I252
Jolrrnal of the Aniericati Chemical Society
1
102:4
/ February 13, I980
Synthesis of Aliphatic Dimeric N-Isopropylhydroxamic Acids and the Crystal and Molecular Structure of N,N’-Dihydroxy-N,N’- diisopropylhexanediamide: A Hydroxamic Acid in the Trans Conformation William L. Smith and Kenneth N. Raymond* Contribution f r o m the Department of Chemistry and Materiols and Molecirlar Research Dicisioti. Lawrence Berkeley Laboratory, Utiicersity of Calijorniu, Berkeley, California 94720. Receiced Juij, 2, I979
Abstract: A series of dimeric N-isopropylhydroxamic acids, separated by (CH2)n units ( n = 4 , 6 , 8 . and IO), have been synthesized from the acid chlorides and N-isopropylhydroxylamine. The structure of the adipoyl derivative ( n = 4) has been determined from single-crystal X-ray diffraction data collected by counter methods. I n contrast to all previous hydroxamic acids that have been structurally characterized. the planar hydroxamate groups are trans, with C(O)-N and C=O distances similar to those found in amides. Strong intermolecular hydrogen bonds between the hydroxyl and carbonyl groups hold the molecules in pleated planes perpendicular to the b axis and compensate for the loss of the intramolecular hydrogen bond of the cis conformation. The intermolecular hydrogen bonds appear to be stronger than the intramolecular hydrogen bonds of the cis conformation, but the latter are entropically favored in solution. The molecules are located on a center of inversion in the space group Pbca with a = 9.3859 (3), b = 18.7156 ( 2 ) ,and c = 8.4180 (2) A. Full-matrix least-squares refinement on 1217 independent data with FO2> 3 0 ( F O 2 )and all atoms (including hydrogen) anisotropic led to an R factor of 3.8%.
Introduction As part of the development of actinide-specific chelating agents,’ a series of dimeric N-isopropylhydroxamic acids. which are connected by even-numbered carbon chains of four to ten, have been synthesized from the acid chlorides and N isopropylhydroxylamine. Unsubstituted dimeric hydroxamic acids separated by up to eight carbon atoms previously have been prepared from the esters and basic hydroxylamine.’ Acid chlorides are more reactive but require a N-substituted hydroxylamine to prevent the formation of cyclic N-diacylhydroxylamines. A series of dimeric N-phenylhydroxamic acids has been prepared from the acid chloride^,^ but the Nphenyl group may impart undesirable redox properties to the ligand as observed in the oxidation of U(lV) to the uranyl ion by N-phenylbenzohydroxamic acid.6 Because of the anomalously high melting point and extremely low carbonyl stretching frequency, the structure of N,N’-diisopropyladipohydroxamicacid ( I ) was of interest to us. Although no other structures of N-substituted hydroxamic acids are known, the planar trans conformation of the hydroxamic acid group found in 1 is seen only in iY-hydroxyurea; whose geometry is influenced by hydrogen bonding of the amino group. The structures of aceto-,8 benzo-,’ and salicyclo-Io hydroxamic acids and the 1R spectrum of formohydroxamic acid” show a planar cis conformation. This conformation is retained in the structures determined for a series of four 0-benzoylbenzohydroxamic acids.’’ Thus all solid-state structures of hydroxamic acids are cis, although the trans isomer is expected to be the more stable in the absence of intramolecular hydrogen bonding. In fact, reports of such isomerization have appeared for the related hydroximic acids R?-O
OH
I t
R,-C=N
for R1 = R? = CH3I3 and R l = Ph. R2 = Eti4,where no intramolecular hydrogen bonding is possible. With the expectation that perhaps the anomalous properties of compound 1 could be explained by such isomerization, the structure analysis reported here was begun, 0002-7863/80/ 1502- I 252$01 .00/0
Experimental Section Infrared spectra were obtained on a Perkin-Elmer 283 or a Beckman IR-9 spectrophotometer. ) H N M R spectra were recorded on a Varian EM 390 spectrophotometer. Melting points were determined in open capillaries with a Buchi apparatus and are uncorrected. Microanalyses were performed by the Analytical Services, Chemistry Department. University of California, Berkeley. The dicarboxylic acids, which were used as obtained, were converted into their acid chlorides by refluxing thionyl chloride followed by fractional vacuum distillation. ;~-lsopropylhydroxylarnine was prepared by the reduction of ?-nitropropane with zinc dust.‘5 N,N-Dihydroxy-.V,N’-diisopropylhexanediamide(1). A suspension of 0.22 mol of isopropylhydroxylamine and 0.3 mol of NaHCO3 i n 250 mL of ether and 25 mL of water was cooled to 0 O C and 0. I mol of adipoyl chloride. diluted with an equal volume of ether. was added dropwise with stirring. After stirring overnight. the reaction mixture was filtered and the precipitate was crbstallired from methanol. The resulting solid was washed with 25 mL of 0.01 M HCI followcd by 3 X 25 mL of water. These washings exhibited a positive FeC13 test indicating the presence of the nionohydroxaniic acid, probably formed by the hydrolysis of an eight-inembered cyclic .V.O-diacylhydroxylamine (see ref 2). Compound 1 was obtained as a w hite powder after recrystallization from methanol. Anal. Calcd for C12H&204: C. 55.36; H, 9.29; &, 10.76. Found: C, 55.26: H, 9.21: N, 10.67. N,N’-Dihydroxy-V,,V-diisopropyloctane-, -decane-, and -dodecanediamide (2-4). LJsing the above procedure, thebe compounds were obtained as white plates after recr)stalliting the first precipitate twice from methanol. Anal. Calcd Tor C 1 4 H ~ X N C, ~O 58.3 ~ : I ; H, 9.79: N,9.7 I . Found: C, 58.35; H, 9.78: N , 9.68. Anal. Calcd forC16H32N204: C. 60.73; H. 10.19; N,8.85. Found: C, 63.02: H . 9.98: R , 8.83. Anal. Calcd for C18H36N20j:c, 62.76: tl, 10.53; h’. 8.13. Found: C , 63.02; H, 10.17: N , 8.08. The yields and physicocheinical properties of the above hydroxamic acids are summarized in Table I. X-ray Diffraction Studies. Colorless rhombic needles of N,N’-diisopropqladipoh~droxarnicacid (1) were obtained by the slow evaporation of a methanol solution. A piece o f crystal of dimensions 0.1 8 X 0.23 X 0.38 mm was cleaved from a long needle using a scalpel and was sealed in a thin-ualled glass capillary. Precession photographs and diffraction data showed orthorhombic symmetry and the systematic absences Okl, k i2tr;h0/, I # 2n;hk0, h # 2n; consistent with the space group Phcu. Graphite-lnonochromatiled Cu Ktu riidiation was used for the precise measurement of the cell constants and
Smith, Raymond
/
A Hydroxamic Acid in the Trans Conformation
1253
Table I. Synthesis and Characterization of Aliphatic Dimeric N-lsopropylhydroxamic Acids
0
0
1I
II
ClC(CHJnCC1
n
mol wt
mp,OC
4 6 8 IO
260.3 288.4 316.4 344.5
162-163 135-136 137-138 138-139
(I
OH
1
OH 0
0
I II
NaHCO,
+ 2(CH&HNH 7 (CH&CHN-
1I
OH
I
C(CHJ,C-NCH(CHJ,
IH N M R (Me2CO-ds-Me4Si), 6, ppm ( J , Hz) IR, cm-' KBr pellet MeOH s o h (CH3)zC
