chem. Ber., 99, 3350 (1966). 13
H20,CH3C0CH3 C6H5 V__
hv C6H5C° ' N''"H
(14)
C6H5CO C,Hc C£Hc D 3 , b D C6H6 H C,HcCO “ '6 5
Various substituted 3(5)-diazopyrazoles, synthesized by diazotization/neutralization of their corresponding 25 amines (Eq. 15), have been studied in this laboratory.
R - v NH, 1) HNO, *2 > - J 2 (15)
Rjr v 2) Na.CO, H
A particularly interesting observation is thermolysis of
3-diazo-4-methyl-5-phenylpyrazole to 2-cyano-2-methyl-3- phenyl-2H —azirine, acrylonitrile and benzonitrile (Eq. 16).
25 W.L. Magee and H. Shechter, J. Am. Chem. Soc., 99, 633 (1977). For fuller details see W.L. Magee, Ph.D. Thesis, The Ohio State University, Columbus, Ohio, 1974. 14
CH CN
+ ch2=chcn + c6h 5cn (16)
60% trace 10%
3-Diazo-5-phenylpyrazole (1J7) photolyses in ethyl ether to
5-ethoxy-l-ethyl-3-phenylpyrazole (18) and 3-ethoxy-1- ethyl-5-phenylpyrazole (19). While formation of 18 is easily accounted for in terms of oxonium intermediate 20 followed by ethyl migration/ the mechanism leading to 19 is not clear (Eq. 17). C^Hc
17 (17)
3-Diazopyrazoles react with electron-rich olefins with retention of nitrogen. Thus 5-t~butyl-3-diazopyrazole
(21) undergoes an apparent 1,4-cycloaddition with ethyl vinyl ether with elimination of ethanol to give 7-t- butylpyrazolo [3,2-c]-as-triazine quantitatively as shown in Eq. 18. Similarly, 21 adds to 1,1-dimethoxyethylene 15
N2 + CH2=CHOC2H5 t-C ,H, j r % t-C4H9 21 5 _c 2h 5o h (18)
-t—C 4 H9 forming 7-t-butyl-4, 4-dimethoxy-l, 4-dihydropyrazolo-
[3, 2-cl-as-triazine (Eq. 19).
21 + X 0C^3 CH-.0 OCHul:w3 (19) R
tautomerization
~ 4 9 CH3O 0 C H 3
Other 5-membered ring diazoheterocycles, especially those derived from imidazole are known. A representative 2 6 example is 4-diazoimidazole-5-carboxamide (22), derivatives of which are potent antitumor agents. The 27 photochemical reactions of 22 with alcohols have been of
26 Y.F. Shealy, R.F. Struck, L.B. Holum and J.A. Montgomery, J. Orq. Chem., 26, 2 396 (1961). 27U.G. Kang and H. Shechter, J. Am. Chem. Soc., 100, 651 (1978). recent interest because they result in C-H as well as
0-H insertion. Thus photolysis of 2J2 in ethanol yields,
in addition to imidazole-4-carboxamide and 5(4)- ethoxyimidazole-4{5)-carboxamide, 5(4)-(hydroxyalkyl)-
imidazole-4(5)-carboxamides (Eq. 20).
N
22 (32%) (20) ni3 OH
(39%) (2%) (2 7%)
It is presumed that these reactions involve the highly electrophilic singlet carbene 23 - 23a. 17
The very first diazoheterocycle of any kind to be 28 29 synthesized was 5-diazotetrazole. Some diazotriazoles have also been prepared but have not been studied comprehensively. An interesting application of 5-tetra- zolyldiazonium chloride is its pyrolysis to atomic carbon, 30 probably through the intermediacy of 5- diazotetrazole as illustrated in Eq. 21.
n 2+ci N 2 80° N NH ^ -HC1 w
31 32 Diazoindazole and some of its derivatives have been synthesized. When photolyzed in alcohols and benzene, diazoindazole undergoes reduction and insertion reactions respectively (Eq. 22). 2-Substituted-3-diazoindoles are
28 J. Thiele, Ann. Chem., 270, 46 (189 2).
29J.M. Tedder, in "Advances in Heterocyclic Chemistry," Vol. 8, A.R. Katritzky and A.J. Boulton, Eds., Academic Press, New York, 1967, page 18. 30. P.B. Shevlin, J. Am. Chem. Soc., 9^4, 1379 (1972).
31 E. Bamberger, Chem. Ber., 32, 1773 (1899). 32 U. Simon, O. SUs and L. Horner, Ann. Chem., 697, 17 (1966). 18 C 2H5OH hv n 0 + CH-.CHO N 3 2 H
C (22)
^ C H hv Ocr H also known and the only aspect of their chemistry published 33 is their conversion to azines in aqueous acid (Eq. 23).
N_ © 2 3° _ (23)
33 V. Castellana and A. d'Angelo, Atti. R. Acad. Lincei, 14, 145 (1905). CHAPTER XI. RESULTS AND DISCUSSION
A study "has been initiated of the chemistry and synthetic utility of 3-diazo-2, 5-diphenylpyrrole (1^) . Of 29 the known 2- and 3-diazopyrroles, was chosen becauseecaus< 13/ 34 of its intrinsic interest and ease of preparation
(Scheme I) and because it is a safe, brownish-red
0 Scheme I II C,H_-C H „ Q 0 O 6 5 v y Na2S 20 4 || || ^ f > C,H-C-CH0-CH-C-C,Hc. H 20,C2H 50H 6 5 2 2 6 5 II o o O
NO NH4OAc 1) NaOC2H5______
H0Ao c . X V b , 2) (ch3)2chch2ch2ono 6 5 6 5 6 5AJK- ^ b. 5
24
Raney Ni/H2 1) NaNO,/HCl [[K > 2) NaCO C6H5' ^ N ^ = 6H 5
34C.G. Overberger, M. Valentine and J.P. Anselme, J. Am. Chem. Soc., 91, 687 (1969).
19 20
crystalline compound that can be handled easily. In contrast, 2-diazo-3,5-diphenylpyrrole is not as stable as 14 1 and its synthesis proceeds in very low yield.
As pointed out in the Introduction, loss of nitrogen from 1_ can lead to 2, 5-diphenyl-3H— pyrrolylidene (2), possibly a highly delocalized carbene (<2s) in which there is 6 electron (aromatic) stabilization of the pyrrole ring (Eq. 24). A singlet carbene such as 2 - 2s should be
(24) C6H5 * 6 5 c 6h 5 tr c 6h 5 c 6h 5 ^ c 6h 5 1 2 2s highly electrophilic and is expected to insert into C-H bonds, add to olefins to give cyclopropanes and substitute various aromatic substrates. To understand the nature of 2, an investigation of the reactions of 1 with varied substrates was initiated. Photolysis of diazopyrrole 1 in cyclohexane results in 3-cyclohexyl-2,5-diphenylpyrrole (25, 32%) and 2,5- diphenylpyrrole (24, 25%) (Eq. 25) . The structure of 2J5 is established from its elemental analysis and its spectral properties; 2 4 was identified by comparison of 21
(25)
H 1 25 24 its spectra with that of an authentic sample. Careful search of the reaction mixture reveals no other isolable products. Two of the possible attractive explanations for formation of j24 and 2J5 are as follows. Pyrrolylidene 2 is initially generated in the singlet state from 1^ If the carbene has a triplet state close in energy to its singlet state, then intersystem crossing to triplet 2t is highly probable. Such singlet to triplet intersystem crossings are well established, especially for diaryl 35 carbenes. Abstraction of hydrogen from cyclohexane by triplet 2Jt followed by recombination of the cyclohexyl and pyrrolyl radicals (26) can account for 25 (Eq. 26) after hydrogen migration. Pyrrolyl radical _26 should be highly stabilized by delocalization of its unpaired electron through the pyrrole and phenyl rings. Reduction product
24 can arise from 26 by hydrogen abstraction from cyclo hexane and/or cyclohexyl radical.
35 G.L. Closs, in "Topics in Stereochemistry," Vol. 3, E.L. Eliel and N.L. Allinger, Eds., John Wiley, New York, 1968, pp. 198-20 3. 22
11
C,H^SN^'c,Hr ■,k G ^ c 66» 5 Q C 6H : 2t I (26) 0 “ O i ■v
s^. c n r / r h c h *" CcH c 6 5 h C6H5 6 5 6 5
24 25
Alternatively, 2^ may exist as a mixture of singlet
(2s) and triplet (2jt) carbenes. Formation of ,25 can then be explained by concerted insertion of singlet 2s^ into a C-H bond of cyclohexane and triplet 2t may give 24 by the abstraction mechanism discussed earlier. Thermal decomposition of 1^ in cyclohexane also gives 25^ (21.6%) and 24 (16%). A probable reason for the low yields of 24 and 25 is that subsequent reactions involving inter mediates like 2 and 26 destroy the primary products 24 and 2J5. Since the ratios of £5 to 24^ are similar in the photolytic (1.28) and thermal processes (1.35), it is likely that both systems have correnon mechanistic paths, although, based on the above data, clear delineation between the various mechanisms is not possible. 23
To obtain more information as to the properties of carbene 2, cumene was investigated because it is a good hydrogen atom donor to radicals and cumyl radicals 36 dimerize in solution. Formation of 2,3-dimethyl-2, 3- diphenylbutane will therefore be strong evidence for generation of cumyl radicals by hydrogen abstraction by triplet 2t.
Photolysis of !L in cumene at room temperature proceeds smoothly (Eq. 27) to give 2,3-dimethyl-2, 3-diphenylbutane
{27, 25%), 3-(1—methyl-1-phenylethyl)-2,5-diphenylpyrrole
(28/ 43%) and 2,5-diphenylpyrrole (24/ 46%). Similarly, thermolysis of 1 in cumene yields 2J7 (23%), 28 (44%), and
24 (47%). Products 24 and 27_ are identified by comparison of physical constants and spectral data with those of authentic samples and the structure of 28 established by analytical and spectral methods.
hv or A + c 6h 5c h (c h 3)2 -N 2
—1 r*» tr iTTt 27 (27)
H H 28 24 36 R.L. Dannley and B. Zarensky, J. Am. Chem. Soc., 77 1588 (1955). 24
Formation of 27 is indicative of involvement of
triplet 2t_ as a reaction intermediate. However, it cannot be concluded that 2 reacts totally as triplet 2t, because
28 is also concurrently produced, possibly from singlet
2js. If singlet 2!3 and triplet 2t are in equilibrium, then
28 can be formed by direct insertion of singlet 2s^ into the tertiary C-H bond of cumene, followed by hydrogen migration. Alternatively, abstraction of hydrogen from cumene by triplet 2t leads to pyrrolyl radical 26 (Eq. 28).
2t + C6H 5CH(CH3)2 + c 6h 52(c h 3)2
26 (28) H H C6H 5C(CH3>2 — > 24 C6H E
CH~ CH 2C6H 5C(CH3)2
27
Thus, combination of 2J5 with the cumyl radical followed by hydrogen migration gives 28. Dimerization of cumyl radical 25 explains formation of 2^7 and hydrogen abstraction by 26 accounts for 2j4. Thus 24/ 27/ and 28 can possibly all be formed from triplet 2t.
Since the singlet and triplet behaviour of 2 could not be delineated in the reactions with cyclohexane and cumene/ attention was next focussed on olefinic substrates.
Depending on their spin states, carbenes add to olefins stereospecifically (singlet) and non-stereospecifically 37 (triplet). Study of possible addition of 2 to various olefins was then initiated.
Irradiation of 1^ in cyclohexene affords 3-(3-cyclo- hexenyl)-2, 5-diphenylpyrrole (29, 33%) and 2,5-diphenyl pyrrole (24, 21%) (Eq. 29).
,, o * JC\ (29) -N 2 C 6H 5 S 6 5 C6H 5 g C 6H 5 29 24
The identity of 2ji is established by spectral comparison with an authentic sample; 29, however, could not be 38 purified satisfactorily. The gross structure of 29 is
37 W. Kirmse, "Carbene Chemistry," Academic Press, New York, 1971, Chapter 8.
38:A similar difficulty has been reported in analyzing insertion products from 5-diazo-l,2,3-triphenyl- cyclopentadiene and olefins. H. Durr and L. Schrader, Chem. Ber., 102, 2026 (1969). 26
confirmed, however, by its catalytic hydrogenation to the known 3-cyclohexyl-2, 5-diphenylpyrrole (25) . That 2J9 is
indeed the product of allylic insertion is clearly evident
from the NMR signal (6 3.35-3.80) of the allylic hydrogen
of the cyclohexenyl group attached to the pyrrole ring.
Homoallylic insertion to give 29a would not have shifted
the NMR of the allylic-H so far downfield. Thermolysis of
1 in cyclohexene also gives 29 (27%) and 2 4 (24%).
6 5 H 6 5 29a Formation of 29^ and 24 in reaction of 1 and cyclo hexene again leads to the same question: Is 2_ reacting as
a mixture of singlet and triplet states or totally through its triplet state? Product 2J3 can arise by direct insertion of singlet 2s into the allylic C-H bond of cyclohexene.
And, as usual, triplet 2t can account for 24, through two
successive hydrogen abstractions involving pyrrolyl radical
26. Cyclohexene is a hydrogen donor in carbenic decom- positions of o-diazoacetophenone 39 and 9-diazofluorene. 40
D.O. Cowan, M.M. Couch, K.R. Kopecky and G.S. Hammond, J. Orq. Chem., 29, 1922 (1964). 40 J.E. Baldwin and A.H. Andrist, Chem. Comm., 1512 (1971) 27
A second alternative is that 29 and 24 are formed from triplet 2t as in Eq. 30. Indeed, the "insertion product" 3-(91-fluorenyl)cyclohexene from photolysis of
9-diazofluorene in cyclohexene is produced by hydrogen 40 abstraction followed by radical recombination; similar 41 reactions of phenylcarbene occur in frozen olefin matrices. Such a mechanism {Eq. 30) is similar to those
2 t + n i - > A A + (I J A — C6H5 N C6H5 C6H 5 N C6H 5 26
J, Q o r 0)
(30) 24
discussed for reactions of 1^ with cyclohexane and cumene. 39 40 Radical abstraction reactions involving cyclohexene ' are known to produce 3, 3'-bicyclohexenyl (30); no 30 was found, however, from reaction of 1 in cyclohexene.
30 41 R.A. Moss and U.H. Dolling, J. Am. Chem. Soc., 93, 954 (1971). — 28
Of note is that spiro adduct 3J. was not found in photolysis or thermolysis of 1 in cyclohexene. It is possible that 31 isomerizes to 29 via 32. If that were so,
H 6 31 it is expected that _32 would also give 3-{1-cyclohexenyl)-
2,5-diphenylpyrrole (_33) (Eq. 31). Since 32 was not found, there is strong reason to believe that addition of 2 to the double bond of cyclohexene does not occur.
_ j 0
29 29
To clarify whether the apparent insertion product 29 might be formed by abstraction-recombination, the reactions of 1 with 2,3-dimethyl-2-butene were investigated.
Abstraction of primary hydrogen from the olefin by triplet
2t would give unsymmetrical radical 34- 35. Photolysis of
CH-- CH. CH. . CH. > = < > —< ; c h 2 ch3 h 2c ch:
34 35 phenyldiazomethane in frozen cis-2-butene matrix has been previously shown to give 36-37 which combined at its
• CH- CH- CH- CH_ 3 2 ^ / 3
36 37 primary or secondary positions with the benzyl radical 41 generated. Such a recombination of pyrrolyl radical 26 with 3 4 - J3!5 would then give two isomeric products indicative of abstraction-recombination in the present system.
In any event, photolysis of 1 in 2,3-dimethyl-2- butene affords only one isolable product, 3-(2,3-dimethyl-
2-butenyl)-2,5-diphenylpyrrole (38, 39%) (Eq. 32) identified by elemental analysis and spectral data. A NMR 30
(32)
38
signal at 6 3.42 and the absence of any olefinic proton
signals and IR bands for olefinic C-H bonds all point to
structure 38. The absence of 2/5-diphenylpyrrole (24)
comes as a surprise but this fact is not strong enough evidence to demand intervention of singlet 2£ . Formation of 38 may occur from triplet 2t by hydrogen abstraction followed by recombination through a tight or sterically discriminating radical pair. A likely reason for the
failure to see any 3-[3-(2, 3-dimethyl-1-butenyl)]-2, 5- diphenylpyrrole (38a) is because of steric crowding around
H
38a the tertiary radical center in 34-_3!5 making recombination with 26 unfeasible.
Study was next extended to allylbenzene. If there were hydrogen abstraction from allylbenzene, then radical 39 - 40 would be formed. In radical combination with 39 -
40, reaction is expected to favor 40 because of extended
conjugation and steric accessibility in the transition
state leading to product.
C WCH-CH=CH„ < — 5- C H -CH=CH-CH . D O Z O D Z
39 40
Photolysis of diazopyrrole 1 proceeds readily in
allylbenzene to give three i sol able products: pyrrole 2j4
(25%), readily identified by spectral analysis (and
frequency of its occurrence!) and an inseparable mixture of 2, 5-diphenyl-3- (1-phenyl-2-propenyl)pyrrole (41^) and
2,5-diphenyl-3-(3-phenyl-2-propenyl)pyrrole (42/ 32%).
Thermolysis of 1 in allylbenzene yields the same three products, 2j4 (31%), 41^ and 4,2 (33%). Since the IR and NMR of the mixture are not very informative, chemical methods were used to identify the components. Mass spectral
analysis shows a peak at m/e = 335, which corresponds to molecular ions of 41^ and 4^2. Catalytic hydrogenation of the mixture over palladium/carbon simplifies the NMR
spectrum considerably. The olefinic proton resonances in the NMR are now replaced by signals at higher fields and 32 the absorptions of the aliphatic protons of the reduced mixture are similar to those of 1,3-diphenylpropane and
1,1—diphenylpropane in admixture. Thus the distorted triplet at 6 0.90 is that of a methyl group, which, prior to reduction, was the terminal methylene of 4jL. Again, a distorted quartet at 6 2.62 representing the ' s flanked by phenyl and pyrrole rings, are derived from the carbons underlined in 42 (Eq. 33). In order to establish the
41 (33)
6 5 6 5
42 24 position of the double bond in 4J2 unambiguously, an oxidative degradation of the mixture of 41 and 4J2 was effected with osmium tetroxide/potassium periodate to give benzaldehyde as the only volatile product detectable by
GC. Since phenylacetaldehyde could not be found, the structure of 42, including the position of its double bond, is confirmed. 33
Formation of 24, 41 and A2_ is readily explained via
triplet 2t. Thus, abstraction of the allylic hydrogen from
allylbenzene (Eq. 34) produces 26 and 39 - 40, recombination
hv or & + C,HcCH-CH=CH_ O O Z. £ N' ' r H C 6 5 C6H 5 6 5 6 2t \ 26 + C6H5CHCH=CH2CH< (34)
39
C6H5CHCH=CH2 < — > C6H5CH=CH-CH21
39 | 40 I
~ \ ~ C6H 5 H H NCHCH=CH2 CH„CH=CH-C/-H
C,H_AX. N C,H_ H 6 5 6 5 6
CfiHR \D 3 CH-CH=CH-CaH (- HC*CH=CH / *
C,H, N C-H_ C£H c £ 6 5 o 5 jj 65 6 5 11 41 42 of which with 26 at isomeric allyl positions with
concurrent hydrogen migration accounts for 41 and 42.
Reaction of 1^ with allylbenzene therefore clearly
demonstrates that the predominant, if not the exclusive
path of reaction of 2 is through triplet 2t.
The behaviour of 2 discussed so far seems to indicate
that it reacts as a triplet (2t) or as an equilibrium
mixture of singlet (2s)and triplet (2t). Depending on the
substrate used for interception of 2, the possibility
exists that the equilibrium can be shifted towards either
spin state. Since singlet 2js is expected to be electro- philic, it is quite likely that by intercepting 2 with
substrates which are strongly nucleophilic such as
alcohols, ethers or amines, enhanced singlet behaviour will be observed. To test this hypothesis, decomposition of 1 was effected in a variety of nucleophilic media.
Photolysis of 1 in methanol gives 2,5-diphenylpyrrole
(24, 27%) and 3-methoxy-2,5-diphenylpyrrole (43, 12%) along with intractables. Products 24 and £3 are assigned
from their analytical and spectral data (Eq. 35). Since
(35) 34 of which with 26 at isomeric allyl positions with concurrent hydrogen migration accounts for 41 and 42.
Reaction of 1 with allylbenzene therefore clearly demonstrates that the predominant, if not the exclusive path of reaction of 2 is through triplet 2t.
The behaviour of 2 discussed so far seems to indicate that it reacts as a triplet (2t) or as an equilibrium mixture of singlet (2s)and triplet (2t). Depending on the substrate used for interception of 2, the possibility exists that the equilibrium can be shifted towards either spin state. Since singlet 2s is expected to be electro- phi lie, it is quite likely that by intercepting 2 with substrates which are strongly nucleophilic such as alcohols, ethers or amines, enhanced singlet behaviour will be observed. To test this hypothesis, decomposition of 1 was effected in a variety of nucleophilic media.
Photolysis of 1 in methanol gives 2,5-diphenylpyrrole
(24, 27%) and 3-methoxy-2,5-diphenylpyrrole (43, 12%) along with intractables. Products 2j4 and £3 are assigned from their analytical and spectral data (Eq. 35). Since
(35)
6 5 24 43 35 the fate of methanol (presumably formaldehyde is formed) in these experiments cannot be easily ascertained, photolytic decompositions of 1 were effected in 2-propanol.
Decomposition of 1 proceeds readily, affording 2£ (67%) along with acetone (6 4%) as determined by GC using an internal standard. That alcohols are oxidized to the corresponding carbonyl compounds is further confirmed by thermolyzing 1 in benzyl alcohol and isolating benzalde- hyde as its 2,4-dinitrophenylhydrazone (65%) along with
24 (70%). Thermolysis of 1 is very slow in 2-propanol
(100- hrs at 80°) yielding .24 (59%) ; 1 does not react with refluxing methanol even after 1 weeX. Photolytic reaction of 1 with methanol is about 6 times slower than with
2-propanol.
These results imply that more than one mechanism operates in reactions of 1 with alcohols. Photolysis of
1 in 2-propanol can be explained on the basis of triplet
2t (Eq. 36). Abstraction of the methine hydrogen by 2t leads to the pyrrolyl radical 2j5 and the 2-hydroxy-2- propyl radical 44. Further reaction as shown (Eq. 36) accounts for 24 and acetone. Similar mechanisms for reactions of 1 with methanol and benzyl alcohol account for
24 along with formaldehyde and benzaldehyde, respectively. 36
if JL^ ^ + (ch3)2choh => C6H5 N C6H5 6H 5 6 5 2t 26 (36) » H OH ^--V + CH- - C - CH. >- A + CH-COCH- 6 ' J C-Hc' XX N C,H_" "„ ♦ 6 5 6 5 44 I
CcH(-XX „ C-Hj- 6 5 H 6 5 24
It is not possible/ however, to accommodate formation of methoxy ether 43 in the above mechanistic scheme.
Production of £3 presumes intervention of singlet £s possibly via the mechanisms of Eq. 37. The first proposal
CH -H H
'6 H5 & S
6 5 J 6 5 43
(37»
C6H5 " ~6 "5 37
envisages betaine formation between the electrophilic carbenic center and the nucleophilic oxygen atom of the alcohol followed by hydrogen migration to form £3. It is well known that diazodiphenylmethane in alcohols converts 42 to ethers by the betaine mechanism of Eq. 37. An alternate pathway involves reaction of methanol as an acid to give cation 45, which is converted by methanol and/or methoxide, to £3. A third mechanism may be considered for formation of
43 (Eq. 38) . In this case methanol protonates diazopyrrole © NSN © + OCH 3 H 1 3 (38)
H 43
1 to diazonium ion .3 which then reacts with methanol and/or methoxide with loss of nitrogen to form 43. This mechanism seems unlikely since diazopyrrole 1 is recovered almost
42 D. Bethell, A.R. Newall, G. Stevens, and D. Whittaker, J. Chem. Soc. B, 749 (1969). 38
quantitatively from refluxing methanol after 1 week.
Another possibility is that the excited state basicity of
1^ is greater than its ground state basicity, thus leading
into the sequence of Equation 38. Significant differences
in acidity and basicity between ground and excited states 43 are known. Whether such effects operate in the present
example is unclear.
The rate difference in photolysis of 1 in methanol and
2-propanol is probably due to some kind of difference in
solvent stabilization of 1 by methanol relative to 2- propanol, thus retarding loss of nitrogen. Such effects have been observed in thermal decompositions of 3-diazo- pyrazoles in methanol and in 2-propanol. 25
One possible way by which the cationic process in
Equation 38 can be made to predominate is to generate
appreciable concentrations of diazonium ion 3 by adding
acid to 1^. To test this hypothesis, photolyses of 1 were carried out in methanol and 2-propanol in the presence of
50% excess trifluoroacetic acid. This acid was chosen because it is very strong but yet has no abstractable hydrogen atoms which might complicate the reactions. In
any event, irradiation of 1 in methanol and in 2-propanol
43 J.F. Ireland and P.A.H. Wyatt, in "Advances in Physical Organic Chemistry," Vol. 12, v. Gold and D. Bethell, Eds., Academic Press, New York, 1976, pp. 132- 221. 39
in trifluoroacetic acid gives the results summarized in
Equation 39. 2,5-Diphenyl-3-(2-propoxy)pyrrole (46) is
N 2 ^ o r r, CF-CO-H
AJ k ' “ “ - t * * X X . * C6H5 °6H5 C6 5 H C6H5 1 24 R = CH3 11% 44% 43
R = (CH3)2CH- 31% 24% 46
identified by the distinct NMR and IR features of its
isopropyl group as well as by its mass spectral and
elemental analyses. Photolytic decomposition of aryl diazonium ions in 44 45 hydroxylic media has had a long history. ' Calvert and 44 co-workers In an investigation of photolyses of m- and p- nitrobenzenediazonium salts in ethanol (Eq. 40) suggest
that two mechanisms operate. All products except
p-nitrophenetole are explained by a radical mechanism.
The first step in such a process is decomposition of the
44 W.E. Lee, J.G. Calvert and E.W. Malmberg, J . Am. Chem. Soc., 83, 1928 (1961).
45E.S. Lewis, R.E. Holliday and L.D. Hartung, J. Am. Chem. Soc., 91, 430 (1969). n o 2 o c 2h 5
°2N“(0)-N2 X + C2H5OH ~5°~^ IQJ + (OJ + CHjCHO n o 2
76.6% 5.4% 74.1% NO 2 (40) + CH3-CHOH-CHOH-CH3 + IQ ] r o
1-54% CH.CH-OH f°H CH3 2 *3% 3.6% of the diazonium salt to p-nitrophenyl radicals which
subsequently convert to products (Eq. 41) by hydrogen
abstraction and radical combination reactions.
n ° 2 n o 2
hV fOl O J ------> I w J + N 2 + X* © Q n 2 X (41)
V - ® - + CH3CH2OH > 02N + CH3CHOH
c h 3c h 2o h > o 2n + *c h 2c h 2o :
CHOH °2N - < © > - + CH3^HOH ---^ °2N -<0)- t CH3
° 2n * + *c h 2c h 2o h ----> c h 2c h 2o h 2 CH3CHOH > CH3CH0 + CH3CH2OH On the other hand, a cationic intermediate is postulated in formation of p-nitrophenetole (Eq. 42).
That the ether is not formed by radical recombination
©
(42)
— > °2N^ § ) - OC2H5 receives support from the observation that when photolysis is conducted in the presence of iodine, the yield of ether is not significantly diminished which would be the case if radical intermediates were involved in its formation.
Iodine greatly reduces the conversion to nitrobenzene and a new product, p-nitroiodobenzene is formed. This is good evidence that nitrobenzene originates from a radical source since iodine is a good radical trap. Lewis, Holliday and Hartung 45 in investigating the photolysis of aryl diazonium salts in aqueous sodium chloride find that the amount of the appropriate chloro- benzene formed (Eq. 43) is different than for thermal processes. On that basis, they argue that the thermal and 42
X-<@>-N2 Cl° + aq. NaCl — >X-^Q^-OH + X ^ Q ^ C l (43) photochemical decompositions do not have a common mechanism and propose an "unidentified" excited state as the reactive intermediate in photolysis.
Heterocyclic diazonium salts have also been decomposed photolytically. 46 ' 47 Thus, irradiation of 2- and 4- imidazolediazonium tetrafluoroborates in aqueous tetra- fluoroboric acid afford the corresponding fluorides in
30- 40% yields (Eq. 44). However, there is no discussion
50% HBF4 [H ------> Nv .NH 'Y 7 '© © 1 N,TBF, F n2 4 30% (44) © 0 N 2 BF4 - F / = { 50% HBF / \ NH ------— > N . NH ^ hv ^ 41% of any mechanistic details in the publications as the researches were more concerned with preparative than mechanistic aspects.
K.L. KirX and L.A. Cohen, J. Am. Chem. Soc., 95, 4619 (1973). 47 K.L. Kirk, W. Nagai and L.A. Cohen, J. Am. Chem. Soc., 95, 8389 (1973). 43
As has been summarized earlier, photolysis of diazopyrrole 1 in methanol gives 3-methoxy-2,5-diphenyl- pyrrole (43) and 2,5-diphenylpyrrole (24) in the ratio
4:9; photolysis in the presence of acid changes the ratio to 4:1. In 2-propanol, neutral photolysis produces no ether at all; in presence of acid, however, the ratio of
2,5-diphenyl-3-(2-propoxy)pyrrole (46) to 2,5-diphenyl- pyrrole (Z4) is — 3:4.
More than one mechanistic explanation rationalize the products of the present study. The most straight forward rationalization is that diazonium ion 3^ during photolysis loses nitrogen to give radical 47 and cation
48. Another source of radical 41_ is photolytic decom position of azoether 49, formed by capture of .3 by alcohol. All these are shown in Equation 45. Abstraction of hydrogen atoms from the alcohol accounts for pyrrole
24 and capture of the solvent by cation 48 followed by proton loss gives ether 43^ A similar mechanism can be proposed for ,3 with 2-propanol, except that it is not clear why the ratio of ether 46 to pyrrole 2j4 is so low, especially if initial decomposition of diazonium ion does not involve the solvent. However, diazonium ion 3 might 44
e @ O — R hv f l Ron -N . - a . C H C6 C6H5 S C6H5 -X 3 45
►OR - H ®
C,H-xl N C,Hc & D jj u O
43 R = CH,
46 R = 2-C3H7 ©
hV -> H 6H 5 ’” 2 CcH cxx fi C 6H 6 5 6 5 47
N=N-OR — RO. i ~ \ + roh — ) j ~ \ > r ~ \ + C6H5 « C6H5 C6H5 g C6H5 “"2 c6V^g V s 49 47 R = CH3 or 2-C3H?
-[ROO + ROH X‘N’1 XkN °6H 5 H C6H 5 C6H 5 H C6H 5
47 24 45
be solvated by alcohols and thus the degree of solvation
is responsible for the different product ratios. Photolysis of 1 in diethyl ether affords only one
isolable product, 2,5-diphenylpyrrole (2 4) in 8% yield
(Eq. 46). This result is quite surprising, since
jrK + C2H 5OC2H5 (46) C e C * c 6h 5 ce«5 « c 6h 5 1 24 diazocyclopentadiene 48 results in insertion of cyclopenta- dienylidene into the a- and£- C-H bonds of diethyl ether in the ratio of 23:1 (Eq. 47) and 3-diazo-5-phenylpyrazole
CH~CHOC_H CH_CH_OC_H
+ c 2h 5o c 2h 5 (47)
23 1
(17) photolyses in diethyl ether to yield 5-ethoxy-1-ethyl- 3-phenylpyrazole and 3-ethoxy-l-ethyl-5-phenylpyrazole in
3:2 ratio by cleavage of the oxygen-ethyl bond 25 (Eq. 48).
It may be that products of insertion from the present
48 J.E. Basinslci, Ph.D. Thesis, Yale University, New Haven, Conn., 1961. 46
(48)
3 2 system such as 50 react further to give the intractables obtained. A likely path to 2 4 is abstraction of a-H of
CH3CHOC2H 5
6 5 H 50 diethyl ether by 2Jt to form radical 2£ which then abstracts additional hydrogen from the environment (ether, products and radical intermediates# etc.). In view of the success in synthesizing ethers by irradiation of 1 in alcohols in the presence of acid# photolysis of 1 in glacial acetic acid was investigated to see if a product of O-H insertion into acetic acid could be isolated. Photolysis of 1 in glacial acetic acid is 47
found to give 2,5-diphenylpyrrole (24, 7.3%) and 3-acetoxy- 2,5-diphenylpyrrole (51, 20.2%) respectively (Eq. 49). xji ^ C.H. C,H 2 C H £ C,H 6 5 , 65 OCOCH, 6 5 65 S 24 (49)
* C6H5 r 6 5 51
Mechanistically, reaction of 1 with acetic acid is probably similar to that with alcohols in the presence of
acid. Thus, acetic acid can protonate 1 to 3 and then photolysis gives cation 48 which is captured by acetic
acid and/or acetate ion (Eq. 50). Pyrrole 24 can be
©
J i~ \ + c h 3c o o h > oC6H w 5 N C*H 6 5*; c 6 H 5 Hn ^ C 6 H 5 1 3 (50) ^ ® CH3C00B OCCH
-N„ r d H or CH COO© 2 6 5 H 6 5 3
48 51 48 obtained by homolytic cleavage of the pyrrole azoacetate
52 or diazonium ion 3 to radical £7 followed by hydrogen abstraction (Eq. 51).
N ® X ©
C-H IX C6H5 H C6H5
2 & f (51) N = N-OCCH. 3 hv CH^COO.
C IX ”2' 6 6H 5 C6H5 H C6H5 62 47
JT\ -™ .3— - p . + CH COO- C6H5^/^C6H5 C6H5 H C6»5
47 24
Recently/ there has been interest in conversions of heterocyclic diazo compounds and secondary amines to triazenes which are of value in treatment of tumours.^' ^
(Eq. 52). Heterocyclic amines such as pyridine are also known to react with diazocyclopentadiene with loss of
49 h *Y.F. Shealy and C.A. O'Dell, J. Phar. Sci., 60, 554 (1971) 49
II N=N-N=N-N(CH3) R X -/2 * ' / = ( N'v NH JQ * lce>)* a
R = OCH_, OC„Hc (52) 6 Z D and NH„
_N=N-N I
■> Q i-C4H9 H 21
50 nitrogen to form stable ylids (Eq. 53). Since 2 as 2js is expected to be an excellent acceptor of nucleophiles/
H C 5 6 o -N. Cy- H C it was of interest to determine if reactions of j2s with tertiary amines would give analogous ylids. Investigations of the reactions of 1^ with diethylamine and triethylamine were thus initiated.
50 I.B.M. Band, D. Lloyd, M.I.C. Singer and F.I. Wasson, Chem. Comm., 544 (1966). 50
Photolyses of 1 in diethylamine and in triethylamine give only one isolable product/ namely 2,5-diphenylpyrrole
(24) in 74 and 60% yields respectively. Reduction of 2 to
24 by such amines is quite surprising; there was no evidence for 53 and 54 in these experiments. The overall © N(C2H5)3
53 54 reactions can be represented in Eq. 54. The behaviour of
1 with diethylamine and triethylamine thus parallels that
(54)
6 5 1 24 with diethyl ether. It may be presumed that 24 is formed from 2t by successive hydrogen abstractions from a-C-H and/or N-H positions of the amines. The fact that reduction rather than ylid formation occurs in these systems is impressive. 51
The reactions of 1 described thus far appear best
interpreted in terms of an equilibrium between the singlet
(2s) and triplet (2t) states of 2, in which the singlet inserts into C-H bonds and the triplet effects hydrogen abstraction with subsequent recombination and/or reduction.
To clarify further the behaviour of 1, a study of its reactions with aromatic substrates was envisaged. Since it is difficult to abstract hydrogen from benzene derivatives, it was thought that the singlet behaviour of
2 might predominate in such systems. Also, by studying the effects of various substituted benzenes on the reactivity and orientation in substitution, the electrophilic or nucleophilic reactivity of might be better understood.
Photolysis of 1 in benzene affords a bright yellow solid, 1,3-diphenyl-2 H-cycloocta[c]pyrrole (55, 30-32%) along with intractables. No other product (including biphenyl) could be detected. Thermolysis of 1 in refluxing benzene occurs slowly (> 90 hr) to give only 5J5 and recovered
1^ at 175° in an autoclave, reaction is complete in 1 hr and 5J5 is formed in 68-69% yield and again biphenyl is absent (Eq. 55) . Adduct 5J5 analyzes for and exhibits a strong mass spectral peak at m/e = 295. These 52
N 2
hv or a (55) > -N ■N 2 C6H5 H C6H5 X 55
facts indicate that 5J5 is a 1:1 addition product of
carbene 2 and benzene. The NMR spectrum shows sets of peaks in the olefinic (6 5.79 - 6.36) and the aromatic
(6 7.12-7.52) regions integrating in the ratio 3:5, along with a broad downfield signal attributable to hydrogen on pyrrole nitrogen. The CMR spectrum of 5J5 consists of nine lines, consistent with the symmetrical structure assigned. Decoupling shows the presence of four kinds of aromatic carbons (one of them quaternary) and two types of pyrrole carbons, which together account for sixteen of the twenty-two carbons of 5J>. The remaining six carbons are therefore of three different types and are olefinic
(from NMR data). All these facts establish the structure of 5j5. Further, the NMR spectra of the olefinic regions of 55 and cycloocta[c] furan (5j6) 5 X show strong similarities.
51 E. Le Goff and R.B. LaCount, Tet. Letters, 2787 (1965). 53
Expansion of benzene by cyclopentadienylidenes to fused eight membered ring derivatives has been previously reported. Thus, photolyses of diazocyclopentadiene, 5-diazo-l,3-diphenylcyclopentadiene and 5-diazo-l,2,3- triphenylcyclopentadiene in benzene form bicyclo[6.3.0]- undecapentaenes 7 ' 8 {Eq. 56). Thermolysis of 5-t-butyl-
R.
hv R (56) -N, R 1 R 1 = R 2 = H
R 1 = C6H 5' R 2 ~ H
R1 * R2 = C6H5
3-diazopyrazole (£1) in benzene gives 2-t-butylpyrazolo-
[3, 2-a]azocine (5_7) in 5-10% yield along with much 3(5)-t-butyl-5(3)-phenylpyrazole {85-90%)^ (Eq. 57). 54
N C6H 5
+ceH6 ^ t-C^ N t-C4H9 21 85-90%
+ t-C .H,9
57 (5-10%)
Photosensitization of diazo compounds is Tcnown to generate triplet diazo compounds and then triplet carbenes
(Eq. 58). It was of interest to determine the products of photpsensitization of 1 in benzene.
hv * Sensitizer Sensitizer (Excitation) * * Sensitizer 1 --- > Sensitizer 3 (Intersystem crossing) 3* Sensitizer + Diazo compound — > Sensitizer + Diazo 3* (58) compound (Energy Transfer)
Diazo compound^ --- ^ Carbene (^1) + N2
Irradiation of 1 in benzene in the presence of thioxanthen-9-one as sensitizer (ET = 65.5 Xcal mole-^) leads to only one tractable product, 2,3,5-triphenylpyrrole
(16) in 45% yield (Eq. 59). Neither eyeloocta[c]pyrrole 5J5 nor biphenyl is formed. The identity of 16 is established 52 from its reported properties and spectra* Photolysis of 55
C,Hc>cC*<§> C,H,- 6 5 H 6 5 6 5 6 5 16 l59)
1 in benzene using Micbler's ketone as sensitizer (E^ = 61 kcal mole"1) gives a mixture of 2,5-diphenylpyrrole (24) and 2, 3, 5-triphenylpyrrole (lj5) in a ratio of — 1:1
(Eq. 60).
n 2 O j r \ + to) (ch3)2n-^-^-<§)- N(CH3)2
t N y. t t Vl\l . M C6H5 C6H5 hV' -N' (60) 1 C6«5
C6H5 H C6H5 C6H5 H C6H5 24 16
1 : 1
The NMR spectrum of the product reveals doublets at 6 6.55 and 6.66 for 24 and 16, respectively. The IR spectrum of the mixture has bands common to both 1£> and 2^4 and com parison with the spectrum of a 1:1 mixture of 16 and 24
52 F. Angelico and E. Calvello, Gazz. Chim. Ital., 31, II, 4 (1901). 56
shows a 1:1 correspondence. The origin of 3j5 is most likely triplet 2t, but formation of 2j4 comes as a surprise and will be discussed later.
The reactions of 1^, both thermal and photochemical, were then studied with a series of benzenoid substrates.
All products which could be separated were identified completely by spectral methods and elemental analysis and in a few cases, by unambiguous synthesis or by degradation to known compounds. Inseparable mixtures were assigned by various spectroscopic techniques and occasionally by rationalization. Thermolysis or photolysis of 1 in toluene yields a mixture of five products: (a) 1,2-diphenylethane
(58), whose identity is established by NMR and GC; (b) 2,5- diphenylpyrrole (2 4) , and (c) an inseparable mixture of
3-benzyl-2,5-diphenylpyrrole (59), 2,5-diphenyl-3-(p- tolyl)pyrrole (60) and 2,5-diphenyl-3-(o-tolyl)pyrrole (63J in — 1:1:1 ratio (Eq. 61). 57
y,N2 FH 3
+ (O) " N°r & > C6H5CH2CH2C6H5
C,Hc6 5 N C£H 6 5c 2 —58 hv 3-,„ (61) L 2 - 3 % + ,CH2C 6H + 5 XXISO C6H5 H C6H5 C6H5 H C6H5 C6H5 H 24 59 60 and 61
hv 5-6% 34%
A 13-14% 40-41% The presence of 5J9 and 60 is confirmed by synthesis of authentic samples (Schemes II and III) and that of 61 is inferred on the basis of mechanistic reasoning.
Scheme II 1) NaOC H, (C,HcCO) _CH_ ------^ --- => (C-.Hg.CO) _CHCHoC0Cv.Hj. 6 5 2 2 2) C,H(-COCH_Br 6 5 2 2 6 5 6 5 2
NH.OAc He B_H, ?H 2C6H5 4 ^ 5 2 6 - > HO AC, L / \ u THF C 6 C6H 5 H C6H5 59 58
Scheme III
/— \ NaOH ,— w II C H , - / 0 ) - CHO + CH_COC_H, ^ CH,-< O A CH=CHC-ctHe; 3 VV 3 6 5 c„H-0H/H„02..5o h /h 2o 3 NT/ 6 5 62
1) n-BuLi 2) Culcuj. A) /— v || C-.Hj.CH (SC,Hr) „ => CH.-(0)-CH-CH2CcfiHr 6 5 6 5 2 3) 62 in THF 3 V I / I . 2 6 5 c (s c 6h 5 )2
C6H5
cuo/cuci2 r/—\ r \ m|| NHnh„oac OAC CH„-< 0/ - C H - CH„-C-C,H_ ------> H O/acetone 3 V'— I / f ' | 2 6 5 HOAc, A * ° " S 6h 5 CH3 63
c 6 60
The photochemical and thermal reactions of 1 with
anisole are cleaner and give only two products, 2,5-
di phenyl pyrrole (.24) and 3- (p-methoxyphenyl)-2, 5-diphenyl pyrrole (6^4) which are separable by chromatography (Eq. 62) .
The structure of 6_4 is established by spectral methods.
Thus the mass spectrum shows 64 to be a 1:1 addition product 59 OCH:
N„ OCH.
IX*N „* © ^ —N„ „ „IX N „ „ * „ IX.„ N C^Hr C,H, C,Hc 2 C6H5 h C6H 5 C6^ h 6 5 '6“5 6 5 1 24 64
A 15-16% 50% hv 8-9% 42-43%
of 2 and anisole and the IR has a band at 830 cm-'*’, indicative of a p-substituted benzene ring. The
structural assignment is reinforced by NMR signals at 6 3.73 for the methoxy group and part of a AA'BB' pattern
at 6 6.78 for a para-substituted benzene. Synthesis of an
authentic sample by an independent method establishes the
identity of 64 unequivocally (Scheme IV).
Scheme IV O y— y NaOH j— y n CH-,0“\ O / CHO + CH-CO-C,H(------>■ CH_0< O/- c h =c h c c a h r 3 3 6 5 c _h ko h /h _o 3 6 5 Z D Z 65
(I °H 1) NaCN/DMF y—y ° C-C—C,H_ ------> CH_0 “\ O / CH-CH--C-C-H 6 5 H 6 5 2) ^ /DMF 3 0 = C 2 6 5 OCH„ °6H5 66
NH.OAc 4 > HOAc, A H H "6"5
64 60
The reactions take a totally different course with benzonitrile. Thermolysis or photolysis of 1 in benzo- nitrile results in cyano-1,3-diphenyl— 2H-cyclooctarc]- pyrroles (67/ 68 and 69) (Eq. 63). Elemental analysis and mass spectral data help establish the molecular CN
N 2 CN hv or A (63) -N 2 C6H5 C6H5
6J7, 68, and 69
hv 35 - 36% A 46 - 47% formula of the product as C23**16N2' a adduct of 2 and benzonitrile. The IR spectrum shows a band at 2220 cm“^ for a cyano group. An olefinic NMR multiplet is displayed at 6 5.50- 6.88 and the ratio of the olefinic to aromatic protons is ~ 1:2, thus revealing the presence of five olefinic protons and the cycloocta[c]pyrrole 13 structure. The C NMR spectrum has signals at 118.12,
117.25, and 116.61 ppm (TMS = 0 ppm), thereby indicating the presence of three different cyano groups. This is possible only if the product is a mixture of three 61
compounds, 4-,5- and 6-cyano-l, 3-diphenyl-2 H-cycloocta-
[c]pyrroles (67, 68, and 69), respectively. The composi tion of the mixture could not be determined. Photosensitized decomposition of 1 in benzonitrile using thioxanthen-9-one as sensitizer gives an entirely different product assigned as 3-(o-cyanophenyl)-2,5- diphenylpyrrole (70) in 19% yield (Eq. 64). The mass
O
1
spectrum of 70_ shows it to be a 1;1 adduct of 2^ and benzonitrile and a cyano group is revealed by the IR band at 2230 cm "L. The NMR spectrum, however, has no olefinic signals but displays a doublet at 5 6.70 for a hydrogen on the carbon of the pyrrole ring, suggesting insertion of 2_ into one of the C-H bonds of benzonitrile. The exact position of the cyano group of 7£ cannot be determined by spectral methods and is presumed upon comparison to independently synthesized samples of _3-(p-cyanophenyl) -
2/5-diphenylpyrrole (Tl) and 3-(m-cyanophenyl)-2, 5- diphenylpyrrole (7j?) {Schemes V and VI, respectively).
Since 70 is different from 71 and 72, it is assigned as
3-(o-cyanophenyl)-2,5-diphenylpyrrole.
Scheme V
NaOH
73 1) n-BuLi O 2) Cul C6H 5CH(SC6H 5)2 3) 73 in THF
o CuO/CuCl2 tl NH.OAc CH-CH_-C-C,Hc 4 I^O/acetoneT NC- < o > ^I 2 6 5 HO Ac, L o ^ c 6h 5 63 Scheme VI o II _ Na0H / r \ CH=CHC-C6H5
1) n-BuLi 0 2) Cul C£H cCH(SC£H,.) „ CH - CH0-C-CfcH 6 5 6 5 2 „c _ t1T
C6H5 H
Diazopyrrole 1 when thermolysed in nitrobenzene affords a mixture of four products: (a) 3-(m-nitrophenyl)-
2,5-diphenylpyrrole (77, 9-10%); (b) an inseparable mixture of unknown composition of 4- and 6-nitro-l,3- diphenyl —2 H-cycloocta[c]pyrroles (78 and 7£, respectively, 64
13-14%); and (c) 5-nitro-l,3-diphenyl— 2 H-cycloocta[c]- pyrrole (80, 17-18%) (Eq. 65). Mass spectrally, all
1 6 5 H 77 NO 5 (65)
78 79 80 products correspond to 1:1 adducts of 2 and nitrobenzene.
The NMR spectrum of T7 reveals no olefinic protons and a doublet at 6 6.92 indicative of a hydrogen on carbon of the pyrrole ring. A likely structure for T7 is a product arising by insertion of 2^ into one of the C-H bonds of nitrobenzene. To locate the nitro group on its phenyl ring, T7 was oxidatively degraded using potassium permanganate. Esterification of the carboxylic acid product with diazomethane and analysis of the esters by
GC reveals the presence of methyl benzoate and methyl 65
m-nitrobenzoate. Detection of methyl m-nitrobenzoate confirms the structure of 11_ as 3-(m-nitrophenyl)-2,5- diphenylpyrrole. The NMR spectrum of 7jB and 79 has
signals in the olefinic region, but none characteristic of hydrogen on carbon of the pyrrole ring. The absence of hydrogen on carbon of the pyrrole ring is good evidence for a cycloocta[c]pyrrole framework. On the basis of the structure assigned to 8£ (see below), 78 and 79 are formulated as 4- and 6-nitro-l,3-diphenyl — 2H-cycloocta-
[c]pyrroles respectively. The NMR spectrum of 80 also displays olefinic proton signals, suggesting similar structural features as 78 and 79^ and a sharp singlet at
6 7.85 which is not due to an aromatic proton (aromatic protons appear at 5 7.03-7.67). The singlet comes from one of the olefinic protons, most lihely the one underlined in 80. This conclusion is supported by the NMR spectrum 66
of 4-nitrobenzocyclooctatetraene (81) in which a singlet signal at 6 8.03 is assigned to proton H 53. Also A protons at positions 3 and 5 in benzocyclooctatetraene 53 (82) are not coupled Therefore, 80 is designated as
5-nitro-l,3-diphenyl — 2 H~cycloocta[c]pyrrole.
Photolysis of 1^ in a, at, a-trif luorotoluene presumably gives an inseparable mixture of 2,5-diphenyl-3- (trif luoromethyl- phenyl) pyrroles (83/ 84, and 85) and trif luoromethyl-1, 3- diphenyl— 2H-cycloocta[c]pyrroles (86, 87, and 88) as summarized in Eq. 66. The mass spectrum of the mixture
83, 84, and 85
CF + 3 (6 6)
86, 87 and 88
53 J.A. Elix and M.V. Sargent, J. Am. Chem. Soc., 91 4734 (1969). 67
has a peak at m/e = 363, corresponding to a 1:1 adduct of
2 and a, a, ey-trifluorotoluene. The NMR spectrum of the product displays a multiplet at 6 5.83-6.67 for olefinic
and pyrrole hydrogens on carbon. On shaking a chloroform-d
solution of the mixture with deuterium oxide and potassium
carbonate one of the NMR doublets at 6 6.6 4 collapses to a
singlet, indicating a loss of coupling when N-H is con verted to N-D. Since a hydrogen on carbon of the pyrrole
ring is coupled to hydrogen on the pyrrole nitrogen, the
loss of coupling in the exchange experiment establishes the presence of product(s) having hydrogen on carbon of the pyrrole ring, namely 2, 5-diphenyl-3-(trifluoromethylphenyl)- pyrroles, although the position(s) of the trifluoromethy1 group on the phenyl ring is(are) not known. Also, the
relative proportions of aromatic substitution and ring
expansion could not be determined.
The specific reactions of 1 with benzene and its
derivatives are identical thermally and photochemically and, with respect to ring substitution and expansion,
follow patterns which relate to the electronic character of the aromatic substituents. With benzene substituted by
electron-releasing methoxy and methyl groups, ring 6 8
substitution (C-H insertion) is the exclusive aromatic
reaction. Benzene however, undergoes only ring expansion
to yield cycloocta[c]pyrrole (55). With the electronically
deactivated substrates, nitrobenzene and benzonitrile, the
major products are cycloocta[c]pyrroles; aromatic
substitution is minor. a, ot, a-Trifluorotoluene gives aromatic substitution and expansion; because the reaction
products could not be separated, the relative partitioning
of 2 into the two reaction patterns is not known.
The ortho and para substitution reactions of 1 with
toluene and anisole are qualitatively similar to those of 5 4 3,5-dichlorobenzene-l, 4-diazooxide (89) and of 5-t-butyl- 25 3-diazopyrazole (21) with these activated benzenes. The 55 chief difference is that 1 is more selective, giving
only p-substitution of anisole, and thus implies that 2 is
a relatively discriminating reactant, possibly for electr
onic and steric reasons. The absence of meta substitution products rules out reactions of 1 and 2 by formal free
radical processes since related arylations of substituted 56 benzenes give mixtures of 2-, 3- and 4-substituted biphenyls.
54 M.J.S. Dewar and K. Narayanaswami, J. Am. Chem. Soc., 86, 2422 (1964).
55 89 gives an orthotpara isomer ratio of 2.68 with anisole; 21 gives an ortho:para isomer ratio of 1.3 and 69
The gross behaviour of 1 with electron rich benzenes thus appears to involve substitution by electrophilic singlet processes. The simplest mechanism for reactions of 1 with activated benzenes involves thermal and photolytic formation of 2s and stepwise aromatic substitution as in
Eq. 67. Such processes will account for ortho and para rather than meta substitution because of the stabilizing effects of the electron-donor substituents as in 90 and
91. For anisole to give exclusive para substitution# 2js would have to be a discriminatory reactant and possibly ortho attach would be seriously sterically retarded.
An alternate mechanistic possibility which has precedent 54 ' 2 5 and is in part a modification of Eq. 67, involves attach of 2js on the substituted benzene to yield spironorcaradienes 92^ by addition to any single double bond of the benzene ring and/or by ring closure of intermediates such as 90 and 91 and their meta isomer.
2.1 with anisole and toluene,respectively. For comparison, 1 forms ortho and para isomers in a 1:1 ratio with toluene T61 and 60) and only the para isomer with anisole (64).
56 D.H. Hey, in "Advances in Free-Radical Chemistry," Vol. II, G.H. Williams, Ed., Academic Press, New Yorh, 1967, pp. 47-86. 70
hv or -M, C6H5.'OS.W; - *6"9 ' * c 6H5 6 5 i 2 s
C H 6 5 C6h5 " CfiH5 C6H5 H 90 (671
V i ,2s 6
'6 5 C6«5 H 91
Heterolytic cleavage of 9J2 at cyclopropane bonds a or b
can thus generate dipolar intermediate 93^ in which the
negative charge is delocalized over the pyrrole ring and
the positive charge is dispersed into the electron donor
cyclohexadienoid system. Proton transfer possibly via
94 completes the sequence (Eq. 68) , giving 95.
X X 2s + |
6H 92 93 (68) X
P H ^ H 6 5 6 5 6 94 95 71 An important aspect of the latter mechanistic sequence is that ring-openings of the spironorcaradiene intermediates play important roles in the overall orientations for aromatic substitution. A substituent X will therefore affect formation and ring cleavage of the spironorcaradiene intermediates. Thus when X is electron releasing in substituted spironorcaradienes, those bonds will be preferentially broken which allow the phenonium ion moieties to be relatively conjugatively stabilized by
X. Such ring cleavages are illustrated for the possible spironorcaradienes derivable from a substituted benzene
(Eq. 69).
^ ortho isomer
X meta isomer
(69) X
Para isomer 72
Failure of electron-donor benzenes to undergo meta substitution is thus understandable.
The other products of reaction of 1 and toluene, 3-benzyl-2,5-diphenylpyrrole (59), 1,2-diphenylethane
(58) and 2,5-diphenylpyrrole (24) deserve mechanistic comment. Formation of 59^ possibly occurs via 2t by abstraction-recombination as for 1 and cumene, although direct insertion by 2js cannot be excluded. Conversion of toluene to 58 presumably involves dimerization of benzyl radicals derived by hydrogen abstraction from toluene by
2t. Further, reduction of 1^ to £4 apparently results from initial hydrogen abstraction by 2t. Analogously, 2 4 from
1 and anisole may arise by hydrogen atom transfer from its methyl group to 2t.
Perhaps the most interesting observations of the present research are the conversions of benzene, benzo- nitrile, nitrobenzene and presumably ot, formation of spironorcaradienes 92, electrocyclic isomerization to spirocycloheptatrienes 99, 1,5 sigmatropic rearrangement to 100 and then hydrogen migration (by concerted 1,5 sigmatropic processes) result in 101. When X = NO2 or CN, these processes each result in a mixture of three isomers presumably because three isomeric initial spironorcaradiene adducts 96, 97, and 98 are formed. C 92 99 (70) > H C 6 6 100 101 74 When X = NC>2 or CN, the phenonium ion moiety formed by heterolytic cleavage of spironorcaradienes 92^ cannot be well stabilized by the electron-withdrawing groups. Instead, the spironorcaradienes 9j2 rearrange by a sequence of electrocyclic reactions as shown in Eq, 70, resulting in cycloocta[c]pyrroles. For X = CH3 or 0CH3, heterolytic cleavage of 9£ is favored as the phenonium ion portion can be stabilized by delocalization, leading to ring sub stitution products. Exclusive formation of cycloocta[c]- pyrrole 5ji in reaction of !L with benzene is not well understood at present. Reaction of diazocyclopentadiene with benzene gives as primary product spironorcaradiene 8, which although 7 unstable, has been isolated and characterized. Prolonged photolysis or thermolysis of 8 in benzene results in the 7 8 more stable bicyclo[6.3.Olundecapentaene 11^ * (see Historical for details). Spironorcaradiene 92 (X = H) analogous to spironorcaradiene 8 could not be isolated in reaction of 1 and benzene. This is probably because of the relative instability of 9£ (X= H) relative to 8 and there fore results in conversion of 92 (X= H) to the more stable and better delocalized cycloocta[c]pyrrole 55. Another 75 possibility, observed with 1,4-disubstituted-5-diazocyclo- pentadienes and benzene is formation of benzocyclohepta- trienes. 57 No such products were found in the reactions of 1 and benzene. As summarized earlier, photosensitization of 1 in benzene and benzonitrile give totally different results than for thermolysis and photolysis. Irradiation of 1 in benzene using thioxanthen-9-one and 4,41-bis(dimethyl- amino)benzophenone (Michler's ketone) as sensitizers thus yields 2,3, 5-triphenylpyrrole (lj6) and in the latter case, 2,5-diphenylpyrrole (24) is also formed. Cycloocta[c]- pyrroles were not found in these experiments. The mechanistic aspects of these photosensitized reactions are not obvious, and adequate interpretation of these results is a formidable task. A possible explanation of the behaviour of 1 on photosensitization is that triplet 1, represented as It, is formed which then decomposes to 2t upon loss of nitrogen (refer to earlier equations for photosensitization). Conversion of diazo compounds by photosensitizers to triplet carbenes is well established, but doubts have been expressed about the intervention of triplet diazo compounds 57 H. Dtlrr and G. Scheppers, Ann. Chem., 73 4, 141 (1970). 76 as intermediates in these processes.^' ^ Benzene may be presumed to undergo addition of lit/ either through carbon or nitrogen of its diazo moiety to give 1,5-diradical 1(12, which after spin inversion closes to pyrazoline 103. Open ing of 103 to 104 by thermal or photochemical (direct or sensitized) processes followed by hydrogen transfer and loss of nitrogen may form the observed product, 2,3,5- triphenylpyrrole (16) (Eq. 71). Loss of nitrogen from 104 prior to hydrogen transfer results in singlet 1, 3-diradical 105, also obtainable by addition of 2it to benzene, followed by intersystem crossing as shown in Eq. 72. Hydrogen migration in 105 directly gives Ij6. At present it is not clear if 105 is involved as an intermediate and if so, why it does not close to spironorcardiene 9J2 (X=H). The mechanisms of photosensitized reactions of 1 in the presence of thioxanthen-9-one and Michler’s ketone are presumably identical. Formation of 2,5-diphenyl- pyrrole (24) upon sensitization with Michler's ketone probably arises from triplet It and/or 2t by hydrogen abstraction from the methyl groups of the photosensitizer which had to be used in high concentration. CO Ref. 37, page 279. 59 M. Jones and W. Ando, J. Am. Chem. Soc., 90, 2200 (1968). A- XX or C6H 5 ” C6H 5 102 1) ISC 1) hv or i 1. ~ — pr "" " ^ 2) ring 2) "hv, sens., H then ISC closure 6 6 5 C6H5 103 104 * N H 5 H transfer -N, > H 6 C 6H 16 78 I'N V -N, r aN T 1?CAi 6 5 °6H5 105 104 ISC J (72) 2t + C H H-transfer ,— V " C6H5 /C6H 5 — ------> JlX • C6H 5/N ^ C6H 5 Cah N ^ C6H 0 5 6 5 H 16 Photosensitized reactions of 1 with benzonitrile and with benzene by thioxanthen-9-one probably proceed through identical mechanisms. Formation of 3-(o-cyanophenyl)-2,5- diphenylpyrrole (70) is thus rationalized by addition of triplet diazopyrrole bt and/or 2t to benzonitrile as in Eq. 73. Attack at the ortho position of benzonitrile by 3* CN CN jN C ^ j Q 1. ;N 1) ISC or i T ^ ’ 2) ring rf No / r ti v C,H 6 5 C6H 5 C6H 5 closure It CN NC N=N, 1) hv or A -N or r ^ c H 2) h\), sens,, C,6 ISC 5 6 ISC (73) 11 CN & C6H 5 C 2t N' NC H-transfer C C 70 80 a triplet reactant (ljt and/or 2t) is consistent with extended delocalization of a diradical intermediate by the cyano group. It is unclear, however, why addition of It and/or 2t to the para position of benzonitrile does not taXe place detectably. Thermal reactions of 1_with aniline and its derivatives were investigated with the expectation that their amino groups would function as electron donors. Since these amines give results quite different from the previous aromatic substrates, their chemistry will now be summarized. Thermolysis of 1 in aniline gives 2,5-diphenyl-3(N- phenylamino)pyrrole (106, 29%) and 2,5-diphenylpyrrole (24, 20%)(Eq. 74). Elemental and mass spectral analyses A -N 2 6 5 6 5 6 5 6 5 1 106 (74) + 6 5 H 6 5 24 81 show 106 to be a 1:1 adduct of 2 and aniline. The IR absorption of 106 has N-H stretching bands at 3430 and 3380 cm-^ and the NMR spectrum displays two broad singlets of equal area at 6 5.06 and 8.13 attributable to aromatic secondary amine N-H and pyrrole N-H, respectively. That C-H substitution of aniline by 2^ does not occur is indicated by the absence of primary amine IR absorptions in the product. In behaviour similar to aniline, N-methylaniline is converted to 3-(N-methyl-N-phenylamino)-2,5-diphenylpyrrole (107/ 27%) and 2,5-diphenylpyrrole (24, 35%) on heating (Eq. 75). That 107 is a 1:1 adduct of 2 and N-methylaniline 2 ™ ch3 „ + ( ° ) -N. C6H5 C6H5 CH_ (75) I 3 ' - V ^ ' C6H 5 + /X C6H 5 h 6 5 C5H5 g C6H5 107 24 82 is established from its elemental analysis and mass spectrum. A metastable peak at m/e - 294- 295 corresponds to the loss of a methyl group from the molecular ion of 107 at m/e - 324. The NMR spectrum of 107 has a 3-proton singlet at 6 3.13 for the N-methyl group and no absorption for aromatic secondary amine N-H, thereby discounting it as a ring substituted derivative. Heating 1 (180-185°) in N,N-dimethylaniline results in 3-(N-methyl-N-phenylaminomethyl)-2,5-diphenylpyrrole (108, 19%), 3-(N-methyl-N-phenylamino)-2,5-diphenylpyrrole (107, 10%), and 2,5-diphenylpyrrole (24, 9%) (Eq. 76) fH 3 1 108 CH 3 (76) + 6 5 107 24 83 along with intractables. Insertion product 108 analyzes for C24H22N2 and its mass sPectrum has, besides the parent peak at m/e — 338, a base peak at m/e = 232 due to the cation radical 109. The absence of reasonably strong peaks at m/fi = 91 and 247 is evidence against 3-(N-benzyl- N-methylamino)-2,5-diphenylpyrrole (110) as the product. The NMR spectrum of 108 has singlet signals at 6 2.85 and CH + 3 6 5 H 6 5 6 5 110 109 4.55, assigned to N-methyl and N-methylene groups, respectively. For comparison, the methyl and methylene absorptions in N-benzyl-N-methylaniline resonate at 6 2.9 4 60 and 4.45, respectively The reactions of 1 with anilines are different from those with other aromatic substrates in that ring substitution and/or expansion do not occur. Formation of 24 in these reactions is presumably via hydrogen abstraction 6t^R.M. Coates and E.F. Johnson, J. Am. Chem. Soc., 93, 4016 (1971). 84 by 2t from amino and/or methyl groups. Attractive paths for conversion of 1 to 106 and 107 are direct insertion of 2s into N-H bonds and/or isomerization of betaine intermediates, as in Eq. 77. It is not yet possible to distinguish between the two mechanisms. H J® C,H 6 5 6 5 6 5 6 5 2s R = H (77) R = CH 3 R R H R - H' i,°6 R = CH3, 107 Reaction of 1 with N,N-dimethylaniline is different from its lower homologs. Adduct 108 is presumably formed by direct insertion of into a C-H bond of the methyl group of N,N-dimethylaniline and/or by abstraction- recombination via 2t. Formal loss of a methylene group 85 leading to 107 is a process more difficult to rationalize since such examples are unknown. A possible path for this conversion is through nitrogen ylid 111 (Eq. 78). Methyl transfer from 111 (by displacement) to N,N-dimethylaniline results in 112 which protonates on isolation to give 107. CH3 ch3 I® I © n - c 6h5 N'-ch, r r CH. _ 3 + c6h 5h(ch3)2 c6h 5 C H ” c 6 5 6 5 6 111 112 C6H5N(CH3)3 (78) 6 5 + / n ( N ' “6“ 5 + H JHL C e H c6 '6H5 l C6H 5 112 107 Another alternative is homolytic cleavage of ill with loss of methyl radical to .113 (Eq. 79) which abstracts a hydrogen from the environment, forming 107. This mechanism is closely related to the Stevens rearrangement, which has been observed in reactions of carbenes and tertiary H-abstraction ^ D D etc. H C6H5 107 amines. 61 ' 62 The main difference in the present mechanism is that radical recombination does not occur as in the Stevens rearrangement. Instead# intermediate 113 undergoes reduction by hydrogen abstraction for reasons as of yet unclear. A detailed mechanistic study of the reactions of various diazo compounds or carbenes with different tertiary amines may throw more light on such transformations. 61v. Franzen and H. Kuntze, Ann. Chem., 627, 15 (1959). ft O W.R. Bamford and T.S. Stevens, J. Chem. Soc., 4675 (1952). B7 In view of the success in altering the behaviour of 1 with alcohols by adding trifluoroacetic acid, investi gation of 1 with aromatic substrates in acidic environments was initiated. All of the systems studied in added acid showed a significant difference in product formation when compared to those in the absence of acid. Photolysis of 1 in benzene in 50% excess of trifluoro acetic acid proceeds cleanly, giving 2,3,5-triphenylpyrrole (16, Eq. 80, 76%) as the only isolable product. Cycloocta[c]pyrrole 55 was not detected. — (80) hv 16 Irradiation of 1 in anisole containing trifluoroacetic acid yields 3-(p-methoxyphenyl)-2,5-diphenylpyrrole (64, 27%) and 3-(o-methoxyphenyl)-2,5-diphenylpyrrole (114, 27%) along with 2,5-diphenylpyrrole (24, 6-7%) (Eq. 81). Thermolysis of 1 in acidic anisole gives 6^4 and 114 (18%) in admixture in 4:1 ratio along with 24 (24%). The NMR OCH- CF.CO H 1 + | U I --- -— ^-=> & hv —N „ 64 CH..O (81) 114 signals of <54 are identical with those of 6j4 obtained from thermolysis of 1 in anisole. The identity of 114 is established by synthesis of an authentic sample (Scheme VII) having identical spectra (IR, NMR and mass spectra) and melting point. The mixture of i64 and 114 from the thermolysis experiment was characterized in part from its NMR spectra and by oxidation with potassium permanganate to a mixture of carboxylic acids which was esterified by diazomethane and analyzed by GC as methyl benzoate and methyl o- and p-methoxybenzoates. Photolysis of 1 and benzonitrile in the presence of trifluoroacetic acid gives 70 as a single product 89 Scheme VII NaOH 1) n-BuLi ^ cjj^o 2) Cul || V - \ C-H-CH(SC-H-)„ ------=> CtHc-CCH0-CH-< O > 6 5 6 5 2 3) 115 in THF 6 5 2 | W c(Sc6h5)2 C,H 5 CuCl 0/CuO ft Q NH.OAc ------C,Ht.-C-CHg-CH-C-C^Hj- --> H„0/acetone | HOAc, A £ 1 .ULnj 6H & 114 116 (19-20%), Eq. 82. Thermolysis of the acidic mixture, however, gives 70 and 3-(e-cyanophenyl)-2,5-diphenylpyrrole CN CF3C02H 1 + (82) hv H -N 6 70 90 (71) in — 1:1 ratio in 50% yield {Eq. 83). IR analysis of the product showed clearly that 70 was one of its ,CN NC CN CF3C°2H 1 + (S J A H -N C6H5 H C6H5 6 70 71 (83) components. The identity of 71^ was confirmed by independent synthesis (Scheme V) and then establishing that the IR spectrum of an authentic mixture of 7£ and 7jL is identical with that from the thermolysis system. Heating (170°) 1 in nitrobenzene/trifluoroacetic acid yields 3-(m-nitrophenyl)-2, 5-diphenylpyrrole (77, 28%) and 3-(o-nitrophenyl)-2,5-diphenylpyrrole (117, 12%) (Eq. 84). NO, cf3co2h NO F\ (84) A H -N. 6 C6H 5 H C6H 5 77 117 91 Meta substitution product T7 is identical with that from thermolysis of 1 in nitrobenzene. Ortho isomer 117 was assigned by elimination after unambiguous synthesis of 3-(p-nitrophenyl)-2, 5-diphenylpyrrole (118) (Scheme VIII). Scheme VIII /— v NaOH / \ H ° 2nAO)-«'o + ch3coc6h 5 c h > ° 2n -\0 >-ch=chc-c6h 5 2 5 2 119 1) n-BuLi 2) Cul2) Cul „ \ C6 H5 CH (SC aH 5 ) _ ------> C.H.C-CH.-CH— < 0> — NO. 2 3) 119 in THF 6 5 2 » c(sc6h 5)2 5 NO 2 CuO/CuCl, fj jj NH .OAc H^O/ace tone HO Ac, A H( 118 NO 120 Dediazonations of aromatic diazonium salts have 6 3 attracted much attention. The phenyl cation has been 6^H. Zollinger, Accts. Chem. Res., 6, 335 (1973). 92 established as an intermediate in decomposition of benzenediazonium tetrafluoroborate.6 ^'66 There is also considerable evidence that p-nitrobenzenediazonium tetra- fluoroborate decomposes homolytically in dimethyl sulfoxide-benzene66 and pyridine changes decomposition of benzenediazonium tetrafluoroborate in 2 ,2, 2-trifluoro- 67 ethanol from heterolytic to homolytic. Unfortunately, no generalizations can be made as to the detailed mechanisms of decomposition of aryldiazonium salts in various environments. ' In the present system, on adding acid, 1 is protonated in part to the 2,5-diphenylpyrrole-3-diazonium ion (3, Eq. 85) . The UV spectrum of 1^ in benzene containing 50% 64C.G. Swain, J.E. Sheats and K.G. Harbison, J . Am. Chem. Soc., 97, 783 (1975). 65 R.G. Bergstrom, R.G.H. Landells, G.H. Wahl and H. Zollinger, J. Am. Chem. Soc., 98, 3301 (1976). 66B. Gloor, B.L. Kaul and H. Zollinger, Helv. Chim. Acta, 55, 1596 (1972). 93 excess trifluoroacetic acid shows that 56% of 1 is converted to 3. Experimentally, photolysis of 1 in acidic benzene yields 2, 3, 5-triphenylpyrrole (1*>); no cycloocta[c]pyrrole 5J5 is formed. Definite interpretation of these results is presently impossible. The data may be rationalized, however, on the basis of (1 ) aromatic substitution of benzene and its derivatives by diazonium ion 3^ or its subsequent cation 48; (2) free radical aromatic substitution by pyrrolyl radical 47; and (3) conversion of !L to 2s, its addition to the aromatic nucleus and subsequent acid-catalyzed collapse of spironorcaradiene 92. All these are illustrated by Eq. 8 6 . The ortho and para substitution products from reaction of 1 with anisole in the presence of added acid can be explained by using any one or combination of the mechanisms in Eq. 8 6 , particularly if radical 4J7 is a highly discriminating intermediate. It is not so easy, however, to interpret the reactions of 1 in acidic benzonitrile and nitrobenzene. Possibly, the reactions proceed through a combination of the various mechanisms detailed above, with some selective intermediates being involved to explain the high degree of specificity observed. gn P. Burri, H. Loewenschuss, H. Zollinger and G.K. Zwolinski, Helv. Chim. Acta* 57, 395 <1974). O o cr> cr\ (Tv tc mW I EC © CTi cn x t6 CHAPTER III. EXPERIMENTAL Melting Points. Melting points were determined using a Thomas Hoover capillary point apparatus and are uncorrected. Elemental Analysis. Elemental analyses were perfor med by Microanalysis, Inc., Wilmington, Delaware, or by Galbraith Laboratories, Inc., Knoxville, Tennessee, or by Scandinavian Microanalytical Laboratory, Herlev, Denmark. Ultraviolet Spectra. Ultraviolet spectra were obtained using a Cary Model 14 recording spectrophotometer. Infrared Spectra. Infrared spectra were determined on Perkin-Elmer Model 137 or 45 7 recording spectrophoto meters. All spectra were calibrated against a polystyrene absorption at 1601 cm-1. Samples were prepared as KBr wafers unless otherwise stated. Nuclear Magnetic Resonance Spectra. Proton magnetic resonance spectra were obtained using Varian Associates nuclear magnetic resonance spectrometers Models A-60A, HA-100, and EM-360L, respectively. Carbon-13 magnetic resonance spectra were run on Bruker Models HX-90 and WP-80 instruments. All spectra were measured in 95 96 chloroform-d solution with tetramethylsilane as internal standard. Spectral assignments are as follows: (1) chemical shift on the 6 scale (2 ) multiplicity: s = singlet, d = doublet, t = triplet, m = multiplet and br = broad; (3) coupling constant in Hertz (Hz); (4) assignment of the signal and (5) number of hydrogens integrated for by the signal. Mass Spectra. Mass spectra were determined by Mr. C.R. Weisenberger on an AEI-MS-9 mass spectrometer. Gas Chromatography. Gas chromatography was performed using Wilkins Aerograph Model HI-FY 600-D with a flame ionization detector. Relative peak areas were obtained by multiplying peak height by peak width at half height. Column Chromatography. Column chromatography was effected on MN Laboratories' "Silica Gel for Column Chromatography," 70-270 mesh. General. All decompositions {both thermal and photolytic) of diazopyrrole were carried out in a nitrogen atmosphere. Unless otherwise stated, all photo- lyses were performed with a Hanovia 45 0 watt medium pressure mercury lamp which was placed in a Pyrex immersion well. The well itself was fitted to a photo chemical reactor containing the solution to be irradiated. 97 All solvents were dried and deoxygenated prior to use in decomposition experiments. 2, 5-Diphenylpyrrole (?4) • 2,5-Diphenylpyrrole (2j4) was prepared in 70- 75% yield starting from trans-1 , 2-dibenzoylethylene. Reduction of an alcoholic solution of trans-1,2-dibenzoyl- ethylene with aqueous sodium dithionite afforded 1,2-di- benzoylethane in 75 - 80% yield; mp (ethanol): 144-145°; 34 (lit. 145.7 - 147 o ). Cyclization of the above 1,4-dike- tone with ammonium acetate in refluxing glacial acetic acid under nitrogen gave 2, 5-diphenylpyrrole(24) in better 3 4 than 95% yield; mp (ethanol): 140-141°; (lit 139-141°); IR: 3450 (pyrrole N-H), 3050(aromatic C-H) , 1605 and 1500 (aromatic), 1480, 1465, 1280, 1270, 1050, 900, 785, 760, 750, and 690 cm-^ (aromatic); NMR: 6 6.53{d, J = 3Hz, pyrrole 3-and 4-H, 2), 7.12-7.67 (m, aromatic H, 10) and 8.38-8.75 (br s, pyrrole N-H, 1); exact mass: calcd. for C16H13N: 219*1047; found: 219.1051. 3-Diazo-2, 5-diphenylpyrrole (_1_ ) . 13 The method of Kreutzberger and Kalter was adopted. 2,5-Diphenylpyrrole (24) was nitrosated with sodium 98 ethoxide and iso-amyl nitrite in absolute ethanol to give 3-nitroso-2,5-diphenylpyrrole in greater than 95% 13 yield; mp: 203-204°; (lit. 204-205°). Reduction of the nitrosopyrrole with Raney Nickel catalyst T-l and hydrogen in 1:1 acetone-2-propanol afforded 3-amino-2,5- diphenylpyrrole in 45-50% yield. The yield of 70% claimed for this reduction by Kreutzberger and Kalter could never be realized. The amine had a melting point 13 of 184-186° (lit. 186-187°). Diazotization of the amine dissolved in 4:1 glacial acetic acid-water (instead of pure glacial acetic acid as reported) with aqueous sodium nitrite followed by in situ neutralization with sodium carbonate solution, all between 0-5°, precipitated the orange-red 3-diazo-2,5-diphenylpyrrole (1 ). It was recrystallized from 5:1 petroleum ether (65-110°)-benzene in the form of shining brownish-red needles; mp 122-12 3° 13 o (decomposes); (lit. 122-123 dec.); IR: 3040 (aromatic C-H), 2100 (diazo), 1600 (aromatic), 1445, 1340, 1310, 1260, 1165, 765, 755 and 690 cm”^ (aromatic); NMR: 66.80 (s, pyrrole 4-H, 1) and 7.05-8.10(m, aromatic H, 10); exact mass: calcd. for C. ,-H., ,N~: 245.0953; found: JLo ± X -i 245.0957. The overall yield of 1 for the three steps starting from 2j4 ranged from 25-30%. Diazopyrrole 1 is a stable and non-explosive compound at room temperature 99 and can be stored for months as a solid in the dark. Exposure of solutions in various solvents ( benzene, chloroform, etc.) to light leads to slow decomposition as indicated by a change in colour. Photolysis in Cyclohexane. A solution of diazopyrrole 1 (0.490 0 , 2.0 mmole) in cyclohexane (145 ml) was irradiated for 2.5 hr. Vacuum concentration of the reaction mixture gave a reddish-brown residue which was chromatographed over silica gel (50 g) and eluted with 2:3 benzene-hexane. The first product off the column was 3-cyclohexyl-2, 5-di phenylpyrrole (2J5, 0.190 g, 31.6%); mp (hexane): 103-104°; IR: 3440 (pyrrole N-H), 3030 (aromatic C-H), 2920 and 2845 (aliphatic C-H), 1600 and 1490 (aromatic), 820, 770, 760 and 690 cm-^ (aromatic); NMR: 6 1.10-2.20(br m, > o ] H, 10) , 2.75 (br m, ^ ' 6.55(d, J = 2.5Hz, H — pyrrole 4-H, 1), 7.0-7.60(m, aromatic H, 10) and 8.0-8.25 (br s, pyrrole N-H, 1); exact mass: calcd. for C22H23N: 301.1830; found: 301.1836. Anal. Calcd. for C22H23^: <~e 87.66; H, 7.69. Pound: C, 87.40; H, 7.82. Further elution gave 2,5-diphenylpyrrole (24, 0.110 g, 25%) , characterized by NMR. 100 Thermolysis in Cyclohexane. Diazopyrrole 1 (0.490 g, 2.0 mmole) in cyclohexane (200 ml) was maintained at 80° for 48 hr. After the excess cyclohexane was removed on a rotary evaporator, the residue was chromatographed on silica gel (75 g) and eluted with 1:1 hexane-benzene. The two isolable products were 3-cyclohexyl-2,5-diphenylpyrrole (25, 0.130 g, 21.6%) and 2,5-diphenylpyrrole (24, 0.070 g, 16%), having identical IR and NMR as authentic samples. Photolysis in Cumene. A solution of 1 (0.490 g, 2.0 mmole) in cumene (175 ml) was photolyzed for 30 min. Excess cumene was removed by vacuum distillation. The residue was chromato graphed on silica gel (100 g) and eluted with petroleum ether (30-60°). The first fraction was 2,3-dimethyl- 2,3-diphenylbutane (27, 0.120 g, 25.2%); mp: 116-118° (lit.68 119-120°); IR: 3020 (aromatic C-H), 2980(aliphatic CH C-H), 1495 (aromatic) , 1440, 1380 and 1365 ( )/ 780 — 1 ^ and 705 cm” (aromatic); NMR: ^ 1.30(s, 12) and 7.10(s, aromatic H, 10); exact mass: calcd. for c ^q H 22: 238.1721; found: 238.1724. The second product was identified as 3-(1-methyl-1-phenylethyl)-2,5-diphenyl pyrrole (28, 0.291 g, 43.2%); mp (hexane): 122-123°; IR: 3445 fc>yrrcle N-H), 2970 (aliphatic C-H), 1600 and 1490 68A. Klages, Ber., 35, 2638 (1902) 101 S/CH3 (aromatic), 1380 and 1360 ( and 700 cm-^ (aromatic) ; NMR: 6 1.62 (s, CH^, 6), 6.70 (d, J = 3Hz, pyrrole 4-H, 1), 6.90-7.60(m, aromatic H, 15) and 8.00- 8.32(br s, pyrrole N-H, 1); exact mass: calcd. for C.,H„-N: 337.1830; found: 337.1836. 25 2 3 Anal. Calcd. for C25H 23N: C, 88.98; H, 6.87; N, 4.15. Found: C, 89.18; H, 7.01; N, 4.22 The last component was 2,5-diphenylpyrrole (24, 0.20 g, 45.6%), characterized by NMR. Thermolysis in Cumene. A cumene solution (200 ml) of 1 (0.490 g, 2.0 mmole) was refluxed for 24 hr. Concentration in vacuo gave a reddish-brown viscous oil, which was chromatographed on silica gel (80 g) and eluted with 1:1 hexane-benzene. The first fraction consisted of 2,3-dimethyl-2,3-diphenyl- butane (27, 0.110 g, 23.1%). The second product was shown to be 3-(1-methyl-l-phenylethyl)-2,5-diphenylpyrrole (28 , 0.295 g, 43.8%). Finally, 2,5-diphenylpyrrole (24) was obtained (0.210 g, 47.5%), identified by NMR. 102 Photolysis in Cyclohexene. A cyclohexene solution (380 ml) of 1 (0.980 g, 4.0 mmole) was photolyzed for 3 hr. Concentration of the photolysate under vacuum gave a viscous red liquid. Careful chromatography on silica gel (135 g) and elution with 3:2 hexane-benzene gave 3-(3-cyclohexenyl)-2,5-di phenylpyrrole ( 29, 0.392 g, 32.8%); m p (hexane) : 80-82°; IR: 3430(pyrrole N-H), 3010(aromatic and olefinic C-H), 2920(aliphatic C-H), 1600 and 1490(aromatic), 820, 770, 760 and 700 cm-^(aromatic); NMR: 6 1.20-2.30(br m, 6), 3.35-3.80(br m 1), 5.75 (br s, olefinic H, 2), 6.50(d, J = 2.5Hz, pyrrole 4-H, 1), 7.0-7.60(m, aromatic H, 10) and 7.90-8.23(br s, pyrrole N-H, 1); exact mass: calcd. for C 22H21N: 299.1673; found: 299.1678. Since this compound could not be purified satisfactorily for analysis, it was reduced to the known 3-cyclohexyl-2,5-diphenylpyrrole 25 (see below) for confirmation of its structure. A second product isolated was identified as 2,5-diphenylpyrrole (24, 0.179 g, 20.5%) by NMR. Reduction of 29 to 2 5 . Pyrrole 29 (0.110 g, 0.368 mmole) in methanol (30 ml) was hydrogenated for 3 hr at 20 psi using 5% Pd/C as 103 catalyst (10 mg). The solution was filtered through Celite and concentrated to a brown solid. Filtration through silica gel (15 g) with 1:1 hexane-benzene yielded 3-cyclohexyl-2/5-diphenylpyrrole (25/ 0.101 g, 91.2%), identical with an authentic sample (IRy NMR, mp and mass spectrum). Thermolysis in Cyclohexene. A mixture of 1^ (0.490 g, 2.0 mmole) and cyclo hexene (200 ml) was maintained at 80° for 1 week. Removal in vacuo of excess cyclohexene left behind a brownish-red viscous liquid which was chromatographed on silica gel (80 g) and eluted with 1:1 hexane-benzene. 3-(3-cyclohexenyl)-2,5-diphenylpyrrole (29, 0.16 g, 26.8%) eluted first, followed by 2,5-diphenylpyrrole (24, 0.105 g, 24%). The structures were established by comparison of IR and NMR spectra with those of authentic samples. Photolysis in 2, 3-Dimethyl-2-butene. A solution of 1^ (0.980 g, 4.0 mmole) in 2, 3-dimethyl- 2-butene (380 ml) was photolyzed for 4 hr. Excess olefin was removed by distillation and the reddish-brown residue chromatographed on silica gel (100 g) and eluted with 1:1 hexane-benzene. The only tractable product was 104 3-(2, 3-dimethyl-2-butenyl)-2,5-diphenylpyrrole (38, 0.465 g, 38.6%); mp(hexane): 96.5-98.0°; IR: 3435(pyrrole N-H), 3040(aromatic C-H), 2900(aliphatic C-H), 1600 and 1490(aromatic), 1275, 910, 820, 780, 770 and 690 cm-1 (aromatic); NMR: 5 1.63 (br s, CH^), 1.73{br s, CH^, together 9), 3.42(br s, -CI^-/ 2), 6.4(d, J = 3Hz, pyrrole 4-H, 1), 7.08-7.67(m, aromatic H, 10) and 8.0-8.42(br s, pyrrole N-H, 1); exact mass: calcd. for C22^23^: 301.1830; found: 301.1834. Anal. Calcd. for C22H 23N: C ' 8*7*66; H, 7.69; N, 4.65. Found: C, 87.33; H, 7.57; N, 4.77. Photolysis in Allylbenzene. Diazopyrrole 1^ (0.490 g, 2.0 mmole) in allylbenzene (175 ml) was photolyzed for 15 min. Excess allylbenzene was distilled off under vacuum and the residue chromato graphed on silica gel (70 g) and eluted with 7:3 hexane- benzene. The first product was identified as 2,5- diphenylpyrrole (24, 0.092 g, 21%) by NMR. The second fraction was a mixture of 2,5-diphenyl-3-(l-phenyl-2- propenyl)pyrrole (4JJ and 2,5-diphenyl-3-(3-phenyl-2- propenyl)pyrrole(£2, 0.22 g, 31.5%); IR (neat): 3440 105 (pyrrole N-H), 3065 and 3040(aromatic and olefinic C-H), 1605 and 15 00(aromatic), 1270, 1075, 1030, 970(C-H out of ^ H plane bending of ), 910 (C-H out of plane bending T J * * ^ of ^-C=:cr' ), 760 and 695 cm x (aromatic); NMR: 6 2.85- H H 3.63(m, allylic H), 4.70-5.23(m, olefinic H), 6.35-6.52 (m, pyrrole 4-H), 6.73-7.62(m, aromatic H), and 8.05-8.35 (br s, pyrrole N-H); mass spectrum: m/e = 335; M+ for C 25H 21N = 335 - Hydrogenation of j41 and 42 . The mixture of 41 and 42 (0.211 g, 0.63 mmole) in ethyl acetate (30 ml) was hydrogenated for 3 hr at 40 psi hydrogen using 5% palladium/ carbon as catalyst (30 mg). The solution was filtered through Celite and concentrated rn vacuo to give a viscous liquid (0.130 g). NMR showed the mixture to be 2,5-diphenyl- 3-(1-phenylpropyl)pyrrole (41a) and 2, 5-diphenyl-3-(3-phenyl- propyl)pyrrole (42a) with signals at 5 0.90 (distorted t, -CH2CH3), 1.85-2.15(br m, -CH2CH3 and -CH2CH2CH2-), 2.62 Ar CH2CH3 (distorted quartet, -CH2-CH2~CH2-) , 3.8 3(m,^^^ 6.42-6.60(m, pyrrole-4H), 6.90-7.62(m,aromatic H) and 8.0-8.33(br s, pyrrole N-H). Integration of the signals at 5 0.90 and 2.62 gave a ratio of 2 1 3 for 41:42. Oxidative Cleavage of 41^ and 42 . To a mixture of 4_l_and _42 (0.168 g, 0.50 mmole) in 4:1 dioxane-water was added 5% osmium tetroxide in ether (5 drops) followed by 106 sodium periodate (0.30 g) in the course of 30 min. The dark brown suspension was stirred for another 30 min and then poured into water. The mixture was extracted with ether (3 x 15 ml), the combined ether extracts washed with water and dried (MgS04). Removal of ether gave a dark brown viscous liquid (0.115 g). Analysis by GC showed the presence of benzaldehyde and the absence of phenylacetaldehyde (20% SE-30 on chrom W 60-80 mesh, NAW, 20' x 1/8", column temperature 205°). 2,5-Diphenylpyrrole (24) was recovered unchanged under identical conditions. Reaction with Allylbenzene. An allylbenzene solution (100 ml) of diazopyrrole 1^ (0.490 g, 2.0 mmole) was maintained at 160° for 1 hr. After distillation to remove excess allylbenzene, the residue was chromatographed on silica gel (70 g) and eluted with 7:3 hexane-benzene. 2,5-Diphenylpyrrole (2j4, 0.135 g, 30.8%) eluted first and was characterized by NMR. Further elution gave a mixture (0.220 g, 32.8%) of 2, 5-diphenyl-3-(1-phenyl- 2-propenyl)pyrrole (41) and 2,5-diphenyl-3-(3-phenyl-2- propenyl)pyrrole (42) ; IR(neat): 3440(pyrrole N-H), 3060 and 3040(aromatic and olefinic C-H), 1605 and 1500(aromatic), ^ yH 1275, 1080, 1035, 970 (C-H out of plane bending of C = C ), S H v 915(C-H out of plane bending of /C-C. 765, 700 and H H 107 690 cm-^ (aromatic); NMR: 6 2.90-3.60(m, allylic H) , 4.68 - 5.25(m, olefinic H) , 6.35-6.50(m, pyrrole 4-H), 6.90-7.55 (m,aromatic H) , and 7.97-8.30(br s, pyrrole N-H); mass spectrum: m/e = 335; M + for C 25H 21N = Hydrogenation of the mixture of £1 and 4_2 as described before gave a viscous oil whose NMR was qualitatively similar to that previously described. Integration of the peaks at 8 0.88 and 2.62 in the NMR of the reduced product mixture gave a ratio of 2:5 for 41: 42 • Oxidative cleavage of the mixture of 41^ and 42 with osmium tetroxide/sodium periodate as before gave a brown liquid which contained only benzaldehyde as revealed by GC analysis (same conditions as reported earlier). Photolysis in MethanoL Diazopyrrole 1 (0.490 g, 2.0 mmole) was dissolved in methanol (175 ml) and irradiated for 4.5 hr. The solution was concentrated under vacuum to a reddish-brown semi-solid and chromatographed on silica gel (50 g), using 7:3 hexane- benzene as eluant. The first product was identified as 2,5-diphenylpyrrole (24, 0.120 g, 27.4%) by NMR. Further elution gave 3-methoxy-2,5-diphenylpyrrole (43, 0.062 g, 12.4%); mp(hexane): 107.5-109°; IR: 3 450(pyrrole N-H), 30 20, 1600 and 1480(aromatic), 1180(C-0-C), 1040, 750 and 690 cm-^ 108 (aromatic); NMR: 6 3.88 (s, OCH3, 3), 6.35{d, J = 3Hz, pyrrole 4-H, 1), 7.10-7.75(m, aromatic H, 10) and 7.95- 8.32(br s, pyrrole N-H, 1); exact mass; calcd. for C^^H^^NO: 249.1153; found: 249.1158. Anal: Calcd. for C ^ H ^ N O : C, 81.90; H, 6.06. Found: C, 81.79; H, 6.18. Photolysis in Acidic Methanol. A solution of 1 (0.490 g, 2.0 mmole) and trifluoro- acetic acid (0.342 g, 3.0 mmole) in methanol (175 ml) was photolyzed for 4.5 hr. After removal of excess methanol under vacuum, the residue was chromatographed on silica gel (50 g) and eluted with 7:3 hexane-benzene. The two products obtained were shown by spectral methods (IR and NMR) to be 2,5-diphenylpyrrole (£4, 0.049 g, 11.2%) and 3-methoxy-2,5- diphenylpyrrole (43, 0.220 g, 44.2%). Reaction with Methanol. A methanolic solution (100 ml) of diazopyrrole 1 (0.245 g, 1.0 mmole) was maintained at 65° for 1 week. The solvent was removed i_n vacuo, leaving behind a brownish-red solid (0.240 g), identified as unchanged 1^ by IR and TLC methods. 109 Photolysis in Isopropanol. Diazopyrrole 1^ (0.490 g, 2.0 mmole) in dry acetone free isopropanol (175 ml) was photolyzed for 45 min. Analysis of an aliquot of the photolysate by GC showed acetone to be present (15% Carbowax 20M on Chrom W, 20* x 1/8", column temperature 65°). The acetone was quantita tively estimated using n-butanal as internal standard (0.0745 g, 64.2%). Removal of excess isopropanol and chromatography of the residue on silica gel (30 g) and elution with 1:1 hexane-benzene gave 2,5-diphenylpyrrole (24, 0.293 g, 66.9%), identified by comparison with an authentic sample. A blank photolysis without 1 did not form any acetone photolytically from isopropanol. Photolysis in Acidic Isopropanol . A solution of !L (0.490 g, 2.0 mmole) and trifluoro- acetic acid (0.342 g, 3.0 mmole) in isopropanol (175 ml) was irradiated for 1 hr. The mixture was concentrated under vacuum and the brownish-red solid chromatographed on silica gel (70 g) and eluted with 1:1 hexane-benzene. The first product off the column was 2,5-diphenylpyrrole (24, 0.137 g, 31.3%), identified by NMR. The second component was shown to be 3-(2-propexy)-2,5-diphenylpyrrole (46, 0.134 g, 24.2%); mp(hexane): 108-109°; IR: 3440(pyrrole 110 N-H), 3020(aromatic C-H), 2980(aliphatic C-H), 1610 and 1500(aromatic), 1390 and 1375(—CH(CH^)2 bending vibrations), 1200, lllO(C-O-C), 770 and 690 cm-^(aromatic); NMR: 6 1.35 (d, J = 6Hz, -CH(CH3)2, 6), 4.37(septet, J « 6Hz, -CH(CH3)2, 1), 6.28(d, J = 2.5Hz, pyrrole-4H, 1), 7.0-7.80(m, aromatic H, 10) and 7.85-8.13(br s, pyrrole N-H, 1); exact mass: calcd. for CigHigNO: 277.146; found: 277.147. Anal. Calcd. for C^gH^gN0: C, 82.28; H, 6,90; N, 5.05. Found: C, 82.17; H, 6.98; N, 5.17. Reaction with Isopropanol. Diazopyrrole 1 (0.245 g, 1.0 mmole) in isopropanol (100 ml) was maintained at 80° for 100 hr. After removal of excess isopropanol under vacuum, the residue was chromatographed on silica gel (30 g) and eluted with 1:1 hexane-benzene to yield 2,5-diphenylpyrrole (24^ 0.130 g, 59.4%), identified by IR and NMR. Reaction with Benzyl Alcohol A solution of 1^ (0.2 45 g, 1.0 mmole) in benzyl alcohol (5 ml) was kept at 150° for 4 hr. Excess benzyl o alcohol was distilled (42-43 /0.08 mm Hg) into saturated ethanolic 2, 4-dinitrophenylhydrazine (15 ml). An orange precipitate formed, which was digested on a steam bath and filtered and dried to give benzaldehyde 2,4-dinitrophenyl- o 69 hydrazone (0.187 g, 65.4%). Mp(ethanol): 235-237 (lit. R.L. Shriner, R.C. Fuson and D.Y. Curtin, The Systematic Identification of Organic Compounds, J. Wiley and Sons, New York, 196 4. Ill 237-238°). The residue from thermolysis of 1 was chromatographed on silica gel (50 g) and eluted with 3:2 benzene-hexane to afford 2,5-diphenylpyrrole (24* 0.154 g, 70.3%) characterized by spectral comparison with an authentic sample. Photolysis in Diethyl Ether. An ethereal solution (175 ml) of diazopyrrole (0.490 g, 2.0 mmole) was cooled to 0° and photolyzed for 2 hr. Excess ether was removed on a rotary evaporator and the residue chromatographed on silica gel (50 g) and eluted with 1:1 hexane-benzene. The only isolable product was identified by NMR as 2,5-diphenylpyrrole (24, 0.036 g, 8 .2%). Photolysis in Acetic Acid. A solution of 1 (0.490 g, 2.0 mmole) in glacial acetic acid (175 ml) was irradiated for 75 min. After a reduced pressure distillation to remove acetic acid, the residue was chromatographed on silica gel (50 g) and eluted with benzene. The first product was identified as 2,5-diphenylpyrrole (24, 0.032 g, 7.3%) by NMR. A second compound was characterized as 3-acetoxy-2,5-diphenylpyrrole (5j., 0.112 g, 20.2%); mp (hexane-benzene) : 122-123°; IR: 3380(pyrrole N-H), 1740( ^=0 of acetate), 1600(aromatic), 1230, 760 and 695 cm*1 (aromatic) ; NMR: 6 2. 22 (s,-OCOCH^ 3, 112 6.45(d, J = 3Hz, pyrrole 4-H, 1), 7.05-7.57(m, aromatic H, 10) and 8.25-8.67(br s, pyrrole N-H, 1); exact mass: calcd. for ciqhi5N02 ; 277.1103; found: 277.1107. Anal. Calcd. for C/ ^.96; 5.45, N, 5.05. Found: C, 77.98; H, 5.34; N, 4.94. Photolysis in Diethvlamine. A solution of 1 (0.490 g, 2.0 mmole) in diethylamine (175 ml) was irradiated for 1 hr and then concentrated. The reddish-brown residue was subjected to chromatography on silica gel (50 g) and elution with 3:1 benzene- petroleum ether (30-60°). There was obtained 0.326 g (74.4%) of 2,5-diphenylpyrrole (24), identified by NMR. Photolysis in Triethylamine. Diazopyrrole 1 (0.490 g, 2.0 mmole) in triethylamine (175 ml) was photolyzed for 10 min and concentrated in vacuo. Chromatography of the residue on silica gel (50 g) and elution with benzene yielded 2,5-diphenylpyrrole (24, 0.263 g, 60%), characterized by NMR. Photolysis in Benzene. Diazopyrrole _1 (0.980 g, 4.0 mmole) in benzene <380 ml) was irradiated for 4 hr. Excess benzene was removed under vacuum and the residue chromatographed on silica gel (100 g) and eluted with 1:1 hexane-benzene. The only 113 isolable product was a yellow solid, identified as 1, 3-diphenyl - 2H-cycloocta [c]pyrrole (5^5, 0.366 g, 31%); mp (hexane-benzene): 196.5-197.5°; IR: 3 430(pyrrole N-H), 3030(aromatic and olefinic C-H), 1640 (olefinic C=C), 1600 and 1470(aromatic), 920, 800, 760 and 690 cm"1 (aromatic); NMR: 6 5.79-6.36(m, olefinic H, 6), 7.12-7.52(m, aromatic H, 10) and 8.07-8.38(br s, pyrrole N-H, 1); Carbon-13 NMR: (in ppm downfield from TMS; TMS = 0): 132.441 (C-l,3 or 10, 10'), 131.033 (C-l,3 or 10,10'), 130.451(C-6,7 ), 130.062(C-5,8), 128.703(C-l2,12', 14,14'), 127.198(C-4,9), 127.101 (C-11,11',15,15'), 126.907(C-13, a a li 13') and 119.381(C-3a,9a); UV 121 (ethanol): X 221 nm (e28,330) 13 H 15 13 14 14 and 330(30,860); exact mass: calcd. for ^22H17N: 295*1361; found: 295.1368. Anal. Calcd. for C ^ H ^ N : C, 89.45; H, 5.80; N, 4.74. Found: C, 89.20; H, 5.75; N, 4.82. Thermolysis in Benzene. A solutionof _1(0.490 g, 2.0 mmole) in benzene (200 ml) was maintained at 80° for 90 hr. Concentration of the mixture gave a reddish-brown residue which was chromato graphed on silica gel (60 g) and eluted with 1:1 hexane- benzene. The first compound eluted was identical by IR 114 and NMR to the product of photolysis of _1__ in benzene, i.e., 1, 3-diphenyl-2 H-cycloocta[c]pyrrole (55^, 0.215 g, 72.9%, based on reacted). Further elution gave _1_ (0.246 g). Thermolysis in Benzene at 175^ A solution of (0.245 g, 1.0 mmole) in benzene (50 ml) was heated with rocking in a glass lined autoclave (American Instrument Co., Model 40-1220) at 175° for 1 hr. After cooling, the contents were poured out and the liner rinsed with benzene and the rinsings added to the product mixture. Concentration under vacuum followed by chromato graphy on silica gel (30 g) and elution with 1:1 hexane- benzene gave as the only isolable product (0.202 g, 68.5%). The IR and NMR of 55_ were identical to that of an authentic sample. Photosensitized Decomposition in Benzene (Thioxanthen-9-one). A benzene solution of 1__ (0.245 g, 1.0 mmole) and thioxanthen-9-one (2.367 g, 11.17 mmole, calculated to absorb at least 95% of the incident light at 380 nm, the for thioxanthen-9-one in benzene) was photolyzed for max ■* 1 hr. Excess benzene was removed under vacuum, leaving behind a brown solid, which was extracted with hot benzene 115 and filtered. This process was repeated thrice to remove the thioxanthen-9-one. Finally, chromatography of the residue from the filtrate over silica gel (50 g) and elution with 1:1 hexane-benzene gave 2,3,5-triphenyl- pyrrole (16, 0.134 g, 45.4%), identical by spectral comparison (IR, NMR) to an authentic sample. Photosensitized Decomposition in Benzene (4,41-Bis(dimethyl- amino)benzophenone). A mixture of (0.061 g, 0.25 mmole) and 4,4'- bis(dimethylamino)benzophenone (Mirhler's Ketone) (1.485 g, 5.5 3 mmole, calculated to absorb at least 95% of the incident light at 380 nm, the high wavelength cut-off for Corning 7-37 filter) in benzene (90 ml) was irradiated through a Corning 7-37 filter (10% transmittance at 335 and 380 nm; greater than 21% at 365 nm) with a Schoeffel Instrument 1000 watt High Pressure Mercury-Xenon lamp for 8 hr. Excess solvent was removed, the residue taXen in chloroform and chromatographed on silica gel (50 g) and eluted with benzene. A mixture (0.022 g) of 2,5-diphenyl pyrrole (2^4) and 2, 3,5-triphenylpyrrole (IjS) was obtained; IR: 3460 and 3420 (pyrrole N-H), 3060 and 3030(aromatic C-H), 1600, 1490, 1465, 1280, 1265, 1160, 1075, 1055, 1030, 116 960, 905, 810, 785, 760 and 695 cm"1 (aromatic)? NMR: 56.55 (d, J = 2.5Hz, pyrrole 4-H), 6.66(d, J = 2Q5Hz, pyrrole 4-H), 7.0-7.65{m, aromatic H) , and 8.10-8.63{br s, pyrrole N-H); mass spectrum: shows peak at m/e = 295(M for 16 = 295) and other fragments characteristic of 16 and 2 4. Integration of the signals at 6 6.55 (_24) and 6.66 (16) gave a 1:1 ratio for 24:16. Photolysis in Acidic Benzene. A benzene solution <175 ml) of 1^ (0.490 g, 2.0 mmole) and -trif luoroacetic acid (0.342 g, 3.0 mmole) was photo- lyzed for 2 hr. Concentration of the photolysate and chromatography of the residue on silica gel (50 g) followed by elution with 1:1 hexane-benzene afforded 2, 3, 5-triphenyl- pyrrole (_16, 0.447 g, 75.8%); mp (hexane) : 140-141 o ; (lit.52 140-141°); IR: 3420(pyrrole N-H), 3030(aromatic C-H), 1600 i and 1490 (aromatic), 960, 830, 760 and 695 cm (aromatic); NMR: 6 6.67(d, J = 2.5Hz, pyrrole 4-H, 1), 7.14-7.65(m, aromatic H, 15) and 8.10-8.47(br s, pyrrole N-H, 1); exact mass: calcd.for C22H17N: 295.1361; found: 295.1368. Photolysis in Toluene. A toluene solution (175 ml) of 1_ (0.490 g, 2.0 mmole) was photolyzed for 1.5 hr and the photolysate 117 concentrated under vacuum. Chromatography of the viscous liquid on silica gel (70 g) and elution with 1:1 hexane- benzene gave as the first product 1,2-diphenylethane (58, 0.014 g, 3.8%). The identity of was established by NMR with signals at 5 2.90 (s, CH2C6H5/ ^ an<^ ^*18 aromatic H, 10). GC analysis showed ^ to be identical with an authentic sample (20% SE-30 on Chrom W, 6 1 x l/8M, column temperature 205°). The second product was an oil (0.236 g) . Crystalli zation from hexane afforded a pale yellow solid identified as 2,5-diphenylpyrrole (^, 0.02 4 g, 5.5%) by NMR. The filtrate was concentrated to an oil (0.210 g) ; IR(neat): 3440(pyrrole N-H), 3060 and 3025(aromatic C-H), 2920 (aliphatic C-H), 1605 and 1490(aromatic), 1455, 1270, 1220, 810, 760 and 695 cm”^ (aromatic); NMR: 8 2.08(s, Ar-CH^), 2.28(s, Ar-CH^), 3.95(s, Ar-CH^), 6.30(d, J = 3Hz, pyrrole 4-H), 6.47(d, J = 3Hz, pyrrole 4-H), 6.58(d, J = 3Hz, pyrrole 4-H), 6.75-7.53(m, aromatic H) and 8.00-8.23(br s, pyrrole N-H); mass spectrum: m/e = 309 (M+ for 309). NMR shows that the oil after removal of 2, 5-diphenyl pyrrole (_^) consists of three products: 3-benzyl-2,5- diphenylpyrrole / 2, 5-diphenyl-3-(p-tolyl)pyrrole (60) and 2,5-diphenyl-3-(o-tolyl)pyrrole (61) obtained in a 118 total yield of 34%. The first two (59 and 60) have been confirmed by independent synthesis (see below). Integration of the signals at 5 2. 08, 2.28, and 3.95 gives the ratio of 6JL:60:5jj as 3-Benzyl-2,5-diphenylpyrrole (59). a. 3-Benzoyl-2,5-diphenylpyrrole. This was prepared 70 o according to the procedure of Sprio, mp 16 4-165 ; lit.70 167°. b. 3-Benzvl-2,5-diphenylpyrrole. A solution of 3-benzoyl-2,5-diphenylpyrrole (1.076 g, 3.33 mmole) in dry THF (tetrahydrofuran ) (10 ml) was added to a solution of 0.96 M diborane in THF (30 ml) under a nitrogen atmosphere. The mixture was stirred at room temperature for 16 hr and excess diborane was destroyed by adding saturated sodium chloride solution (15 ml). The mixture was extracted with ether (3 x 30 ml), the combined ether extracts washed with water and brine and dried (MgSO^). Removal of ether gave 3-benzyl-2,5-diphenylpyrrole (59/ 1.01 g, 98%); mp(hexane): 82-83°; IR: 3440(pyrrole N-H), 70 V. Sprio, Gazz. Chim. Ital. 86, 95 (1956). 119 3060 and 3035(aromatic C-H) , 1605 and 1500(aromatic), 1460, 1455, 1275, 770 and 700 cm-'*'(aromatic); NMR: 6 4.0 (SyArCH^-, 2), 6.37(d, J = 3Hz, pyrrole 4-H, 1), 7.13- 7.60(m, aromatic H, 15) and 8.15-8.40(br s, pyrrole N-H, 1) ; exact mass: calcd. for C23H^gN: 309.1517; found: 309.1523. Anal. Calcd. for C, 89.28; H, 6.19; N, 4.53. Found: C, 89.41; H, 6.05; N, 4.41. 2, 5-Diphenyl-3- (p-tolyl) pyrrole (60^). a. p-Methylbenzylideneacetophenone (62^) . p-Methyl- benzylideneacetophenone (62J was prepared in 86% yield; 71 mp 95-96 o ; lit. 94-96°. o b. 1,4-Diphenyl-2-(p-tolyl)-1,4-butanedione (^) . The ~ ~ 72 method of Mukaiyama and coworkers was adopted as follows. To a dry THF solution (70 ml) of benzaldehyde diphenyl- thioacetal (3.08 g, 10.0 mmole) was added a 2.4M solution of n-butyllithium in hexane (4.17 ml, 10.0 mmole) at -70° under nitrogen and the mixture was stirred for 1 hr. Cuprous iodide (0.955 g, 5.0 mmole) was added all at once and the mixture stirred for an additional hour at -70°. 71 W. Davey and D.J. Tivey, J. Chem. Soc., 1230 (1958). 72T. Mukaiyama, K. Narasaka and M. Furusato, J . Am. Chem. Soc., 94, 8641 (1972). 120 62 (1.11 g, 5.0 mmole) in THF (15 ml) was introduced dropwise at -70° and the mixture stirred at -70° for 2 hr and then quenched toy addition of water (10 ml). After the mixture had warmed to room temperature, the precipitated copper salts were filtered and the THF removed under reduced pressure. The residue was suspended in water and extracted with ether (2 x 40 ml) ; the combined ether extracts were then dried over MgSO^. Removal of ether followed by chromatography on silica gel (60 g) , eluting with 1:1 hexane-benzene, gave 1,4-diphenyl-4,4-bis(phenylthio)-3- (jg-tolyl)-1-butanone (1.33 g, 50%). The crude thioketal (1.325 g, 2.5 mmole) dissolved in 99% aqueous acetone (50 ml) was stirred at room temperature for 1 hr with cupric chloride (0.673 g, 5.0 mmole) and cupric oxide (0.795 g, 10.0 mmole). The heterogenous mixture was filtered and the filtrate concentrated and chromatographed on silica gel (35 g) and eluted with 3:1 benzene-hexane to give 1 ,4-diphenyl-2-(p-tolyl)-1,4-butanedione (63, 0.680 g, 80.1%, 40% from p-methylbenzylideneacetophenone); m p (2-propanol): 88.5-90°; IR: 3060 and 3040(aromatic C-H), 2925(aliphatic C-H), 1680(^=0), 1600(aromatic), 1520, 1455, 1345, 1230, 1010, 1005, 830(aromatic C-H out of plane bending, characteristic of pare-substitution), 795, 750 121 and 695 cm~^(aromatic); NMR: 6 2.20(s, Ar-CH^, 3), 3.17 JAM = 18Hz' JMX = 9Hz' 1 ] ’ 5. 30 (d of d, = 3.5Hz, = 9Hz, 1), 6.90-7.47(m, aromatic c#% H, 10) and 7.83-8.15(m, aromatic 0 H, 4); (NMR spectra of all 1,4 diketones are discussed as per the above projection); exact mass: calcd. for C 23H20°2: 328.1463; found: 328.1470. Anal. Calcd. for C23H20°2: C ' H ' 6.14. Found : C, 84.39; H, 6.24. c. 2,5-Diphenyl-3-(p-tolyl)pyrrole (60). A mixture of diketone 63 (0.328 g, 1.0 mmole) and ammonium acetate (0.462 g, 6.0 mmole) in glacial acetic acid (10 ml), deoxygenated by bubbling nitrogen for 30 min and then maintained at 130° for 5 hr under nitrogen was poured into ice/ammonia solution and the precipitate formed was extracted with ether (3 x 30 ml). The combined ether extracts were washed with water and dried (MgSO^) and concentrated to give 2,5-diphenyl-3-(p-tolyl)pyrrole (60, 0.292 g, 94.5%); mp(hexane): 144-145°; IR: 3420(pyrrole 122 N-H), 3070 and 3030(aromatic C-H), 2920(aliphatic C-H) 1600(aromatic), 1520, 1495, 1270, 1180, 963, 835(aromatic C-H out of plane bending, characteristic of para sub stitution), 800, 770, 765 and 700 cm"'*'(aromatic) ; NMR: 6 2.30(s, Ar-CH^, 3), 6.65(d, J = 3Hz, pyrrole 4-H, 1), 6.85-7.67(m, aromatic H, 14) and 8.20-8.48(br s, pyrrole N-H, 1); exact mass: calcd. for C 23H^gN: 309.1517; found: 309.1526. Anal. Calcd. for C 23HlgN: C, 89.28; H, 6.19? N, 4.53. Pound: C, 89.09; H, 6.35; N, 4.51. Thermolysis in Toluene. Diazopyrrole _1__ (0.490 g, 2.0 mmole) in toluene (100 ml) was maintained at 110° for 14 hr. The solution was concentrated and the residue chromatographed on silica gel (70 g) and eluted with 1:1 hexane-benzene. The first product (0.008 g, 2.2%) was identified as 1,2-diphenyl- ethane ( 58) by GC, using the same conditions as before. Further elution gave an oil (0.320 g) which was dissolved in hot hexane and then cooled. A pale yellow solid deposited which was shown by NMR to be 2, 5-diphenylpyrrole (2£, 0.061 g, 13.9%). 123 Concentration of the filtrate yielded an oil (0.251 g, 40.5%); IR(neat): 3440(pyrrole N-H), 3060 and 3030 (aromatic C-H), 1600 and 1495(aromatic), 1455, 1265, 1220, 760 and 695 cm-1(aromatic); NMR: 6 2.12(s, Ar-CH3), 2.33 (s, Ar-CH^), 4.0(s, Ar-CH2-), 6.35(d, J = 3Hz, pyrrole 4-H), 6.52 (d, J= 3Hz, pyrrole 4-H), 6.63(d, J=2.5Hz, pyrrole 4-H), 6.85-7.63(m, aromatic H) and 8.05-8.30(br s, pyrrole N-H); mass spectrum: m/e = 309 (M+ for C23H ]_9N = 309)- Tlle oil is a mixture of 61, 60, and 59^ as shown by NMR and their relative ratio by integration of the signals at 6 2.12, 2.33 and 4.0 is 1:1:1. Reaction with Anisole Diazopyrrole (0.490 g, 2.0 mmole) in anisole (100 ml) was maintained at 160° for 45 min. Removal of excess anisole by vacuum distillation left behind a brown, gummy residue which was chromatographed on silica gel (50 g) and eluted with 1:1 hexane-benzene. The first fraction was identified as 2,5-diphenylpyrrole (_2f, 0.094g, 15.9%) by NMR. Continued elution gave 3-(p-methoxyphenyl)- 2, 5-diphenylpyrrole (<54, 0.325 g, 50%); mp (isopropanol) : 116-118°; IR: 3400(pyrrole N-H), 3030(aromatic C-H), 1600 and 1485(aromatic), 1220(C-0-C), 1165, 945, 830 124 (aromatic C-H out of plane bending, characteristic of para-substitution), 760 and 695 cm-'*' (aromatic) ; NMR: 6 3.73 (s, -0CHv 3), 6.62 (d, J = 3Hz, pyrrole 4-H, 1), 6.78 J H (distorted doublet, J = 8Hz, ^O^-^OCH^, part of AA'BB' pattern, 2}, 6.93-7.63(m, aromatic H, 12) and 8.17-8.50 (br s, pyrrole N-H, 1); exact mass: calcd. for 325.1466? found: 325.1473. 3-(p-Methoxyphenyl)-2, 5-diphenylpyrrole (64), a. p-Methoxybenzylideneacetophenone (65)• Chaleone 65 was prepared from p-anisaldehyde and acetophenone in 77% yield; mp: 74-75° (lit.73 76°). b. 2-(p-Methoxyphenyl)-1,4-diphenyl-l,4-butanedione (66). Diketone 66 was obtained according to the procedure of 74 Stetter and Schreckenberg. To a suspension of sodium cyanide (0.049 g, 1.0 mmole) in dry dimethylformamide (DMF, 5 ml) at 35° under nitrogen was added a EM.F solution (7 ml) of benzoin (1.06 g, 5.0 mmole) in 5 min and stirred for an additional 5 min. ^5 (1.785 g, 7.5 mmole) in DMF (10 ml) was introduced in 10 min and stirred at 35° for 73 J.B. Conant and E.P. Kohler, J. Am. Chem. Soc., 39, 1699 (1917). 74H. Stetter and M. Schreckenberg, Chem. Ber., 107, 2453 (1974). 125 20 hr. The reaction mixture was poured into water and extracted with chloroform (3 x 30 ml). The combined chloroform extracts were washed thoroughly with water and dried (MgSO^). Removal of chloroform gave 2-(p-methoxy- phenyl)-1,4-diphenyl-l/4-butanedione (66, 1.40 g, 54.2%); m p (2-propanol): 138-139°; IR: 3050(aromatic C-H), 1670 ()=0), 1600(aromatic), 1500, 1440, 1225, 1025, 990, 830 (aromatic C-H out of plane bending, characteristic of para substitution), 760 and 700 cm-^(aromatic); NMR: 63.25 (d of d, = 17Hz, = 4Hz, Ha , 1), 3.72 (s, ArOCH3, 3), 4.18 (d of d, = 17Hz, = 9Hz, 1), 5.30(d of d, = 4Hz, = 9 Hz, Hy, 1), 6.82 (distorted d, part of AA*BB' pattern, J = 9Hz, aromatic H, 8) and 7.83-8.16(m, aromatic H, 4); exact mass: calcd. for C 23H 20°3: 34^.1412; found: 344.1420. Anal. Calcd. for C 23H20°3: C ' 80.21; H, 5.85. Found: C, 79.97; H, 5.98 3- (p-Methoxyphenyl) -2, 5-diphenylpyrrole ( 64), A solution of diketone ^6 (0.688 g, 2.0 mmole) and ammonium acetate (0.924 g, 12.0 mmole) in glacial acetic acid (10 ml) under nitrogen was maintained at 130° for 3 hr. Work up as before yielded 3-(p-methoxyphenyl)-2,5- diphenylpyrrcle (64, 0.623 g, 95%); mp(2-propanol): 116- 117°. IR and NMR were identical to that of ( 64) obtained 126 from thermolysis of 1__ in anisole. Exact mass: calcd. for Cj-jH^gNO: 325.1466; found: 325.1473. Anal. Calcd. for C23^gNO: c, 84.89; H, 5.88; N, 4.30. Found: C, 84.76; H, 6.02; N, 4.27. Photolysis in Anisole . An anisole solution (175 ml) of (0.490 g/ 2.0 mmole) was photolyzed for 2 hr and the photolysate concentrated to a brown residue. Chromatography of the residue on silica gel (50 g) and elution with 1:1 hexane- benzene afforded two products. They were 2, 5-diphenyl pyrrole (24, 0.038 g, 8.7%) and 3-(p-methoxyphenyl)-2, 5- diphenylpyrrole ( 64, 0.277 g, 42.6%). Identification was by comparison of IR and NMR spectra with those of authentic samples. Reaction with Acidic Anisole . A solution of (0.490 g, 2.0 mmole) and trifluoro- acetic acid (0.342 g, 3.0 mmole) in anisole (100 ml) was maintained at 160° for 1 hr. Excess anisole was removed by vacuum distillation and the residue was chromatographed on silica gel (50 g) and eluted with 1:1 hexane-benzene. The first compound to elute from the column was 127 2,5-diphenylpyrrole (2 4, 0.106 g, 24.2%). Further elution gave a mixture of 3-(p-methoxyphenyl)-2, 5-diphenylpyrrole (64) and 3-(p-methoxyphenyl)-2,5-diphenylpyrrole (114) (0.118 g, 18.1%) as an oil; IR (neat); 3420(pyrrole N-H), 3040, 3010(aromatic C-H), 1605 and 1490(aromatic), 1250, 1220(C-0-C), 1170, 1030, 955, 830(aromatic C-H out of plane bend characteristic of para substitution), 760 and 695 cm”^(aromatic); NMR: 6 3.67(s, OCH^ of ortho isomer), 3.75(s, OCH^ of para isomer), (see spectra of authentic samples for these two assignments), 6.56-7.62(m, pyrrole 4-H and aromatic H) and 8.15-8.52(br s, pyrrole N-H); exact mass: calcd. for C23Hi9NO: 325.1466; found: 325.1473. Integration of the peaks at 6 3.67 and 3.75 showed the ratio of the ortho isomer to the para isomer to be 1:4. Confirmation that the product is a mixture of the ortho and para isomers was obtained by degradation with potassium permanganate to a mixture containing the corresponding anisic acids, esterification by diazomethane and analysis of the esters by GC using authentic samples for comparison. Oxidation of the Mixture of JS4 and 314 with Potassium Permanganate. The mixture of 64 and 114 (0.130 g, 0.40 mmole) in acetone (2 ml) was added to potassium permanganate 128 (0.474 g, 3.0 mmole) in water (10 ml) and heated to 130° for 3 hr. The reaction mixture was filtered hot and the clear basic filtrate was acidified to pH 2 with conc. HC1. A milky white suspension formed, which was extracted with ether (2 x 10 ml); the combined ether extracts were washed with water, brine and dried (MgSO^) . Removal of ether gave a mixture of acids as a pale yellow solid (0.039 g); NMR: 6 3.87(s, OCH3), 4.03(s, 0CH3), 6.82-7.67 (m, aromatic H) , 7.95-8.23(m, aromatic H) and 9.67(br s, COOH). Esterification of the Acid Mixture with Piazomethane. A solution of the mixture of acids (0.030 g) in ether (10 ml) was treated with ethereal diazomethane (generated from 1 g of N-nitroso-N-methylurea as per Ore. Syn. Coll. Vol. II, page 165) at 0° and allowed to stand for 30 min. Acetic acid was added in drops to destroy excess diazo methane and the ether solution was washed with saturated sodium bicarbonate (5 ml), water and dried (MgSO^). Removal of ether gave an oil (0.029 g). Analysis by GC (20% SE-30 on Chrom W 60-80 mesh, NAW, 20' x 1/8", column temperature 245°) showed the presence of methyl benzoate, methyl o-methoxybenzoate and methyl p-methoxybenzoate, as confirmed by co-injection with authentic samples. 129 Photolysis in Acidic Anisole* A solution of (0.490 g, 2.0 mmole) and trifluoro- acetic acid (0.342 g, 3.0 mmole) in anisole (175 ml) was irradiated for 2 hr and the photolysate concentrated under vacuum. Chromatography of the residue on silica gel (50 g) and elution with 1:1 hexane-benzene gave three isolable products. The first compound was shown by NMR to be 2/5-diphenylpyrrole (2 4, 0.029 g, 6.6%). The second fraction consisted of 3-(p-methoxyphenyl)-2, 5-diphenyl pyrrole (64, 0.177 g, 27.2%), having superimposable IR and NMR with that of an authentic sample. The third component was 3-(p-methoxyphenyl)-2, 5-diphenylpyrrole (114, 0.179 g, 27.5%); mp(hexane-benzene): 135-136°; IR: 3370(pyrrole N-H), 3035(aromatic C-H), 2920(aliphatic C-H), 1600 and 1490(aromatic), 1460, 1250, 1180, 1125, 1030, 760 and 695 cm- 1 (aromatic); NMR: 6 3.50(s, -OCH^/ 3), 6.65(d, J = 3Hz, pyrrole 4-H, 1), 6.70-7.63(m, aromatic H, 14) and 8.20- 8.45(br s, pyrrole N-H, 1); exact mass: calcd. for C2^HigNO: 325.1466; found: 325.1473. 3- (o-Methoxyphenyl) - 2, 5-diphenylpyrrole (114), a. o-Methoxybenzylideneacetophenone (H5) . Condensation of o-methoxybenzaldehyde and acetophenone in the presence 130 of alcoholic sodium hydroxide afforded 115 in 52.5% yield; 75 mp: 60-61°; lit. 58-59°. b. 2-(o-Methoxyphenyl)-1/4-diphenyl-1/4-butanedione (116) . The previously employed sequence of reactions to prepare diketone ^3 was followed. Thus, starting with o-methoxybenzylideneacetophenone (115/ 1.19 g, 5.0 mmole), 2-(o-methoxyphenyl)-1,4-diphenyl-1, 4-butanedione (116) was obtained in 60% yield (1.03 g); mp(2-propanol): 119-120°; IR: 3060(aromatic C-H), 2920(aliphatic C-H), 1670 ( ^=0), 1600, 1580(aromatic), 1500, 1450, 1385, 1240, 1000, 965, 760 and 690 cm-^(aromatic); NMR: 6 3.15(d of d, = AM 18Hz, = 3.5Hz, H , 1), 3.85(s, -ArOCH3, 3), 4.30(d of d, = 18Hz, = 9Hz, Hj^, 1), 5.73 (d of d, = 3.5Hz, = 9Hz, H^, 1), 6.80-7.60 (m, aromatic H, 10) and 7.97- 8.25 (m, aromatic H, 4); exact mass: calcd. for C23H20°3: 344.1412; found: 344.1420. Anal. Calcd. for C2 jH2q 0 3: C, 80.21; H, 5.85. Found: C, 80.15; H, 5.80. c. 3- (o-Methoxyphenyl) -2, 5-diphenylpyrrole (n^4) . Condensation of diketone 116 (0.80 g, 2.32 mmole) and ammonium acetate (1.074 g, 13.9 mmole) in glacial acetic 75 H. Stobbe and F.J. Wilson, J. Chem. Soc., 97, 1722 (1910). 131 acid (25 ml) under nitrogen at 140° for 6 "hr gave 3-(o-methoxyphenyl)-2, 5-diphenylpyrrole (114, 0.756 g, 95%); mp(hexane-benzene): 136-137°; its IR and NMR were superimposable on that of 114 (the third product of photolysis of 1^ in acidic anisole); exact mass: calcd. for C23H19NO: 325.1466; found: 325.1473. Anal. Calcd. for C ^ H ^ N O : 84.89; H, 5.88; N, 4.30. Found: C/ 85.16; H, 6.07; N, 4.16. Thermolysis in Benzonitrile . • A mixture of 1 (0.490 g, 2.0 mmole) and benzonitrile (100 ml) was heated to 180° for 1 hr. Concentration of the resulting solution under vacuum gave a red gum which was chromatographed on silica gel (100 g) and eluted with benzene. A bright yellow solid was obtained which was shown by 13 C NMR to be a mixture of 4-, 5-and 6-cyano-l,3- diphenyl— 2H-cycloocta [c ] pyrroles (_67, ^68, and 69, 0.30 g, 46.9%) (see Results and Discusaon); mp(hexane-benzene): 176-179°; IR: 3300(pyrrole N-H), 3050 and 3020(aromatic and olefinic C-H), 2220 (-CN), 1640(olefinic C=C), 1605 and 1485(aromatic), 900, 805, 765 and 695 cm“^(aromatic); NMR: 6 5.50-6.88(m, olefinic H, 5), 7.23-7.60(m, aromatic H, 10) and 8.50-8.90(br s, pyrrole N-H, 1); exact mass: calcd. for C23Hi &N2: 320.1313; found: 320.1318. Anal. Calcd. for C23H16N2: C/ ®^.22; H, 5.03; N, 8.75. Found: C, 86.50; H, 5.30; N, 8.26. Photolysis in Benzonitrile . Diazopyrrole (0.490 g, 2.0 mmole)' in benzonitrile (175 ml) was photolyzed for 6 hr. The photolysate was concentrated and the residue chromatographed on silica gel (75 g) and eluted with benzene. A yellow solid, identified as a mixture of 67^ 68i, and 69^ and having identical IR and NMR to that of the previous mixture from thermolysis of 1^ in benzonitrile, was obtained (0.227 g, 35.5%); mp (hexane-benzene): 175-178°; exact mass: calcd. for 2 6 lo 2 320.1313; found : 320.1321. Photosensitized Decomposition in Benzonitrile. A solution of 1_ (0.245 g, 1.0 mmole) and thioxanthen- 9-one (2.367 g, 11.17 mmole, calculated to absorb > 95% of the incident light at 380 nm) in benzonitrile (175 ml) was photolyzed for 4 hr. Excess benzonitrile was removed in vacuo and the residue extracted with hot benzene and filtered to remove thioxanthen-9-one (thrice). The filtrate was concentrated and chromatographed on silica gel (60 g) and eluted with 1:1 hexane-benzene. The only 133 tractable product was a pale yellow solid, identified as 3-(o-cyanophenyl)-2,5-diphenylpyrrole (70' 0.062 g, 19.4%); mp(hexane-benzene): 197.5-198.5° IR: 3360(pyrrole N-H), 3060(aromatic C-H), 2230(-CN), 1600 and 1490(aromatic), 1300, 1275, 1160, 1080, 960, 920, 910, 815, 765, and 700 cm-^(aromatic); NMR: 5 6.70(d, J = 2.5Hz, pyrrole 4-H, 1) , 7.03-7.70(m, aromatic H, 14) and 8.58-8.83(br s, pyrrole N-H, 1); exact mass: calcd. for C23Hi6N 2 : 320-1313; found: 320.1321. Anal. Calcd. for ^23^16^2: ®^.22; 5.03; N, 8.74. Found: C, 86.05; H, 5.18; N, 8.59. Photolysis in Acidic Benzonitrile. A mixture of 1^_ (0.490 g, 2.0 mmole) and trifluoro- acetic acid (0.342 g, 3.0 mmole) in benzonitrile (130 ml) was irradiated for 6 hr. The photolysate was concentrated to a dark residue and chromatographed on silica gel (70 g). Elution with benzene gave only one isolable product, 3-(o-cyanophenyl)-2,5-diphenylpyrrole (70, 0.110 g, 19.6%); mp(hexane-benzene): 197-198°; exact mass: calcd. for C 23H16N 2: 320*1313* found: 320.1321. The IR and NMR of 70 were identical to that of the product of photo sensitized decomposition of 1 in benzonitrile. Thermolysis in Acidic Benzonitrile. A solution of (0.490 g, 2.0 mmole) and trifluoro- acetic acid (0.342 g, 3.0 mmole) in benzonitrile (100 ml) was maintained at 180° for 1.5 hr. Excess benzonitrile was removed by vacuum distillation and the red residue was chromatographed on silica gel (50 g) and eluted with benzene. A mixture of 3-(o-cyanophenyl)-2, 5-diphenyl pyrrole (70) and 3-(p-cyanophenyl)-2,5-diphenylpyrrole (^71) (0.320 g, 50%) was obtained; (see Results and Discussion for details); mp(hexane-benzene): softens at 163-166°, melts at 184-188°; IR: 3360, 3310(pyrrole N-H), 3040(aromatic C-H), 2225 (-CN), 1600 and 1490(aromatic) , 1295, 1270, 1075, 960, 915, 845, 815, 765, and 695 cm"1 (aromatic); NMR: 6 6.57(d, J = 2.5Hz, pyrrole 4-H), 6.70 (d, J = 2.5Hz, pyrrole 4-H) (together integrating for 1H), 6.85-7.60(m, aromatic H, 14) and 8.58-8.90(br s, pyrrole N-H, 1); exact mass: calcd. for C^_HiJ=N_: 320.1313; found “ 23 16 2 320.1321 . 3- (p-Cyanophenyl) -2, 5-diphenylpyrrole (7JH. a. p-Cyanobenzylideneacetophenone (73^) . p-Cyanobenzyl deneacetophenone (7 3) was prepared according to the 76 procedure of Maclean and Widdows in 86.8% yield from 76 I.S. Maclean and S.T. Widdows, J. Chem. Soc., 105, 2169(1914). 135 p-cyanobenzaldehyde and acetophenone; mp 15 3-154°; lit.76 156-157°. b. 2- (p-Cyanophenyl) -1, 4-diphenyl-l, 4- butanedione ( 7 4). Diketone 74was prepared by the same method as diketone 63. Thus, 3-(p-cyanophenyl)-4,4-bis(phenylthio)-1,4-diphenyl- 1-butanone (2.0 g, 74%) was obtained starting from ^3 (1.165 g, 5.0 mmole). Hydrolysis of the thioketal (1.084 g, 2.0 mmole) with cupric chloride/cupric oxide in 99% aqueous acetone as before afforded 2-(p-cyanophenyl)-1,4- diphenyl-1, 4-butanedione ( 74, 0.572 g, 84.4% from the thioketal); mp(ethanol): 161.5-162°; IR: 3060(aromatic C-H), 2990(aliphatic C-H), 2240(-CN), 1670()=0), 1600, 1490(aromatic), 845(aromatic C-H out of plane bending, characteristic of para substitution), 760 and 700 cm-'*' (aromatic); NMR: 5 3.32(d of d, = 17.5Hz, = 5Hz, AM AX Ha, 1), 4.18 (d of d, = 17.5Hz, = 9Hz, 1), 5.42 (d of d, = 5Hz, = 9Hz, H ^ 1), 7.15-7.67(m, aromatic H,10); and 7.80-8.15(m, aromatic H, 4); exact mass: calcd, for ^ 2 3 ^ 1 7 ^ 2 : 339,1259; found: 339.1265. Anal. Calcd. for C23H17N02: C, 81.40; H, 5.05; N, 4.13. Found: C, 81.46; H, 5.17; N, 4.21. 136 3-(p-Cyanophenyl)-2,5-diphenylpyrrole < J71). Refluxing a mixture of diketone ^74 (0.339 g, 1.0 mmole) and ammonium acetate (0.462 g, 6.0 mmole) in glacial acetic acid (4 ml) at 130° for 3 hr under nitrogen afforded 3-(p-cyanophenyl)-2, 5-diphenylpyrrole (71, 0.251 g, 78.4%); m p (2-propanol): 230.5-231.5°; IR: 3320(pyrrole N-H), 3050(aromatic C-H), 2235(-CN), 1605 and 1480(aromatic), 1180, 960, 845(aromatic C-H out of plane bending, characteristic of para substitution), 765 and 695 cm~^ (aromatic); NMR: 6 6.70(d, J = 2Hz, pyrrole 4-H, 1), 7.09-7.85(m, aromatic H, 14) and 8.45-8.60(br s, pyrrole N-H, 1); exact mass: calcd. for C23H16N2: 320.1313; found: 320.1321. Anal. Calcd. for C23H16N 2: C' 86-22; H' 5*03'* N ' 8.74. Found: C, 85.95; H, 5.16; N, 8.78. 3-(m-Cyanophenyl)-2, 5-diphenylpyrrole (72). a. m-Cyanobenzylideneacetophenone (75). 10% Sodium - - - - hydroxide solution (10 ml) was added dropwi.se to a methanolie solution (125 ml) of m-cyanobenza1dehyde (3.275 g, 25.0 mmole) and acetophenone (3.0 g, 25.0 mmole) at -10°. The mixture was stirred overnight during which 137 time a pale yellow precipitate separated. The mixture was diluted with an equal volume of water, cooled and filtered to yield m-cyanobenzylideneacetophenone (.ZJ?' 4.528 g, 77.1%); m p (2-propanol): 114-115°; IR: 3065 (aromatic and olefinic C-H), 2240(-ON), 1670 (or, unsaturated ^=0), 1605(aromatic), 1435, 1375, 1222, 1027, 995, 775, 690 and 670 cm*1 (aromatic); NMR: 6 7.23-7.90 (m, aromatic and olefinic H, 8) and 7.95-8.17(m, aromatic H, 3); exact mass: calcd. for 233.0840; found: 233.0845. Anal. Calcd. for C ^ H ^ N O : C, 82.38; H, 4.75; N, 6.00. Found; C, 82.50; H, 4.69; N, 5.94. b. 2-(m-Cyanophenyl)-1,4-diphenyl-l,4-butanedione (76). Conjugate addition of lithium [or , or-bis (phenylthio) - benzyljcopper to 7-5 (1.165 g, 5.0 mmole) and hydrolysis of the intermediate ketodithioketal as described in the preparation of 6^3 afforded 2-(m-cyanophenyl)-1,4-diphenyl- I, 4-butanedione (76, 0.681 g, 40.2% from 7J5) ; mp (2-propanol) 143-144°; IR; 3065(aromatic C-H), 2920(aliphatic C-H), 2240(-CN), 1670 ( )=0), 1600(aromatic), 1465, 1260, 1220, 1005, 780, 745 and 690 cm- 1 (aromatic); NMR; 6 3.30 (d of d, = 18Hz, JH = 4Hz, Ha , 1), 4.17 (d of d, = 18Hz, 138 JMX = 9Hz' 1)# 5'40(d °f d ' JAX = 4Hz' JMX = 9Hz' 1), 7.0-7.77(m, aromatic H, 10) and 7.85-8.20 (m, aromatic H, 4); exact mass: calcd. for 339.1259; found: 339.1268. Anal. Calcd. for : c, 81.40; H, 5.05; N, 4.13. Found: C, 81.43; H, 5.42; N, 4.11. c. 3-(m-Cyanophenyl)-2,5-diphenylpyrrole {12). Cyclization of diketone 76^ (0.510 g, 1.5 mmole) with ammonium acetate (0.693 g, 9.0 mmole) in glacial acetic acid (15 ml) at 130° for 4 hr under nitrogen yielded 3-(m-cyanophenyl)-2/5-diphenylpyrrole (72^ 0.424 g, 88.3%); m p (2-propanol): 189-190°; IR: 3320(pyrrole N-H), 3060 (aromatic C-H), 2245(-CN), 1605 and 1490(aromatic), 1275, 900, 820, 810, 795, 770, 760 and 705 cm- 1 (aromatic); NMR: 6 6.67(d, J = 2.5Hz, pyrrole 4-H, 1), 7.23-7.75(m, aromatic H, 14) and 8.35-8.60(br s, pyrrole N-H, 1); exact mass: calcd. for C„-.H1iE.N-: 320.1313; found: 320.1321. Zo l o Z Anal. Calcd. for C23H16N2 : C, 86.22; H, 5.03; N, 8.74. Found: C, 86.09; H, 5.10; N, 8.62. 139 Thermolysis in Nitrobenzene. A nitrobenzene solution (50 ml) of (0.245 g, 1.0 o mmole) was maintained at 170 for 25 min. Excess nitro benzene was removed by vacuum distillation and the residue chromatographed over silica gel (50 g) and eluted with 65:35 benzene-petroleum ether (30-60°). Three products were separated. The first compound was identified as 3-(m-nitrophenyl)-2, 5-diphenylpyrrole ( 77, 0.033 g, 9.7%); mp(isopropanol): 135.5-137°; IR: 3390(pyrrole N-H), 3040 (aromatic C-H), 1595(aromatic), 15 30 and 13 40(-NO^)/ 1110, 810, 765, 750 and 700 cm- 1 (aromatic); NMR: & 6.60(d, J = 2.5Hz, pyrrole 4-H, 1), 7.0-7.63(m, aromatic H, 12), 7.75-8.20 (m, [, 2) and 8. 42-8.67 (br s, pyrrole N-H, 1)? exact mass:calcd. for Co„H.-N-022 16 2 2 340.1216; found: 340.1220 Anal. Calcd. for C 2 2H16N 2°2 C, 77.63; H, 4.74; N, 8.23 Found: C, 77.50; H, 4.82; N, 8.26 The second fraction was a mixture of 4- and 6-nitro-l,3- diphenyl—.2H-cycloocta [ c ] pyrroles (J78) and (79) (0.046 g, 13.5%) (see Results and Discussion for this assignment); mp(benzene): softens at 154-156°, decomposes at 220-223° 140 IR: 3420(pyrrole N-H), 3030(aromatic C-H), 1610(aromatic), 1520 and 1335(_N02), 855, 770, 755 and 695 cm-^(aromatic); NMR: 6 5.75-6.63(m, olefinic H, 3), 7.03-7.67(m, aromatic and olefinic H, 12) and 8.25-8.58(br s, pyrrole N-H, 1); exact mass: calcd. for (-22^16N 2°2: 340.1216; found: 340.1220. Anal. Calcd. for *^22^16^2°2: 77.63; H, 4.74; N, 8.23. Found: C, 77.77; H, 4.92; N, 8.21. The final product was characterized as 5-nitro-l,3- diphenyl— 2H -cycloocta[ c 1 pyrrole (80* 0.060 g, 17.6%) (se6 Results and Discussion); mp(hexane-benzene): 210- 211°; IR: 3350(pyrrole N-H), 3040(aromatic and olefinic C-H), 1630(olefinic C=C), 1600 and 1480(aromatic), 1300 (nitro), 1015, 910, 770 and 700 cm-^(aromatic); NMR: 6 6.0-6.22(m, olefinic H, 2), 7.03-7.67(m, aromatic and olefinic H, 12), 7.85(s, olefinic H, 1) and 8.57-8.93 (br s, pyrrole N-H, 1); exact mass: calcd. for C 22H16N 2°2: 340.1216; found: 340.1220. Anal. Calcd. for *^22^16® 2° 2 ' <"'/ ^7.63; H, 4.74; N, 8.23. Found: C, 78.05; H, 4.93; N, 8.28. 141 Oxidative Degradation of 1 1 . To a solution of potassium permanganate (0.47 4 g, 3.0 mmole) in water (10 ml) was added T 7 (0.204 g, 0.6 mmole). The mixture was maintained at 130° for 3 hr and then filtered hot. The clear filtrate upon acidification with concentrated hydrochloric acid to pH 2 gave a white suspension. The suspension was extracted with ether (2 x 20 ml) and then the combined ether extracts were washed with water and brine and dried (MgSO^). Removal of ether gave a white solid (0.059 g); NMR: <5 7.21-7.94{m, aromatic n o 2 H), 8.03-8. 48 (m, aromatic H), 8.94(s, aromatic H, [q Y'~ ^ IJ and 10.75(br s, -COOH). The signal at 6 8.94 agrees 2 with that reported for m-nitrobenzoic acid at 6 8.96 NCb - H ) * The mixture probably contains some m-nitro- ^ c o 2h benzoic acid. Esterification of the Above Acid Mixture with Piazomethane. The mixture (0.050 g) in ether (10 ml) was treated with ethereal diazomethane (generated from 1 g of N-nitroso- -N-methylurea as per Org. Syn. Coll. Volume II, p. 165) at 0° for 30 min. Acetic acid was added in drops to destroy excess diazomethane and the ether solution was washed with saturated sodium bicarbonate, water and brine and dried (MgSO^). Removal of ether gave an oil {0.048 g). Analysis by GC revealed the presence of methyl benzoate and methyl m-nitrobenzoate and confirmed by co-injection with authentic samples (20% SE-30 on 60/80 mesh Chrom W, 20' x 1/8", column temperature at 245°). Thermolysis in Acidic Nitrobenzene. Diazopyrrole ^1_ (0,245 g, 1.0 mmole) and trifluoro- acetic acid (0.171 g, 1.5 mmole) in nitrobenzene (50 ml) were heated to 170° for 25 min. Concentration under vacuum resulted in a red residue which was chromatographed on silica gel (50 g) and eluted with 65:35 benzene- petroleum ether (30-60°). The initial product eluting from the column was identified as 3-(m-nitrophenyl)-2, 5- diphenylpyrrole (77^ 0.096 g, 28.2%) by spectral compari son (IR and NMR) with an authentic sample. The second product was a red solid, tentatively characterized as 3-(o-nitrophenyl)-2,5-diphenylpyrrole (317, 0.041 g, 12.0%); mp: 66-70°; IR: 3400 (pyrrole N-H), 3040(aromatic C—H), 1600(aromatic), 1520 and 1350(-NO^), 855, 755 and 695 cm**^" (aromatic) ; NMR: 5 6.50 (d, J = 3Hz, pyrrole 4-H, 1), 7.07-7.80(m, aromatic H, 14) and 8.33-8.67(br s, pyrrole N-H, 1); mass spectrum: m/e = 340; M+ for 143 3- (p-Nitrophenyl) -2, 5-diphenylpyrrole (3JS), a. p-Nitrobenzylideneacetophenone (119S . Condensation of p-nitrobenzaldehyde and acetophenone in the presence of alcoholic sodium hydroxide afforded p-nitrobenzylidene- 77 acetophenone in 86% yield; mp 162-164°; lit. 164°. b. 2-(p-Nitrophenyl)-1, 4-diphenyl-l, 4-butanedione (120) . Using the same procedure as detailed for diketone 63, p-nitrobenzylideneacetophenone (119, 1.265 g, 5.0 mmole) was converted to 3-(p-nitrophenyl)-4,4-bis(phenylthio)- 1,4-diphenyl-1-butanone (0.750 g, 26.8%). Hydrolysis of the dithioketal (0.280 g, 0.5 mmole) as before gave 2-(p-nitrophenyl)-1,4-diphenyl-l,4-butanedione (120, 0.160 g, 88.8%); mp(ethanol): 146.5-147.5°; IR: 3060(aromatic C-H), 1670( ^=0), 1600(aromatic), 1510 and 1310(-NC^J , 1240, 1205, 1000, 850(aromatic C-H out of plane bending, characteristic of para-substi tut ion) , 755 and 695 cm”*' (aromatic); NMR: 6 3.35 (d of d, J... = 18Hz, = 4.5Hz, AM AX Ha, 1), 4.22 (d of d, = 18Hz, = 9Hz, H^, 1), 5.48 (d of d, = 4.5Hz, = 9Hz, H ^ 1), 7.23-7.70(m, aromatic H, 8) and 7.85-8.27(m, aromatic H, 6); exact mass: calcd. for C22H17N°4 : 359.1157; found: 359.1164. __ W. Davey and J.R. Gwilt, J. Chem. Soc., 1008 (1957). 144 Anal. Calcd. for C 22H17NC>4: C, 73.53; H, 4.77; N, 3.90. Found: C, 73.59; H, 4.92; N, 3.96. c. 3- (p -Nitrophenyl) -2, 5-diphenylpyrrole (118) . Ring closure of diketone 120 (0.255 g, 0.71 mmole) with ammonium acetate (0.445 g, 4.26 mmole) in glacial acetic acid (15 ml) at 140° for 6 hr under nitrogen gave 3-(p-nitrophenyl)- 2, 5-diphenylpyrrole (113, 0.227 g, 94%); m p (2-propanol): 217.5-219°; IR: 3400(pyrrole N-H ), 3050(aromatic C-H), 1600 (aromatic) , 1505, 1330 (-NC>2) , 1110, 850 (aromatic C-H out of plane bending, characteristic of para substitution), 760 and 695 cm”'*'(aromatic) ; NMR: 6 6.73(d, J = 2.5Hz, pyrrole 4-H, 1), 7.15-8.17(m, aromatic H, 14) and 11.35- 11.50(br s, pyrrole N-H, 1); exact mass: calcd. for C^-H^N-O-: 340.1211; found: 340.1217. ZZ ±t> Z Z Anal. Calcd. for C 22H16N 2°2: 77.63; H, 4.74; N, 8.23. Found: C, 77.62; H, 4.82; N, 8.10. Photolysis in O',or tot— Trif luorotoluene . A solution of diazopyrrole 1^_ (0.490 g, 2.0 mmole) in a,a,»-trifluorotoluene (175 ml) was photolyzed for 1.5 hr. A red polymeric solid deposited on the walls of the vessel and was not investigated. Concentration of the mixture under vacuum gave a sticky red solid which was chromato graphed on silica gel (50 g) and eluted with 55:45 145 petroleum ether (30-60°}-benzene. A yellow viscous oil (0.320 g) was the only isolable product; IR(neat): 3440 (pyrrole N-H), 3065 and 3040(aromatic C-H), 1600 and 1495 (aromatic), 1335, 1300, 1170, 1125, 850, 810, 755 and 690 cm~^(aromatic); NMR: 6 5. 83-6.67(m, olefinic H and pyrrole 4-H), 7.10-7.65(m, aromatic H), and 8.15-8.30 (br s, pyrrole N-H); mass spectrum; m/e = 363 (M+ for C_-,H, ,NF- = 363). On exchange of the product with 2 J ID 6 deuterium oxide/potassium carbonate, one of the doublets of the multiplet (at 6 6.64) collapsed to a singlet, indicat ing that some aromatic substitution had occurred. The product is probably a mixture of 2, 5-diphenyl-3(o, m and p- trifluoromethylphenyl)pyrroles (8,3, 84, and 85) and 1, 3-diphenyl-4-, 5-and 6-trifluoromethyl—. 2H-cycloocta[c]- pyrroles (86/ 87, and 88) (see Results and Discussion for details). Thermolysis in Aniline. A solution of _1^ (0.980 g, 4.0 mmole) in aniline (150 ml) was maintained at 180° for 2 hr. Concentration under vacuum and chromatography of the dark brown residue on silica gel (80 g) and elution with 1:1 hexane-benzene afforded two isolable products. The first compound was 146 identified as 2, 5-diphenylpyrrole (^4/ 0.180 g, 20.5%) by NMR. The second product was shown to be 2,5-diphenyl- 3-(N-phenylamino)pyrrole (106 0.361 g, 29.1%); mp(hexane): 141-142°; IR: 3425 and 3380(pyrrole and amino N-H), 3045 and 3020(aromatic C-H), 1605 and 1495(aromatic), 1440, 1275, 760 and 695 cm-^(aromatic); NMR: 6 5.06(br s, amino N-H, 1), 6.47(d, J = 2.5Hz, pyrrole 4-H, 1), 6.70- “ H ~ 6.80(distorted d, J = 7Hz, -Hh J q ) , 2), 7.0-7.63(m, H ^ aromatic H, 13) and 7.95-8.30(br s, pyrrole N-H, 1); exact mass: calcd. for ^22^18^2: 310.1470; found: 310.1476. Anal. Calcd. for C22H18N2: C ' 85.13; H, 5.85; N, 9.02. Pound: C, 85.15; H, 5.87; N, 9.01. Thermolysis in N-Methylaniline. A mixture of diazopyrrole 1^_ (0.490 g, 2.0 mmole) and N-methylaniline (100 ml) was heated to 180-185° for 1 hr. The solution was concentrated and the residue chromato graphed on silica gel (80 g) and eluted with 7:3 hexane- benzene. Two tractable products could be isolated. The first was identified as 2,5-diphenylpyrrole (24, 0.155 g, 35.4%) by NMR. The second compound was characterized as 3- (N-methyl-N-phenylamino)-2, 5-diphenylpyrrole 0.07/ 0.174 g, 26.9%); mp (hexane): 121-122°; IR: 3420(pyrrole N-H), 147 3040(aromatic C-H), 2880{aliphatic C-H), 1600 and 1500 (aromatic), 1440, 1350, 1300, 1275, 995, 770, 755 and 700 cm"^(aromatic); NMR: 6 3.13(s, -N-CH^, 3), 6.40(d, H N J = 3Hz, pyrrole 4-H, 1), 6, 67-6. 90 (m, 7.63 (m, aromatic H, 13) and 8.13-8.40(br s, pyrrole N-H, 1); exact mass: calcd. for C238 20^2! 324.1626; found: 324.1634. Anal» Calcd. for C23H 20N 2 : C/ 6-21; N, 8.63. Found: C, 85.22; H, 6.27; N, 8.56. Thermolysis in N, N-Dimethylaniline. A solution of (0.980 g, 4.0 mmole) in N, N-dimethyl- aniline (150 ml) was maintained at 180-185° for 2 hr. Excess amine was removed by vacuum distillation and the residue was chromatographed over silica gel (100 g) and eluted with 1:1 bexane-benzene. Three products were isolated. The first was identified as 2,5-diphenylpyrrole (24, 0.076 g, 8.7%). The second component was 3-(N-methyl- N-phenylamino)-2,5-diphenylpyrrole (107, 0.132 g, 10.4%), identical in mp, IR and NMR to the product obtained from reaction of 1 with N-methylaniline. The final compound was 3-(N-methyl-N-phenylaminomethyl)-2,5-diphenylpyrrole 148 (10JB, 0. 266 g, 19.4%); mp(hexane): 122-123°; IR: 3435 (pyrrole N-H), 3050(aromatic C-H), 2900(aliphatic C-H), 1600, 1515, 1510, 1380, 1350, 1265, 1225, 820, 770, 750 and 695 cm"^(aromatic); NMR: 5 2.85(s, -N-CH^ 3), 4.55 (s, -N-CH^-, 2), 6.43(d, J = 3Hz, pyrrole 4-H, 1), 6.62- 6.90(m,H^H, 2), 7.03-7.50 (m, aromatic H, 13) and 8.12- 8.35(br s, pyrrole N-H, 1); exact mass: calcd. for C^.H^N-: 338.1783; found: 338.1788. 24 22 2 Anal. Calcd. for C24H22N2: 85.17; H, 6.55; N, 8.28. Found: C, 85.28; H, 6.49; N, 8.31. REFERENCES 1. W. von E. Doering and C.H. DePuy, J. Am. Cbem. Soc.f 75, 5955 (1953). 2 . R. Gleiter and R. Hoffmann, J. Am. Chem. Soc., 90, 5457 (1968). 3. E. Wasserman, L. Barash, A.M. Trozzolo, R.W. 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