1'01.
s4! S o . 4, April 1969
DIFLUORAMINE 917
When addition was complete, the mixture was stirred for an additional 15 min, and then the layers were separated. The organic layer was dried over anhydrous sodium sulfate, methylene chloride was removed by rotary evaporation, and vacuum distillation of the residue gave the desired product in 55% yield: bp 34" (16 mm), n% 1.4609 Clit.19 bp 30" (16 mm), n% 1.46391. Reaction of N,N-Dichloroisopropylamine" with Aluminum Chloride.-The preparation of N,N-dichloroisopropylamine was the same as that described for N,N-dichloro-&butylamine. I n a '250-ml, three-necked flask equipped with stirrer, thermometer, dropping funnel, and condenser were placed 6.7 g (0.05 mol) of aluminuni chloride and 26 ml of methylene chloride. The mixture was cooled between -25 and -30", and 56 ml of a methylene chloride solution of N,N-dichloroisopropylamine (0.05 mol) was added quickly. An aliquot of the reaction mixture (homogeneous) was taken and the nmr spectrum recorded at -22". The spectrum showed a heptet at 3.95 ppm for the methyl groups, 1/6 ratio for CH/CHa, and was the same as that of N,N-dichloroisopropylamine. When the solution in the nmr tube was allowed to warm to -lo", a new doublet appeared at 2.95 ppm which increased with time, whereas the doublet due to the methyl protons of X,N-dichloroisopropylamine decreased and then disappeared. The reaction mixture was subjected to the same conditions as for the sample. Aliquots were taken periodically until the iimr spectrum showed the disappearance of the peaks attributed to N,N-dichloroisopropylamine. (40) H. E. Baumgarten and F. A. Bower, ibid., 76, 4561 (1954).
After addition of water, the layers were separated. Glpc analysis of the organic layer revealed a single product which was collected and identified as acetone from the infrared and nmr spectra. By means of an internal standard, the yield was calculated to be 42%. Visible and Ultraviolet Spectra of the Reaction Mixture from 2-Cbloropropane and Trichloramine-Aluminum Chloride.-The general amination procedure for sec-alkyl halides was followed. After addition was complete, the temperature of the reaction mixture was kept at -5 to -10". There was no solid remaining in the reaction mixture. A 2-ml aliquot was taken and placed in a separatory funnel containing 10 ml of water and 8 ml of methylene chloride. The spectrum of the organic layer showed a maximum at 320 mC. The temperature was allowed to increase to 20". At 10-min intervals, aliquots were taken, quenched, and the spectrum recorded. The maximum shifted to 312 mp with a decrease in intensity until after 230 min there was no discernible maxinwm.
Registry No.-Trichloramine, 10025-85-1 ; aluminum chloride, 7446-70-0; t-butyl chloride, 507-20-0; t-butyl bromide, 507-19-7. Acknowledgment.-We are grateful to the National Institutes of Health, Public Health Service, for partial support of this work.
Reactions of Difluoramine with *-Hydroxy Ketones1 and a,@-Diketonesin the Presence of Sulfuric Acid K. F. MUELLER AND M. J. CZIESLA Chemistry Research, Naval Ordnance Station Indian Head, Indian Head, Maryland 90640 Received August 86, 1968 a-Hydroxy ketones in fuming sulfuric acid undergo reaction with difluoramine to form substituted 4-difluoramino-l,3-dioxa-%thiolane 2,a-dioxides. Under similar conditions, a,p-diketones give substituted 4 , s bis(difluorarnino)-l,3-dioxa-%thiolane 2,2-dioxides. Difluoramine was generated in situ by the interaction of N,N-difluorourea with sulfuric acid.
The preparation of a large number of organic compounds containing difluoramino groups has been reported in the past several years. Most of these compounds have been synthesized either by direct fluorination2-' or by reactions involving tetrafluorohydra~ine.~-'~ The use of diflu~ramine'~-'~ for intro(1) This work was supported by the Independent Research Program of the Director of Naval Laboratories. (2) V. Grakauskas. Abstract of the 140th National Meeting of the American Chemical Society. Chicapo, 111.. Sept 1961,p 23M. (3) R. E. Banks, R. N. Hazeldine, and J. P. Lalu, Chem. Ind. (London), 1803 (1964). (4) G. W. Frazer and J. M. Streeve, Chem. Commun., 532 (1966). (5) M. A. Englin, S. P. Makarov. S. 8. Dubov, and A. Ya. Yakubovich, Zh. Obehch. Khim, 86, 1415 (1965);Chem. Ab&., 68, 14344 (1965). (6) R. J. Koshar, D. R. Husted, and R. A. Meiklejohn, J . Org. Chem., 81, 4232 (1966). (7) R . E. Banks, R. N. Hazeldine, and J. P. Lalu. J . Chem. Soc., C, 1514 (1966). (8)J. P. Freeman, Advances in Chemistry Series, No. 36,American Chemical Society, Washington, D.C., 1962,p 128. (9) A. L. Logothetis, U. S. Patent 3,196,167(1965);U. S. Patent 3,215,709 (1965). (IO) A. L. Logothetis, J . O w . Chem., 81. 3618 (1965). (11)A. L. Logothetis, ibid., 81, 3689 (1966). (12) K. L. Knunyants, B. L. Diatkin, and R. A. Bekker, Im. Akad. Nauk SSSR, Ser. Khim., 1124 (1966);Chem Abdr., 65, 10490 (1966). (13)C. B. Colburn, Chum. Brit., 2.336 (1966). (14) M. J. Cziesla, K. F. IIueller, and 0. Jones, Tetrahedron Leu., 813 (1906).
ducing difluoramino groups into organic molecules?O-n has been reported in the literature in only a few caaes. It is believed that the latter reactions involve the formation of an intermediate carbonium ion, which subsequently alkylates the difluoramine. A new reaction has been found that is in agreement with this theory. This reaction involves the condensation of a-hydroxy ketones or a,@-diketoneswith difluoramine and fuming sulfuric acid. The main products of this reaction are substituted 4-difluoramino-1,3-dioxsi2thiolane 2,2-dioxides (1) and substituted 4,5-bis(difluoramino)-1,3-dioxa-2-thiolane 2,2-dioxides (2), respectively. The compounds are prepared in a one-step procedure. A solution of N,N-difluorourea2 and the ketone in methylene chloride is treated with concentrated sulfuric (15) R. C. Petry and J. P. Freeman, J . Org. Chem., 89, 4034 (1967). (16)A. Kennedy and C. B. Colburn, J . Amur. Chum. Soe., 81,2906 (1959). (17) E. A. Lawton and J. Q. Weber, ibid., 81,4744 (1959). (18) J. P. Freeman, A. Kennedy, and C. B. Colburn, ibid., 82, 5304 (1960). (19) A. V. Fokin and Yu. M. Kosyrev, Usp. Khim., 85, 1897 (1966). (20) R. P. Rhodes, U. 5. Patent 3,345,389(1967). (21) J. P. Freeman, W. H. Graham, and C. 0. Parker, J . A m . C h . Soc., 90, 121 (1968). (22) J. K. Ruff, Chcm. Rev., 67, 665 (1967).
The Journal of Organic Chemistry
MUELLERAND CZIESLA
918
1
NF, NFt
RC-CR'
1 11
HP%
-I- 2"F,
0 0
I
1
I
I
R C 4 R '
os.oo ;
+
2Hz0
Experimental Section
2
acid containing 307, sulfur trioxide. First, the acid decomposes the difluorourea into difluoramine, carbon dioxide, and ammonium hydrogen s ~ l f a t e . ~Then, ?~~ NHZCNFz
/I
+ 2HB04 +HNF2 + COz + NH~HSOI+ SO8
0
the difluoramine reacts with the ketone and additional sulfuric acid. Although intermediate compounds could not be isolated from these reactions, a mechanism is given in Scheme I which reasonably explains the products isolated. SCHEME I
1
3
RC-cR' (b)
I II 0 0
2HNF2
4
elemental analysis, infrared spectroscopy, and nuclear magnetic resonance spectroscopy. The infrared spectra showed strong N-F absorption between 1040 and 820 cm-'. Two bands were observed for the cyclic sulfate a t 1420-1395 cm-l and at 1230-1215 cm-'. The nuclear magnetic resonance spectra of the compounds indicated long-range c o ~ p l i n g ~of ~ the , ~ ~ fluorine with protons in the p position to the difluoramino groups.
2
For a-hydroxy ketones, the first step of the mechanism would be the reaction of difluoramine with the carbonyl group to give a substituted difluoramine-1,Z diol (3). This step involves the protonated ketone as the alkylating carbonium ion.24 Rhodesm reported a similar reaction of difluoramine with the carbon-oxygen double bonds of glyoxal which yielded 1,2-bis(difluoramino) -172-dihydroxyethane. The diol 3 is then esterified with sulfuric acid to form the cyclic sulfate 1. Cyclic sulfates are described in the literature26-n as being formed from the reaction of diols with fuming sulfuric acid. For a,b-diketones, the behavior would be similar to that of a-hydroxy ketones. After the reaction of difluoramine with the carbonyl groups, the diol 4 is esterified by sulfuric acid, forming the cyclic sulfate 2. The compounds prepared in this study proved to be stable under ambient conditions. However, they showed some sensitivity to mechanical shock. The structure of the new compounds was established by (23) R. C. Brasted, "Comprehensive Inorganic Chemistry." Vol. 8, Van Nostrand Co., Princeton, N. J., 1953, p 216. (24) W . H. Graham and J. P. Freeman, J . Amer. Chem. 8oc.. 89, 716 (1987). (25) C. M. Suter, "The Organic Chemistry of Sulfur," John Wiley & Sons,Inc., New York, N. Y., 1944. p 71. (26) J. Lichtenberger and R. Lichtenberger. Bull. Soe. Chim. Fr., 1002 (1948). (27) J. Brunken and E. J. Poppe, East German Patent 18,485 (1960); Chcm. AAstr., SS, 8296 (1961).
Warning: Precaution should be taken when handling difluoramine or difluoramino compounds because of their shock sensitivity. Reactions should be carried out behind proper shielding. General Procedure.-A 3-570 solution of difluorourea in methylene chloride and the carbonyl compound were placed ip a flask fitted with a dropping funnel, a thermometer, a Dry Ice reflux condenser, and an efficient stirrer. Fuming sulfuric acid (30y0 803) was dropped slowly into the reaction mixture a t such a rate that the temperature did not exceed 30". A white precipitate of ammonium hydrogen sulfate was formed, which later dissolved in the excess sulfuric acid. After all of the acid was added the stirring was continued for 5 hr. The entire reaction was carried out under nitrogen. The mixture was worked up by separating the methylene chloride layer, washing it with four portions of water (H20:CHrClZ, 1: 2 ) , and drying it over sodium sulfate. The solvent was then removed by distillation. The residue was distilled if the reaction product was a liquid; i t was recrystallized from methylene chloride (a-hexane) if the reaction product was a solid. 4- (3,3-Dinitrobutyl) -4-difluoramino-l,3-dioxa-2-thiolane2,2Dioxide.--A 5.31-g (25.8 mmol) sample of 2,2-dinitro+oxo-6hexanol and 7.20 g (75.0 mmol) of N,N-difluorurea in 150 ml of methylene chloride were allowed to react with 20 ml of fuming sulfuric acid (30% SOa). This reaction yielded 3.40 g (40%) of 4- (3,3-dinitrobutyl) -4-difluoramino-1,3-dioxa-2-thiolane2,2dioxide: mp 89-90"; ir (KBr), 830-1040 (NFt), 1215 and 1400 cm-l (SO,) ; nmr (GDsO), 6 5.28 (m, 2, C (NF,) CHZOSO,),2.99 (m, 2, C(NOz)2CHXH2),2.52 (m, 2, C ( N O Z ) ~ C H ~ C H 2.30 ~), (9, 3, CH3C (N0z)zCHr). Anal. Calcd for CeH9F2N30sS: C, 22.44; H, 2.82; F, 11.83; N, 13.08; S, 9.98. Found: C, 22.63; H, 2.62; F, 12.10; N, 12.86; s, 9.99. 4- (3,3,3-Trinitropropyl) -4-difluoramino-lI3-dioxa-2-thiolane 2,2-Dioxide.-A 1.90-g (8.0 mmol) sample of l,l,l-trinitro-40x045-pentanol and 19.21 g (200 mmol) of N,Ndifluorourea in 400 ml of methylene chloride were allowed to react with 50 ml of fuming sulfuric acid (30% so,). This reaction yielded 1.5 g (53y0) of 4- (3,3,3-trinitropropyl) -4-difluoramino-l.3-dioxa-2thiolane 2,a-dioxide: mp 86-87'; ir (KBr), 820-1040 (NFZ), 1225 and 1395 cm-l (SO*); nmr (C,D@), 6 5.31 (m, 2, C(NF2)CHzOS02),3.80 (m, 2, C(NOz)3CHzCH2), 2.83 (m, 2, C(N02)3CHrCHz). Anal. Calcd for CsHBF2NnOlaS:C, 17.05; H, 1.72; F, 10.79; N, 15.91;S, 9-10. Found: C, 17.29; H, 1.97; F, 10.75; N, 15.70; S, 9.36. 4,5-Dimethyl-4,5-bis (difluoramino) -1,3-dioxa-2-thiolane 2,2Dioxide.-A 2.58-g (30.0 mmol) sample of diacetyl and 7.59 g (79.0 mmol) of N,N-difluorourea in 155 ml of methylene chloride were allowed to react with 30 ml of fuming sulfuric acid (30% SO3). This reaction yielded 3.10 g (410j0) of 4,5-dimethyl-4,5bis (difluoramino)-1,3-dioxa-2-thiolane 2,2-dioxide: mp 43-44'; ir (KBr), 820-1010 (NF2), 1225 and 1420 cm-l (SO,); nmr (CDCh), 6 1.98 (m, 6, CH3). Anal. Calcd for C4HOF,N?OdS: C, 18.90; H, 2.38; F, 29.90; N, 11.02. Found: C, 18.89; H, 2.34; F, 30.59; N, 10.94. 4-Phenyl-4,5-bis (difluoramino) -5-methyl-l , 3-dioxa-2-thiolane 2,2-Dioxide.-A 4.74-g (32.0 mmol) sample of 1-phenyl-1,2dioxopropane and 8.07 g (84.0 mmol) of N,Ndifluorourea in 166 ml of methylene chloride were allowed to react with 25 ml of fuming sulfuric acid (30y0 SO*). This reaction yielded 4.40 g (43%) of 4-phenyl-4,5-bis (difluoramino)-5-methyl-l,3-dioxa-2thiolane 2,2-dioxide: bp 175-177" (1 mm) ; ir (neat), 820-1020 (28) A. H. Lewin, J . Amer. Chem. Soe., 86, 2303 (1964). (29) F. A. Johnson, C. Haney, and T. E. Stevens, J . Org. Chsm., 81, 466 (1967).
VoZ. 34, No. 4, April 1969
RING-CHAINTAUTOMERISM 919
(NF2), 1230 and 1420 cm-1 (SO2); nmr (CDCld, 6 7.35 (s, 5, C C H ~ 2.08 ) , (m, 3, CHs). A d . Calcd for Cd&FdN*08: c, 34.18; HJ 2.55; F, 24-03; N, 8.86. Found: C, 33.92; H, 3.01; F, 23.23; N, 8.77.
Registry No.-Difluoramine, 10405-27-3; sulfuric acid, 7664-93-9; 4-(3,3-dinitrobutyl)-4-difluoramino-
1,3diox~2-thiolane2,2-dioxide, 18963-41-2; 4-(3,3,3trinitropropyl)-4-difluoramino-ll3-dioxa-2-thiolane2,2dioxide, 1896342-3; 4,5-dimethyl-4,5-bis(difluoramino)-l,3dioxa-2-thiolane2,2dioxide, 18963-43-4; 4phenyl-4,5 -bis(difluoramino)-5-methyl- 1,3-dioxa- 2 thiolane 2,2-dioxide, 18963-44-5.
Ring-Chain Tautomerism of Imine-Amine or Ketone-Carbinol Systems Obtained by Condensation of Dilithio-N-Substituted Carboxamides or Sulfonamides with Benzonitrile. Synthesis of Cyclic Products' HAMAO WATANABE, CHUNG-LING MAO,I. T. BARNISH, AND CHARLES R. HAWSER Department of Chemistry, Duke University, Durham, hTorthCarolina 87706 Received September 16, 1968 Condensations of benzonitrile at the ortho position of N-substituted benzamides and N-substituted benzenesulfonamides were effected by means of n-butyllithium to form imine-amine, ring-chain tautomeric systems; in three of the four cases studied, the equilibrium was far on the side of the cyclic primary amines. All four of the primary amines were condensed with benzaldehyde to give corresponding benzal derivatives; also, the imine-amine product from N-methylbenzenesulfonamide and benzonitrile reacted with ethanol to give a cyclic ether-aulfonamide. The imine-amine, ring-chain products from the N-substituted benzenesulfonamides were hydrolyzed to afford ketone-carbinol, ring-chain systems, the equilibrium of which was far on the side of the ketone. Condensations of benzonitrile a t the %methyl group of N-substituted o-toluenesulfonamides were effected by means of n-butyllithium, and the resulting imines were hydrolyzed to give corresponding ketone-carbinol, ring-chain tautomeric systems. Although the equilibrium was on the side of the ketone, the cyclic carbinols were dehydrated to afford unsaturated cyclic sulfonamides, which are substituted benzothiazines. These double-bonded compounds underwent intramolecular @ elimination with alkali amides in liquid ammonia to form corresponding acetylenic sulfonamides. Several new types of products were synthesized.
Ketones having acidic groups at the ortho positions such as o-benzoylbenzoic acid2and o-benzoybenzanilide ( l y are known to exhibit ring-chain tautomerism. Thus, 1 is in equilibrium with carbinol amide 2 as evidenced by polarographic measurements and by reaction with methanol in the presence of acid to form ether amide 3.3 0
SCHEME I Li
Li
a C OC-NLi N R
I
0 1'0
e 2
RC0"
3
In the present investigation some new ring-chain systems involving imine-amine or ketone-carbinol tautomers were prepared and converted to certain new types of cyclic products. Tautomerisms Involving Five-Membered Rings.Dilithiocarboxamides 4a,b were condensed with benzonitrile to form the imine carboxamides 5a,b, which entered into equilibrium with the cyclic amine carboxamides 6a,b as evidenced by their condensations with benzaldehyde to give the benzal derivatives 7a,b, respectively; also cyclic amine 6b waa deaminated with nitrous acid to afford ketone 1 (Scheme I). The dilithioamides 4a,b were prepared by dilithiation of the (1) Supportad by the Army Research O5ce (Durham) and by Public Health Service Research Grant No. CA-04455 from the Natioml Cancer Institute. (2) P. R. Jones and P. J. Desio, J . Org. Chem., 80,4293 (1966). (3) 8. Wawsonek, H. A. Laitinen, and 9. J. Kwiatkowski, J . Amer. Cham. Soe., 68,830 (1944); see also P. R. Jones, Chem. Reu., 68,461 (1963).
C=NH
I
1
C6H5 5a, R = CH3 b, R = CcHs
C,H&HO ("0,
0
~
11 1 7a, R P CH3
b,
C$Is
corresponding N-substituted benzamides by means of n-butyllithium in tetrahydrofuran (THF)-hexane.* Interestingly, the equilibrium between the imines (4) See W. Puterbaugh and C. R. Haumr, J . Org. Chem., OS, 853 (1964).
