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(1968). (44) . . P. S.Bailev. J. E. Keller. D. A. Mitchard, and H. M. White. Adv. Chem. Ser., 77, 58 (1968). (45) F. E. Stary, D. E. Emge, and R. W. Murray, J. Am. Chem. SOC.,98, 1880 l l.D- 7. A I _,. (46) F. KovaE and 8. PlesniEar, J. Chem. SOC., Chem. Commun., 122 (1978). (47) F. KovaE. and B. Plesniear, J. Am. Chem. Soc., 101, 2677 (1979). They observed singlet 0 2 yields by chemical scavenging. (48) (a)M. E. Kurz and W. A. Pryor, TetrahedronLett., 697 (1978);(b) J. Am. Chem. SOC., 100,7953 (1978). (49) Reference 16b, Chapter XV, p 400. (50) R. F. Hampson. Jr., and D. Garvin, Eds., “Reaction Rate Data and Photochemical Data for Atmospheric Chemisby-l977”, Natl. Bur. Stand.(U.S.), Spec. Pub/., No. 513 (1978). (51) The 0-atom steady-state concentration could not exceed [O],,IKeq [ ( 0 3 ) / ( 0 2 B ]where , Keqis for the dissociation reaction (VI) and is e ual to 104~8-24’ M49 and 0 = 2.303RTkcal/mol. At 300 K [O],.I10-q0.7 M, so that the half-life of a typical RH mi ht be -5 days for 0 3 / 0 2 ratios of about 4%. At -78 “C, [O],,I10-2QMand any R H reaction is immeasurably slow. (52) S.W. Benson, Adv. Chem. Ser., No. 77, 74 (1968). ~
(53) S.W. Benson, J. Chem. Phys., 34, 521 (1961). (54) S. W. Benson, Adv. Photochem., 2, l(1964). (55) S.W. Benson and W. 8. DeMore, Annu. Rev. Phys. Chem., 18, 397 (1965). (56) R. C. Dobson, D. M. Hayes, and R. Hoffman, J. Am. Chem. Soc., 93,6188 (1971). (57) S. W. Benson and A. N. Bose, J. Chem. Phys., 37,2935 (1962). See also S.W. Benson and G. R. Haugen, J. Am. Chem. SOC.,87,4036 (1965); J. Phys. Chem., 70, 3336 (1966): 71, 1735 (1967). It is shown in the above that additional attraction due to mutual polarization is nearly canceled ( f 2 kcal) by a repulsion term (Born type). (58) “Tables of Interatomic Distances,” Chem. Soc., Spec. Pub/., No. 11 (1958). (59) J. G. Kirkwood, J. Chem. Phys., 2, 351 (1934);see also ref 16b, p 534. (60) S. W. Benson and R. Shaw, “Organic Peroxides”, Vol. I , D. Swern, Ed., Wiley, New York, 1970, Chapter 2. (61) F. Buckley and A. A. hhyott, “Tables of Dielectric Dispersion Data for Pure Liquids and Dilute Solutions,” Natl. Bur. Stand. (U.S.), Circ., No. 589 (1958). (62) J. H. Rytting, B. D. Anderson, and T. Higuchi, J. Phys. Chem., 82, 2240 (1978); G. Brink and L. Glasser, ibid., 82, 1000 (1978). (63) S. W. Benson and P. S. Nangia. unpublished work.
Gas-Phase Acid-Induced Nucleophilic Displacement Reactions. Stereochemistry of Inter- and Intramolecular Substitutions at Saturated Carbon] Maurizio Speranza” and Giancarlo Angelini Contribution from the Laboratorio di Chimica Nucleare del C.N.R.. Area della Ricerca di Roma, C.P. 10-00016 Monterotondo Stazione, Rome, Italy Receiued March 14, 1979
Abstract: The stereochemistry of gas-phase nucleophilic displacement by water on a number of positively charged intermedi-
ates was investigated under different experimental conditions. The ionic intermediates were generated in the gas phase a t atmospheric pressure by attack of radiolytically formed Bransted (CH5+, C2H5+) and Lewis [C2H5+, CHsFCH3+) acids on selected mono- and bifunctional substrates. Isolation and identification of their neutral substituted products allowed us to demonstrate that, under the used experimental conditions, gas-phase acid-induced inter- and intramolecular nucleophilic displacement reactions occur via predominant (64-98%) inwrsion of configuration a t the reaction center. The yield and the stereoisomeric distribution of the substituted products were found to depend on either the nature of the gaseous acid used to generate the charged intermediates or the concentration of the added base (NH3 or H2O). Product distribution from bifunctional substrates is characterized by the presence of minor amounts of substituted derivatives retaining the original configuration of their neutral precursors. Their formation is ascribed to the occurrence of an extensive neighboring group participation effect [an HO-3 process) on the displacement reaction, resulting in a double inuersion of the reaction centers. A mechanistic model is proposed for gas-phase nucleophilic substitutions at atmospheric pressures, and compared with those from related low-pressure ICR (ion cyclotron resonance mass spectrometry) and solution-chemistry studies.
Introduction One of the most serious limitations of the mechanistic studies of gas-phase ion-molecule reactions is the almost complete lack of information on the stereochemistry of the processes investigated and the identities of their neutral products. The sporadic application of different experimental techniques, whose common features are the isolation of the neutral products and the determination of their structure, only scratched the surface of this problem. An interesting contribution was provided by a sophisticated trapped-ion ICR experiment carried out by Lieder and Brauman,* who elucidated the stereochemistry of a single negative-ion displacement reaction via the detection of the neutral products. However, this powerful technique, as well as other mass-spectrometric approaches, has left many other stereochemical questions unanswered, as demonstrated by the limited number of ion-molecule reaction mechanisms investigated and by the rarity of unambiguous data concerning their stereochemistry. A typical case is represented by the proton-induced nucleophilic displacement reactions at saturated carbon, a process frequently observed in mass spec0002-7863/80/1502-3 1 15$01 .OO/O
trometry3 (Nu: = nucleophile, X = n-donor center, R = alkyl group). As to the mechanism, it is still uncertain whether process (1) involves direct intermolecular substitution (2a),4 Nu
+
t
RXH
-
NuR
* +
(1)
XH
i.e., a process corresponding exactly to the s N 2 type of solution chemistry (Walden inversion), or instead the more complex pathway (2b), leading to the retained substituted product via
r
l+
J
L
1~~1 (1)
-+
*tpx
4
Nu
+ %H/ :-
---C
Nu---- H
*\
+
+ xH
(2b)
Journal of the American Chemical Society
31 16
1 I02:9 1 April 23, 1980
Table I. Product Yields from the Gas-Phase Attack of Brqnsted and Lewis Acids on Monofunctional Substrates system composition substrate CH4, CH3F, (Torr) Torr Torr 760 760 760 760
trans-1 (0.7) cis-1 (1.4)
cis-2 (0.4) cis-2 (0.7) cis-2 (0.3) cis-2 (0.8) trans-3 (0.4) trans-3 (0.9) trans-3 (0.6) trans-3 (0.6)
760 760 760 760 760 760
product yields meso or cis G ( M ) ~ re1 x 102 70
H20, Torr
products
2.5 3.6 4.0 0.9 3.0 0.6 4.0 1.2 6.0 0.8
2,3-butanediols 2,3-butanediols 4-Me-cyclohexanols 4-Me-cyclohexanols 4-Me-cyclohexanols 4-Me-cyclohexanols 3-Me-cyclohexanols 3-Me-cyclohexanols 3-Me-cyclohexanols 3-Me-cvclohexanols
30.0 0.7 0.1 3.2 0.05 0.3 0.6 2.9 0.2 0.4
98 3 33 25 20 11 67 64 67 67
dl or trans G(M\ re1 x IO 70 0.7 26.7 0.2 9.6 0.2 2.4 0.3 1.6
0.1 0.2
2 97 67 75 80 89 33 36 33 33
inversion/ retention ratio 42.9 38.1 2.0 3.0 4.0 8.0 2.0 1.8 2.0 2.0
total absolute yield," % 11.4 10.1 0.1 4.6 0.3 1.6
a 02: 4 Torr. Radiation dose: 4.8 Mrad (dose rate: 0.4 Mrad h-I). G(M)as the number of molecules M produced per 100 eV of absorbed ) 1.9 0.2 and G ( c ~ H ~=+ )0.9 f 0.2 (ref energy. Standard deviation of data ca. 10%. Total absolute yields; estimated using G ( c H ~ += 1 2c).
*
Recently, the stereochemical features of two classes of gas-phase ionic processes, the bimolecular electrophilic substitutions8 and the cyclization reaction^,^ have been successfully investigated using radiolyticI0 and nuclear-decay' methods. In contrast with the classical mass-spectrometric approach, both techniques, in fact, are specifically designed to extend to gas-phase ionic process the methodology typical of solution chemistry, based inter alia on the actual isolation and identification of the neutral products. We, therefore, decided to apply one of these methods to the study of the stereochemistry of process 1 in order to assess the relative importance of the mechanisms 2a and 2b in the nucleophilic substitution reactions. To this end, we selected a set of gaseous acids (GA+ = CH5+, C2H5+, and CH3FCH3+), which can be conveniently produced in known yields by y-radiolysis of the appropriate neutral precursor (CH4 or CH3F).l2 Their attack on the n-donor center (X) of the following neutral substrates R X is expected to generate the corresponding X-protonated,
H
x = Cl H
C HOCH
I
X
X
-CH CH3
1
x
F
( A ) ;C I
( a ) ;Br (.$,I
OH
-ethylated, or -methylated derivatives (henceforth symbolized as [RXA]+), wherein the potential leaving group XA can be easily displaced by a suitable nucleophile (H20): (3)
The B r p t e d or Lewis-acid character of GA+ determines the nature of the moiety A in [RXA]+ and consequently its tendency of establishing with the incoming H 2 0 the intense electrostatic interaction required to form the complex II.I3 Finally, the structural features of the selected mono- (1-3) and bifunctional (4-6) substrates R X may help to elucidate the stereochemistry of inter- and intramolecular nucleophilic
substitutions and their relative extent in the bifunctional intermediates. Thus, special attention was devoted in picking out monofunctional substrates (1-3), wherein the influence of undesired effects (neighboring-group participation, steric hindrance, conformational shielding, etc.) on the stereochemistry of the displacement process is minimized.
Experimental Section Materials. Methane, methyl fluoride, oxygen, and ammonia were high-purity gases from Matheson Co., used without further purification. cis- and frans-2,3-epoxybutanes, meso- and dl-2,3-butanediols, and the other standards used were research-grade chemicals from Fluka A.G. Isomeric 4- (or 3-) chloro- I methylcyclohexanes (cis and trans) were prepared from a mixture of cis- and trans-4- (or 3-) methylcyclohexanols (Hoechst AG) by chlorination with PC1si4 and purified by preparative GLC, and their identity was checked by N M R analysis.i5 Addition of hypohalogenous acid on the appropriate isomeric 2-butenes afforded the relative halohydrins in good yields.I6 3-Fluorobutan-2-01 isomers were prepared by F-to-CI displacement from anhydrous K F on the appropriate ~ h l o r o h y d r i n .Each ' ~ pair of isomeric halohydrins (erythro and threo forms) was resolved and purified by preparative G L C (5-m 25% Silicone Oil E 301 on Chromosorb W 60-80 mesh, T , 75 (F), 100 (CI), 145 O C (Br)), and their identity checked by N M R analysis. All the starting substrates were repeatedly purified and their purity was checked by GLC, using flame ionization detection (FID). Procedure. The gaseous mixtures were prepared by conventional techniques, using a greaseless vacuum line. The reagents and the additives were introduced into carefully outgassed 1 -L Pyrex bulbs, each equipped with a break-seal tip. The bulbs were filled with I atm of the appropriate bulk gas (CH4 or CH,F), cooled to the liquid-nitrogen temperature, and sealed off. The irradiations were carried out a t a temperature of 37.5 "C in a 220 Gammacell from Nuclear Canada Ltd., at a dose rate of 0.4 Mrad h-I, as determined by a Fricke dosimeter. Analyses of the irradiation products were accomplished by injecting known aliquots of the homogeneous gaseous system into a Hewlett-Packard Model 5700 A gas chromatograph, equipped with a FID unit, and their yields determined from the areas of the corresponding eluted peaks, using individual calibration factors.
Results Table I reports the G ( M )values of the products formed from the monofunctional substrates (1-3) undergoing gas-phase attack from the radiolytically produced acids, in the presence of water as the nucleophile (eq 3). The data concerning the irradiation of the gaseous mixtures containing the bifunctional substrates (4-6) are listed in Table 11. The reported results were obtained at a constant dose of 4.8 Mrad (dose rate 0.4 Mrad h-'), and represent the mean values from several separate irradiations carried out under the same conditions. The standard deviation is of the order of 10% except for the lowest values, characterized by a somewhat lower precision. The product yields depend on the composition of the gaseous mixture and,
Speranza, Angelini
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Acid-Induced Nucleophilic Displacement Reactions
Table 11. Product Yields from the Gas-Phase Attack of C,Hs+ ( n = 1.2) Ions on Bifunctional Substrates ~~~
~
~~~
~
system composition" substrate CH4, H20, (Torr) Torr Torr erythro-4 (2.0) threo-4 (2.0) erythro-5 (2.0) erythro-5 (1.6) erythro-5 (2.3) erythro-5 (1.4) threo-5 (2.0) threo-5 (2.0) threo-5 (1.5) threo-5 (1.6) erythro-6 (1.9) threo-6 (2.0)
760 760 760 760
Torr
11.2 (12)
0.9
3.0 10.0 1.9 0.9 3.0 10.0
760
760 760
1.8
760
1.9
(re1 %)
90.4 (93)
2.2 2.1 1.9
760
760 760 760
NH3,
G(M) X lo2 values of productsb 2,3-butanediols inversion/ meso dl retention (re1 %) (re1 %) ratio (re1 %)
total inversion/ absolute retention yields,c ratio %
2,3-epoxybutanes trans cis
42.4 (89) 79.4 (92) 76.3 (84) 37.9 (87) 4.0 (9) 5.2 (14) 4.0 (20) 2.5 ( I 1) n.d. n.d.
7.2 (7) 86.0 (88) 5.2 (1 1) 7.2 (8) 14.9 (16) 5.9 (13) 39.0 (91) 33.2 (86) 16.5 (80) 19.7 (89) n.d. n.d.
12.6
7.7 8.1 11.0
2.4 (73) 0.6 (22) 0.3 (>97) n.d.
0.9 (27) 2.1 (78) n.d.d (
