sulfonic-carboxylic anhydrides even if heated for 24 h at 100 OC[’], non-activated arenes such as benzene are acylated smoothly by the mixed anhydrides (3) , without addition of Friedel-Crafts catalysts (Table 2). The trifluoromethane- sulfonic acid can be recovered almost quantitatively as its barium salt.

with strong Br~nsted acids, though in poor yields[31. How- ever, the trifluoromethanegulfonic-carboxylic anhydrides obtainable from acyl chlorides and CF,SO,H do smoothly acylate aromatic compounds without addition of a cata- lyst14]; in the course of the reaction, the sulfonic acid is set free again. Therefore, CF,SO,H-catalyzed acylation of

Table 2. Acylation of aromatic compounds by anhydrides (3).

Reactants Conditions Product [b] (3), R Arene T W ) t ( h )

Yield ( %)

C6HS

C6H3

C6H5

C6H5

C6H5 p-NO,-C6H4 p-N02-C6H4 CH3 (CH312CH

Benzene Benzene Benzene Anisole Chlorobenzene Benzene Anisole Anisole Anisole

-20 5 +20 5 +60 5 +20 0.5 f 6 0 5 +so 1 +40 0.1 -70 2 [a] +40 3.5 [a]

Benzophenone Benzophenone Benzophenone 4-Methox ybenzophenone 4-Chlorobenzophenone 4-Nitrobenzophenone 4-Methoxy-4‘-nitrobenzophenone Acetophenone Isopropyl phenyl ketone

5 52 90 77 67 53 84 66 69

[a] The anhydride (3) was prepared in CH,Cl, and allowed to react directly in this solutlon with the aromatic compound. [b] The acylation products obtained were compared with authentic material.

Received: December 16,1971 [Z 579a IE] German version: Angew. Chem. 84,294 (1971)

aromatic compounds with acyl chlorides appeared a possibility.

[l] Electrophilic Substitution ofAromatic Compounds, Part 1.-This work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. [2] a) R. L. Honsen, J. Org. Chem. 30,4322 (1965); b) A. Streitwieserjr., C. L. Wiikins, and E . Kie lmnn, J. Amer. Chem. SOC. 90, 1598 (1968); c) Tah Mun Su, U? F . Sliwinski, and P. u. R. Schleyer, ibid. 91,5386 (1969). [3] J. March; Advanced Organic Chemistry. Reactions, Mechanisms, and Structure. McGraw-Hill, New York 1968, p. 413ff. [4] a] A. Baroni, Atti Accad. Naz. Lincei, Mem., Cl. Sci. Fis., Mat. Natur. 17, 1081 (1933); b) C. G. Ouerberger and E. Sarlo, J. Amer. Chem. SOC. 85,2446 (1963); c) G. A. Oiah and S. J . Kuhn, J. Org. Chem. 27,2667 (1962); d) H. Bohme and K.-H. Meyer-Duiheuer, Liebigs Ann. Chem. 688, 78 (1965); e) E. Sario and T Lanigan, Org. Prepar. and Proced. 1, 157 (1969). [5] M. If. Karger and Y. Mazur, J. Org. Chem. 36,528,532,540 (1971).

If a catalytic amount (- 1 %) of CF,SO,H is added to a mixture of acyl chloride ( I ) and aromatic compound (2), hydrogen chloride is evolved more or less violently, depend- ing on the reactivity of the reactants, and aromatic ketones (3) (Table 1) are formed. In many cases carboxylic anhydrides may be made to react under similar conditions, but the yields are then slightly lower.

Table 1. Formation of aromatic ketones by catalytic Friedel-Crafts acylation.

Yield o:p ( %)

C 6 H S Benzene 80 8.5 Benzophenone 14 C6H5 Chlorobenzene 132 5 2- and 4-Chlorobenzophenone 13 1 :3 C6H5 Toluene 110 48 2- and 4-Methylbenzophenone 85 1 :2

p-N 0,-C6H, Benzene 80 4 4-Nitrobenzophenone 82 (CH3)3C Anisole 154 12 t-Butyl p-methoxyphenyl ketone 54 (CHJ2CH Anisole 154 0.2 Isopropyl p-methoxyphenyl ketone 46

C6H5 p-Xylene 138 6 2,5-Dimethylbenzophenone 82

Catalytic Friedel-Crafts Acylation of Aromatic

By Franz Effenberger and Gerhard EppleI’]

For the synthesis of aryl ketones from aromatic compounds and acid chlorides or anhydrides at least one equivalent of Friedel-Crafts catalyst is required[’]. Highly activated arenes such as mesitylene or anisole may be acylated also

[*] Prof. Dr. F. Effenberger and Dip1.-Chem. G. Epple Institut fur Organische Chemie der Universitat 7000 Stuttgart, Azenbergstrasse 14-18 (Germany)

Trifluoromethanesulfonic-carboxylic anhydride^'^] formed as intermediates could be assumed to constitute the active acylating agent; on the other hand, the acylating potential of the acyl chlorides may also be increased sufficiently by protonation of the C=O group. We have therefore studied the catalytic efficiency of other strong Bronsted and Lewis acids. As shown in Table 2, catalytic acylation of arenes is possible in principle also with other acids; the yields, though, are of little preparative interest. Perchloric acid which has about the same acid strength as trifluorometh- anesulfonic acid”] is a considerably less effective catalyst. This finding supports our assumption that intermediate

300 Angew. Chem. internat. Edil. / Vol. I 1 (1972) J No. 4

formation of mixed anhydrides is decisive for the catalytic influence of trifluoromethanesulfonic acid ; a final decision, however, is not yet possible.

Table 2. Catalytic action of Brsnsted and Lewis acids in the acylation of p-xylene by benzoyl chloride.

Catalyst Amount Conditions Yield ( %) T("C) f (h) ( %)

CF,SO,H FSO,H p-CH,-C6H4-S0,H HzSO, HCIO, CF,COOH HPOF, AICI, SnCl,

1 1 1 1 1 2.6 3.1 2 2 __

138 138 138 138 138 138 138 138 138

6 82 6 20 6 31 6 28 6 14

10 21 10 4 1s 26 15 30

2,5-Dimethylbenzophenone :

Benzoyl chloride (42 g) and p-xylene (95.5 g) are mixed and treated with trifluoromethanesulfonic acid (0.42 g), then heated for 6 h under reflux. After cooling, the reaction mixture is washed several times with water, dried over sodium sulfate and fractionated, yielding 82% (51.6 g) of 2,5-dimethylbenzophenone, b. p. 173-175 "C/12 torr. For recovery of the catalyst, the aqueous phases are neutralized with barium carbonate, and evaporated.

Received : December 16, 1971 [Z 579 b IE] German version : Angew. Chem. 84,295 (1972)

[l] Electrophilic Substitution of Aromatic Compounds, Part 2.- Part 1 : [4].-This work was supported by the Deuische Forschungsge- meinschaft and the Fonds der Chemischen Industrie. [2] See G. A. Olah: Friedel-Crafts and Related Reactions. Interscience, New York 1964, Vol. 3, pp. 8& [3] a) F. Unger, Liebigs Ann. Chem. 504, 267 (1933); b) R . E . Foster, US-Pat. 2496786 (1950), €.I. du Pont de Nemours; Chem. Abstr. 44, 4930b (1950): c) G. N . Doroleenko. Zh. Obshch. K h m 31,994 (1961). r4] F. Effeenberger and G. Epple, Angew. Chem. 84,294 (1972); Angew. Chem. internat. Edit. 11, 299 (1972). [5] Th. Cramsted,Tidsskr. Kjemi, Bergvesen Met. 19,62 (1959); Chem. Ahstr. 54, 12739 (1960).

C-C-Bond Formation in the a-Position to Nitrogen in Secondary Amines. Lithiodimethylnitrosamine[**]

By Dieter Seebach and Dieter Enders"'

In 1970 Keefer and Fodor published data showing that base-catalyzed H/D-exchange occurs in the a-position of nitrosamines[21. The synthetic availability of corresponding anions (2) would offer a novel type of route to amine molecules. Thus, nitrosation of a secondary amine ( I ) , metalation to give a derivative of / 2 j , reaction with an electrophile to form (3), and denitrosati~n[~I represent a way of carrying out the valuable electrophilic substitution (1 : + ( 4 ) which is not feasible by known

[*I Prof. Dr. D. Seebach and D. tnders Institut fur Organische Chemie der Universitat 63 Giessen, Ludwigstrasse 21, (Germany)

[**! Most nitrosamines are organolropic carcinogens [l] All mani- pulations must be carried out with due care. However, cancer research scientists are interested in testing new !ypes of nitrosamines which might become available through organometallic derivatives. We thank Prof. Dr. H. Druckrey, Freiburg, and Dr. R . Preussmann, Heidel- berg, for valuable discussions.-Financial support by the Fonds der Chemischen Industrie is appreciated.

R / \ N-H

\A

We were able to verify the sequence (1)+{2j+(3) using dimethylnitrosamine (DMNA) and a number of electrophiles ; there are numerous examples in the li- teraturer3I for the facile last step (3) + ( 4 ) in the above cycle.

/,N - O H + n-C3H7-C\

H

+ OH I

C,H,CHO C6H5-CH-CH2, Li - CH2, N-NO =D N - N O

H3C/ H3C/ (6) (5b)

In our first metalation experiments with DMNA it turned out that nucleophilic attack at the nitroso group and metalation at the methyl group of DMNA compete when organolithium compounds are employed : sequential addition of n-butyllithium and benzophenone to a solution of DMNA in THF at -80°C furnished a mixture con- taining both the adduct (Sa) and butyraldehyde oxime. Similarly, the highest yield of carbinol (5b) obtained

R - CH2\

H3C' N - N O (5)

Table. Yields (not optimized), melting- and boiling points of nitrosamines (5 ) from DMNA [a] [the electrophiles were added 10 min after the solutions of DMNA and lithium diisopropylamide had been combined (total volume 40 ml THF/hexane 8 :2 per 10 mmol); the mixtures were kept at - 80°C for 5-lOh].

Electrophile is), R [a1 Yield M.p. ('C) or -

[%] b.p. ("C'torr) [b]

Methll lodide ii-But!l iodide Benz\l bromide ii-Butyraldehyde Benzddehvde Ckclohexdnone

2-Cqclohexen- 1-e

Benzophenone

CH, n-C,H9 C,H,-CH, ~I-C,H,-CHOH C,H,-CHOH 1 -h) droxycyclo- hexvl

lne I -h \dru \ \ c)clohexeii~ I (C,H,J,CC)H

75 80130 [c] 75 10OjlO [d] 95 1OO/Oi [el 80 12011 95 73

90 63 (140/02)

7sp- j 1400s 70 1135

[a] All new compoun$ gave correct elemental analyses and showed IR- [5a] and NMR spectra [S b] typical of nitrosamines. [b] Bath temperature, short path distillation. [c] B p. 70"C/35 torr 161. [d] B p. 96-98"C/13 torr [6]. [el B.p. 116"C/2 torr [6]. [fj The spectra indicate the presence of little if any Michael adduct.

Angew. Chem. inrernat. Edii. 1 Vol. I 1 (1972) /I No. 4 301