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Tetrahedron Letters 2001

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185 views4 pages

Tetrahedron Letters 2001

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Monika
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TETRAHEDRON LETTERS, Pergamon Tetrahedron Letters 42 (2001) 8519-8522 —— An unusual case of carbon-nitrogen bond formation. Reactivity of a C-nitroso group toward acyl chlorides Viktor Pilepié,* Monika Lovrek,* Drazen Vikié-Topié® and Stanko Ussie™* "Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovaciéa 1, 10000 Zagreb, Crostia "Rugier Boskovié Institute, NMR Center, PO Box 180, 10002 Zagreb, Croatia Received 3 August 2001; accepted 21 September 2001 Abstraet—Acyl chlorides react with nitrosobenzene in 99.9% acetonitrile and in the presence of catalytic amounts of HCI giving the corresponding N-p-chlorophenylhydroxamic acids. The spectroscopic and kinetic evidence obtained indicates that the reaction is initiated by the formation of an N-chlorohydroxylamine intermediate from nitrosobenzene and hydrochloride in the fist. slow step of the process. The nucleophilic V-chlorohydroxylamine intermediate reacts with acyl chloride (or possibly an acyl cation. chloride ion pair) to give the addition acylnitroso intermediate which undergoes to nucleophilic attack by chloride ion at the para position of the phenyl moiety and, after proton transfer from carbon, the corresponding N-p-chlorophenylhycroxamic acid is formed. © 2001 Elsevier Science Ltd, All rights reserved, Formation of a carbon-nitrogen bond is among the most important fundamental processes in organic chemistry and biochemistry. For example, many impor- tant chemical and biochemical processes are initiated by the addition of a nitrogen nucleophile to a carbonyl group.'? Recently, we have investigated a more sp case of the nucleophilic interaction of a C-nitroso group with the carbonyl group of some aldehydes and -0xo acids.”? The interactions involve the formation of a C-N bond, while the reaction products are hydrox- amie acids. The acids are of considerable importance due to their numerous industrial and pharmaceutical applications," We report here the surprising observation that acyl chlorides can interact with nitrasobenzene leading to Ai hyo oe Q or oO +l CN bond formation, where the corresponding N-p- chlorophenylhydroxamic acids are the products of the reaction (Scheme 1). This previously unknown reac- tion seems {0 be quite unexpected. Namely, the above mentioned formation of hydroxamie acids via the nucleophilic interaction of the C-nitroso group with the carbonyl group of aldehydes® and a-oxo acids™** involves heterolytic C-H or C-C bond cleav- ‘age (proton transfer from the carbon*? or decarboxylation) at the carbonyl group to give the electron pair needed for the final formation of the hydroxamie group. The possibility of such a heterolytic bond cleavage, however, does not exist in the case of acyl chiorides. Our observations are as follows: e ° geoH + 4 4 5 0, wrt \ho Cys } a ‘5 GY 1 2 3 Re cH. , -O. «a selene Keywords: C-nitroso group; acyl chlotides; hydroxamates: kinetics; mechanism. Corresponding author, Tol: +385-1-481-8306; fax: +385-1-485-6201; e-mail su nana, [Link] (040.4039)01/8 ~ see front matter © 2001 Elsevier Science Lid, All rights reserved PHI: S0040-4039(01)01812-3, 8520 V, Pllepé er ak, /Terabedion Letters 42 (2001) $319-8322 1. Acyl chlorides react with nitrosobenzene in 99.9% acetonitrile and in the presence of catalytic amounts, of HCI giving the corresponding N-p-chlorophenyl- hydroxamie acids (Scheme 1). Under the conditions employed in the kinetic investigation the reaction oes to completion, as shown spectroscopically (Fig. 1). The evidence is corroborated by the product analysis." The spectroscopic evidence does not sug- gest the accumulation of any intermediate in the reaction. In the absence of HCl, the reaction is negligibly slow. 2. The observed kinetics for the hydroxamic acid for- mation were of the first order with respect to the Figure 1. Change in the UV spectrum of the reaction mixture containing 0.0417 mol dm? CHCOCL, 10% mol dm-> CHO and 0.03 mol dm-* HCL in 99.9% acetonitrile, at 5.0°C. Seans (from A downward): 0, 5, 10, 15, 20, 25, 30, 35, 40, 45 and 160 min. The spectra of acetyl chloride were subtracted for clarity. the quoted hydroxamic acids were isolated and characterised using CHN analysis, NMR, IR and UV-vis spectroscopy. ‘The evidence obiainel was in sosordance with published data (see Ref 4). Thus, for example, for N-p-chlorophengleyclopropylhydroxamic acid we’ obtained: mp L14-117°C; elemental analysis caled. fr CyoHfCINOs C, $6.75: H. 4.76; N, 662: R, 31.87; found: C, 7.76; H.4.90; N, 668; R, 30.66% "HNMR (DMSO, 300 MH2)" 9 087 GH, d, J=8 He), 250 (IH, $), 741 GH, d, 4=9), 7.66 GH, , /=9), 10.84 (IH, 9, ""C NMR (DMSO, 360 Milz) 5 1728, 1409, 128, 128.3, 121.9, 113, 8.4 IR (KBr, em): 3100.6, 28939, 1617.9, 1487.2, 14304, 1338.1, 1315.6, 12926, 1085.5, 1068.2, 936.6, $282, 752.8 481.3; For -p-chlorophenyhicetobydroxamie acid we ‘bined: mp 72-79°C, elemental analysis caked for CyH,CINOy: C, S177; H, 4.34, N, 7.55; R, 3634; found: C, 51.63; Hy 442; N, 7.585, R, 36.27% 'H NMR (DMSO, 300 MHz): § 2.20 3H, 3), 7.39 QH, 4, J=9), 146 2H, d, J=9), 1069 (1H, 3, "C NMR (DMSO, 200 MH) 6 1703, M06, 131.7, 1284, 121 IR (KBr, ems 31359, 28044, 1623.6, 14859, 1381.4, 1095.8, 1013.6, 829.1, 78.3, 497-7, UV (MECN): yg =256 i, tg yg = 9984 mol! dt Traces of water (0.03%) were present in scatonitile which could lead to the very small amounts of HCI due to slow hydrolysis of acetyl chloride ee 00 005; 0.0, 015 [CH_COGH fmol dmv> Figure 2. The dependence of the ny, versus acetyl chloride concentration for the reaction of aceiyl chloride with nitro- sobenzene in 99.9% acetonitrile at 25.0°C. O: at 0031 mol dm-* of HCL @: at 0.150 mol dm” of HCI. Nitrosobenzene: 10- mol dm- (sce also Fig. 3 forthe remaining detail) 040 K,y 05 910, 045} {HC mol din 00! 0. [HCI] /mol dni? Figure 3. The dependence of the K./[HCI] versus HCI eon: centration for the reaction of acety chloride with nitrosoben: zene in 99.9% acetonitrile at 250°C. The observed rate ‘constants were determined spectrophotometrically by follow. ing the disappearance of the absorbance of nitrosobenzene at 305 nm (or by following the inerease in the absorbance at 256 ram) using a HIP 8452 or HP 8453 UV-vis spectrophotometer. Very good first-order kinetics within at least three halF-tives of the reaction were obtained. CH,COCI: 0,007 mol dm C\HGNO: 10 mol dmv; and 03 mol ém*. In order to avoid the use of aqueous HCl, a solution of dry gaseous HCI in 99,9% acetonitrile was used throughout. Inset: The depen: dence of the the ky, versus HCI anneentration for the reac tion of acetyl chloride with nitrosobenzene in 99.9% acetonitrile at 25.0°C, The reaction conditions were the same as described above. V, Plepié etal. /Tetratedron Letters 42 (2001) 8519-8522 8521 nitroso compound but did not depend on the con- centration of the acyl chloride (Fig. 2) (in the exper- iments, acyl chloride was always in great excess over the nitrosobenzene concentration). The result is the same regardless of the starting HCI concentration (see Fig. 2) and is consistent with the relatively fast interaction of acetyl chloride or acetyl cation-chlo- ride ion pair with a nucleophilic intermediate (see below) arising from nitrosobenzene and HCI in the preceding slow step of the reaction. 3. The dependence of the observed pseudo first-order rate constants on hydrochloride concentration (Fig, 3) is complex and is consistent with the rate law a 4, The values of the parameters ky and ky are 0.0167 s! mol! dm’ and 0.140 s"' mol” dm, respectively. The observed linear term of Eq. (I) requires that the interaction of nitrosobenzene with a single H°CI- ion pair! can lead to the reactive intermediate which we describe as N-chlorohydroxylamine (2). There are a large number of addition reactions of the C-nitroso group where the nitroso group acts as an electrophile and the addition of anionic nucleophiles to the nitroso group to give transient intermediates is not unknown! In addition, chloride is in a polar, aprotic solvent such as acetonitrile is strongly desol- vated which makes it more basic’ and more capable of addition to a nitroso group. The same intermedi- ate can, of course, arise from the interaction of two hydrochloride ion pairs with the nitroso group which corresponds to the quadratic term of Eq. (1). This term could also be consistent with the forma- tion of an alternative, 4-chlorohexadienone oxime intermediate 2a. However, only a minor contribution of that inter- mediate to the overall process is expected, due to its greater basicity (and subsequent protonation) in comparison to N-chlorohydroxylamine!! On. the other hand, the change in the spectra of the reac- tants and products during the course of the reaction remained the same when 0.15 M of water was added to the reaction mixture. Taking into account. that nitrosobenzene is a relatively weak nucleophile, it seems highly unlikely that, under the conditions employed in the kinetic experiments (10 M of nitroso compound), nitrosobenzene alone could compete with water (being in 1500-fold excess over “Our conductimetric measurements indicate that HCI shoud be present in 99.9% acetonitrile (used in all the experiments), excl sively, inthe form of an ion pair (or possibly hydrogen-bonded ion pit) whilst the measurements suggest that benzsltrinethylammo sium chloride i (in the same solvent) substantially dissociated ‘Por example, the pX, of HCL in unother polar aprotic solvent,

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