Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups / 0909 110

17. Syntheses and uses of isotopically labelled compounds

1029

KIE is consistent with a polar, PL, mechanism, and with an ET RC-mechanism with partial rate-determining RC. The supplementary experiments led the authors421 to the conclusion that the reaction 222 is realized through the polar nucleophilic mechanism. No supplementary evidence was obtained for electron transfer during the reaction. The small

but positive 14C KIE (k12/k14 D 1.012 š 0.006, D 0.16 š 0.06) was observed in the reaction with benzaldehyde (equation 223) and interpreted also proceeding likely through

the polar mechanism. An early and six-membered TS has been proposed for reaction 223 with benzaldehyde, occurring for steric reasons 9 times faster than the reaction 222 with benzophenone.

Ph 14 C

Ph + CH

CHCH I

Zn / THF

Ph2 14 C(OH)CH2 CH

CH2

2

2

25

° C

(222)

O

Ph14 CHO

+

Zn / THF

Ph14 CH(OH)CH CH

CH

(223)

CH2

CHCH2 I

2

2

14. 14C KIE in the Wittig reaction of benzophenone(carbonyl-14C) with isopropy/idenetriphenylphosphorane

According to 31P-NMR studies424,425 the Wittig reaction426 proceeds as shown in equation 224 in which the cyclohexanone and ethylidenetriphenylphosphorane give rapid formation of oxaphosphetane followed by its slow decomposition into phosphine oxide and alkene. The 14C KIE in the title reaction has been found to be equal to 1.053 š 0.002. This value clearly indicates that the bonding at the carbonyl carbon is changing in the ratedetermining step (RDS) of the reaction and is consistent with a mechanism in which the RDS is the direct formation of oxaphosphetane, although the decomposition of the latter may also be rate-limiting425. The authors425 admit that the formation and decomposition of oxaphosphetane may have similar TS characteristics and both steps may give similar KIE. To clarify this point further studies have been considered. A statement has been also made that the ET is the RDS in reaction with benzaldehyde, while C C formation (because of steric hindrance) and oxaphosphetane formation become the slower RDS for

the ketone.					Ph3 P	O
	R1	R3
							k3
Ph3 P C	+	14 C O	k1		R1 C	14 C R3		Ph3 P		O
			k	2
	R2
		R4			R2	R4
					(377)		R1		R3
						+		C 14 C
							R2		R4

(224)

In view of the ambiguity involved in the detailed model calculations and lack of data concerning temperature dependences of the 14C KIEs presented in this part of the chapter, the numerical values of 14C KIEs collected in Table 2 and 3 should be given also the alternative simple interpretation which could be verified by determination of the 14C KIE for 14C-labelled, ylides and by 14C KIE temperature-dependence study.

In the course of formation of the relatively stable or fast decomposing 377 (equation 224) the [14C]-carbonyl double bond is transformed into a single [14C]- carbon oxygen bond, if the P O bond formation in TS is much more advanced than

1030		Mieczysław Ziełinski´ and Marianna Kanska´
	TABLE 3. Carbonyl- 14C KIE in the Wittig reactions in THF solvent
	Substrate	Ylide	exp. conditions (0 °C)		k12/k14
	PhCHO	Ph3PDCMe2	Li salt free (0 °C)		1.003 š 0.002
		Ph3PDCHPr	Li salt present (0 °C)		0.971 š 0.004
			Li salt free (0 °C)		0.998 š 0.002
			°		0.995 š 0.003
			Li salt present (0° C)
	Ph2CDO	Ph3PDCMe2	Li salt free ( 78 aC)		0.993 š 0.003
			Li salt free (0 °C)	a	1.053 š 0.002
		Ph3PDCHPh	Li salt present 0 °C		1.041 š 0.010
	PhCHO		Li salt free (0 °C)		1.060 š 0.003
			Li salt present (0 °C)		1.015 š 0.004

a In Et2O.

12C 14C bond formation, or into two single bonds, 14C O and 12C 14C, in the case of four-centered oxaphosphetane-like TS. Neglecting the contribution from rotation of both reactants and TS in the liquid phase and considering only carbonyl bond vibration in the substrates [ω 12CD16O D 1750 cm 1, ω 14CD16O D 1676.96 cm 1] and taking values ω 12C 16O D 1093 cm 1, ω 14C 16O D 1047.4 cm 1, ω 12C 12C D 900 cm 1

and ω 14C 12C D 867.22 cm 1 for vibration of the single C O and C C isotopic bonds in TS, we obtain in the ‘sinh’ approximation427 429 the (k12/k14) values for the oxaphosphetane-formation step equal to 1.067 (at 25 °C) and 1.074 (at 0 °C) for TS with far more advanced P O bond formation, and values of (k12/k14) equal to 0.9838 (at 25 °C) and 0.9835 (at 0 °C) for four-centered oxaphoshetane-like TS. The above brief calculations indicate that in the reactions of benzaldehyde with non-stabilized ylides, the formation of 377 determines in general the observed 14C kinetic fractionation in the overall Wittig reaction. The very instructive 14C KIE in the first-order decomposition of the oxaphosphetane derived from Ph14CHO and Ph3PDCMe2 have not been listed by Yamataka and coworkers425. The 14C KIEs observed in sterically hindered reactants (benzophenone, semistabilized and stabilized ylides) are reproduced by advanced P O bond formation TS. Full solution of the TS structure requires the 14C-ylide and 18O- carbonyl KIE determinations in Wittig reactions. The 14C KIEs in the Wittig reactions described adequately by equation 224 should depend on the k3/k2 ratio and on the degree of 14C 18O bond rupture and on the degree of 14CD12C double-bond formation in the TS of the overall reaction. The full vibrational analysis of oxaphosphetanes is required. The small value suggests that the TS is non-polar in the oxaphosphetane decomposition step.

15. Carbonyl KIE in the Wittig reaction of benzaldehydes with benzylidenetriphenylphosphoranes

The carbonyl- 14C KIEs in the title reaction system (equation 225), which gives a nearly 50 : 50 mixture of cis trans isomers, depends very much on the ylide used430, and indicate that the reactions proceed via cycloaddition TS of considerable nucleophilic character, inferred also from the substituent effects studied. Positive values indicate that the Wittig reaction is nucleophilic in nature. Assuming as before the four-centered TS, the authors430 conclude that the C C bond formation is much advanced of the P O bond formation in the TS and that ‘the carbonyl-carbon KIE are expected to be larger for later TS’ salt-free reaction410 (more reactant-like for Li salt present in reaction).

17. Syntheses and uses of isotopically labelled compounds

1031

16. Carbonyl-14C KIE in the Wittig reaction of non-stabilized ylides with benzaldehyde and benzophenone

The carbonyl 14C KIEs in the reaction of benzaldehyde with non-stabilized ylides have been found to be very small432 in contrast to the reactions of benzophenone, and taken as an indication of mechanistic differences between aldehydes and ketones. The numerical values of the 14C KIE collected in Table 3 have been interpreted within the reaction scheme shown in equation 224 and 226. The authors final conclusion432, influenced also by previous model calculation433, was that the non-stabilized ylide has enough ability to transfer an electron to benzaldehyde and benzophenone, and the Wittig reaction proceeds via initial electron transfer from ylide to carbonyl compounds. The electron transfer is the RDS for benzaldehyde while the radical coupling, RC, following the electron transfer step, is rate-determining432 for benzophenone. The reactions of semi-stabilized ylides proceed through the polar nucleophilic addition mechanism.

					H	C6 H4 R2
R1 C6 H4	14 CHO + Ph3 P		CHC6 H4 R2	THF		14
						C C
				0° C
					R1 C6 H4	H

(225)

		H	H
	+	14
		C	C
		R1 C6 H4	C6 H4 R2

≠

			C		O
	PL				+
				−
C O +	RM		R		M
	.				−
			C				RC
					O
					+ .
			R		M

(225)

− + (226)

C O M R

17. Brief review of KIEs in chemical reactions

Deuterium KIE in the reaction of 3-metyl-1-butene, 378, with CF3COOH-D (TFA-D), providing 3-methyl and 2-methylbutyl trifluoroacetate, 389, in about 53:47 ratio both in TFA-H and in TFA-D, was 6.8 (at 26.5 °C)434. In the similar reaction with 2-methyl-1- butene 379, and 2-methyl-2-butene, 380, with TFA-D, the D KIEs have been found434 to be 5 (379, 18 °C). and 3.9 (380, 18 °C). 378 reacts by carbocationic mechanism and undergoes a Me shift. Extensive H/D exchange between the solvent and the ester 381 took place.

The deuterium KIE of 2.5 š 0.1, observed at 297 K in the cleavage of tributyltin allylsulphinate with [2H]TFA in toluene435 (equation 227) has been interpreted as suggesting a rigid compact and ‘reactant-like’ early TS, and as confirming the concerted retro-ene mechanism of thermal desulphination of allylsulphinic acid (equation 228). The mechanism of hydroxyl radical-induced decarboxylation of 2-(alkylthio)ethanoic acid

1032	Mieczysław Ziełinski´ and Marianna Kanska´

derivatives has been investigated436 in H2O and D2O.

OSnBu3	+			O
			S
S	TFA					+ SO2 (227)
O			O
		H				Η
OH
S			+	(228)
				SO2
O	H

Deuterium KIEs in the oxidation of C6H6/C6D6, C6H5Me/C6D5Me, C6H5Me/C6H5CD3, 1,3-Me2C6H4/1,3-(CD3)2C6D4, 1,4-Me2C6H4/1,4-(CD3)2C6D4 with permanganate in aqueous solution437 have been found to be 1.0, 1.0, 13.6, 11.3, 16.8, respectively, at 70 °C. In the case of the C6H5Me/C6D5CD3 system, D KIE decreased from 16.4 at 50 °C to 10.8 at 90 °C. D KIE in the oxidation of alkylbenzenes with HMnO4 has been studied also. KIE k0H/k0D D 1.45 š 0.09, corresponding to oxidation with HMnO4, has been observed in the oxidation of toluene/toluene-D8 in KMnO4 H2O solutions under conditions of varying acidity438.

D KIEs proved439 that in the oxidation of formaldehyde on a polycrystalline platinum electrode modified with Pb atoms and on pure platinum electrode, the cleavage of both OH and CH bonds and the abstraction of the hydrogen atom from an OH bond in hydrated formaldehyde are rate-determining on the Pt/Pb and on the Pt electrode, respectively. The kH/kD for the oxidation of formaldehyde at copper electrode (at pH 13, at 25 °C) depends on the electrode potential and reaches the highest value of 7 at low potentials and drops to about 2.5 at higher positive potentials440.

The KIE in the oxidation of selectively deuteriated aliphatic alcohols (2-propanol, 1,2-butanediol, 1,4-butanediol and 2,3-butanediol) at a polycrystalline gold electrode in alkaline solutions with cyclic voltametry have been determined and discussed441. Isotope effects in the electrochemical reduction of deuteriated oxalic and benzoic acids at Pb cathodes in deuteriated media have been determined442. DOOCCOOD in D2O provided deuteriated glyoxylic acid but the large isotope effect of 5.3 found in this reaction leads to significant depletion of D in the aldehyde group. D KIE of 2.4 has been found in reduction of PhCOOD to PhCD2OD. The unlabelled PhCH2OH has been obtained in CD3OH/dil. H2SO4 medium. No incorporation of D into the aromatic nucleus has been observed.

D KIE of 6.35 has been observed in the oxidation of ˛-deuteriomandelic acid by pyridinium bromochromate to the corresponding oxo acid. The analysis of the D KIE indicated that the reaction involves a symmetric transition state443. The oxidations of phosphinic and phosphorous acids by pyridinium bromochromate exhibits a substantial primary deuterium KIE444. The hydroxyacids, glycolic, lactic, mandelic and malic acids are oxidized by pyridinium hydrobromide perbromide in acetic acid water mixtures to oxo acids445. The primary KIE in the oxidation of ˛-deuteriomandelic acid is kH/kD D 5.07, and it does not exhibit a solvent isotope effect. A mechanism involving hydride ion transfer to the oxidant has been proposed445.

The oxidation of primary aliphatic alcohols by bis(2,20-bipyridyl)copper(ll) permanganate (BBCP) in aqueous acetic acid leads to the formation of the corresponding aldehydes446. The oxidation of [1,1-2H2]ethanol exhibited446 a kH/kD of 4.50. The formation constants for BBCP alcohol complexes and the rates of their decomposition have been evaluated. Aliphatic aldehydes are oxidized by pyridinium hydrobromide

17. Syntheses and uses of isotopically labelled compounds

1033

perbromide to carboxylic acid447. Michaelis Menton type kinetics with respect to aldehydes are observed; Ł D 1.85 at 298 K points to an electron-deficient carbon centre in the TS and hydride ion transfer. A substantial D KIE indicates that the aldehydic C H bond is cleaved in the rate-determining step447. The kinetics of oxidation of 2-propanol, 2-butanol and 2-pentanol by pyridinium fluorochromate has been studied. The D isotope effect of 3.2 observed with 2-propanol indicated that the C H bond is broken in the RDS448. The oxidation of benzaldehydes by pyridinium fluorochromate has been studied also and a mechanism involving a complex between hydrated aldehyde and protonated oxidant has been suggested449.

A DIE of kH2O/kD2O D 3.2 has been found in the hydrolysis of ˛-benzoyloxystyrenes,

382, in concentrated perchloric acid solution450. The rate of hydrolysis was found to be linear with the acidity function, H0. A small inverse deuterium KIE, kH/kD D 0.78, at the ˛-carbon has been found in the oxidation of cinnamic and crotonic acids451 by quinolinium dichromate. The reaction involves electrophilic attack on the double bond and a carbonium-ion intermediate ( D 4.0). A small inverse D KIE [ kH/kD D 0.80,D 4.0] has been also observed452 in the acid cleavage of substituted styrenes by quinolinium dichromate in DMF in the presence of acid452.

C6 H4 R

H2 C C OCPh

O

(382) R = Me, H, Cl, NO2 , substituent effect ρ = −1.60

Values of kH/kD D 3.87 and kH2O/kD2O D 0.912 have been observed453 in the alkaline oxidation of allyl, crotyl and propargyl alcohols by monoperiodate complex of trivalent

copper453. Deuteriation of the vitamin E model compound 2,2,5,7,8-pentamethylchroman- 6-ol 383 at C5a454 inhibits its oxidation and favors the formation of 384. The products of

˛-tocopherol 385 oxidation in biological membranes have been identified454. TS structures and KIEs for the Claisen rearrangement of chorismic acid, 386, have been computed and compared with the experimental measurements455.

Inverse secondary KIEs, kH/kD < 1.0, have been observed in the reaction of Y-benzoyl, Y-benzenesulphonyl and Y-benzyl halides with deuteriated X-anilines in acetonitrile456, and their variations with substituents X and Y investigated. The smallest inverse solvent kinetic isotope effects (SKIEs) have has been found in the reaction of deuteriated aniline nucleophiles with benzoyl fluoride, reflecting the tight TS for this compound. The large SKIE of 2.1 2.9 have been found457 in a reaction of a series of 19 ring-substituted benzyl aldehydes with propylamine in CH3OD. A mechanism involving ˛-amino alcohol formation in the fast pre-equilibrium followed by the rate-limiting OH detachment providing iminium ions has been proposed457. Deuterium solvent isotope effects in the acid-catalyzed hydrolysis of N-phenyl-4-substituted benzohydroxamic acids, 4-XC6H4CON(OH)Ph(X D H, Me, OMe, NO2, Cl, F), in sulphuric acid solutions, have been found458 to be compatible with a changeover from an A-2 mechanism at low acidities to a A-1 mechanism at high acidity.

Improved yields of products have been achieved from oxidative free-radical cyclization of deuteriated substrates459, The reaction of CH2DCMeCH2CH2COCD(COOMe)CH2 CHDCH2 (387) with Mn(OAc)3 afforded 65% 388 (R1R2 D H, Me) whereas 387 of natural isotopic composition provided only 22% of 388 under the same conditions. Large

1034	Mieczysław Ziełinski´ and Marianna Kanska´
		Me
Me	Me	Me
		O
Me O		O	α-tocopherol,
			C2 9 H50 O2 (385)

Me

Me

O Me

(384)

COOH

CH2

O COOH

OH

(386)

KIEs change the nature of the termination step and prevent the formation of acyclic radical

ž

CH2DCMeCH2CH2COC(COOMe)CH2CHDCH2 (389) by internal hydrogen transfer.

O

COOMe

Me

R	1	R2
		(388)

The primary kinetic H/D isotope effects in the syn elimination of HX from CH3CH2X (where X D H, BH2, Me, NH2, NH3C , OH, OH2C , F, Cl and Br) producing C2H4-HX complexes have been examined theoretically460 Four-centered TS structures are found for all but X D H, BH2 and Me (for H and Me three-centered TS are predicted). The primary KIE increases systematically as the central atom of X varies from left to right along a row or down a column of the periodic table and as X H C angle in the TS increases. The tunnelings in these elimination reactions have been discussed460.

DIEs in the ion molecule reaction OH C H2CO ! H3O C CO have been

studied461. The rate constants for thermal dissociation of H3OC and D3OC in helium have been found to be 1.6 ð 10 12 cm3 s 1 and 1.1 ð 10 12 cm3 s 1 ((kH/kD D 1.455)461.

The ˛-deuterium secondary KIE kH/kD for the rearrangements of (2,2- dideuteriocyclo-propyl)chlorocarbene to chlorocyclobutenes 390 and 391 have been

17. Syntheses and uses of isotopically labelled compounds	1035
found to be equal 1.20 at 21 °C462. The corresponding theoretical	value was

calculated by ab initio methods462 and was interpreted as originating in hybridization changes at the migrating carbon atom. Deuterium has been applied463 in the study of the intramolecular reactivity of arylcarbenes, 2-(alkoxymethyl)phenylcarbenes, 2- ROCH2C6H4C(H):, eventually giving rise to benzylcyclobutenes as side product. The

reaction of Ar CHCF3		(Ar	D	O2NC6H	4	with various bases occur according to
2	464
the E1cB mechanism		(equation 229). The additions and E1cB eliminations by salts

(equation 230) have been studied465 and D KIE values of 1.28 š 0.02 and 1.87 š 0.04 have been observed for the reactions of Ar2CDF3 and Ar2CDCOOEt, respectively. Such low values of kH/kD for the reaction between C-acids and bases are observed when the TS is product-like or when D/H exchange with the solvent interferes with D KIE determinations. Supplementary test experiments suggested that the former is responsible for the low kH/kD values observed465.

C

slow

D

very fast

D

Ar2CHCF3

B

!

Ar2C

CF2

!

HF

F

k2

k1(CHX)

Ar2CHCR2X X

Ar2CDCR2 X

Ar C R2X

C

C

k

2

k

(

HX)

2

D

D

D

Cl

Cl

D

(390)

(391)

229

230

Stable isotope effect studies carried out during 1972 1992 concerning correlation of IEs with molecular forces and molecular structures, correlation of zero-point energy and its IEs with molecular forces and molecular structure, vapour pressure isotope effects and fractionation of stable isotopes have been reviewed466.

Nuclear tunnelling in the aqueous iron (2C)-iron (3C) electron transfer has been investigated467 and the rate enhancement for H2O has been assessed to be 65 times the classical rate, and that for D2O 25 times the classical rate, yielding a H/D isotope effect of 2.6. The occurrence of the general base catalysis and sizable primary D KIEs indicated that the isomerization of 1H-indene-1-carboxylic acid to 1H-indene-3-carboxylic acid in aqueous solution takes place through an enolization reketonization sequence468. Kinetic HH/HD/DD isotope and solvent effects have been used in a dynamic NMR study469 of the tautomerization of 15N-and 2H -labelled bicyclic oxalamidines.

The stereoselectivity of the gas-phase 1,2-eliminations of deuterium-labelled 392 and of 393 with several bases have been studied470. The SDIE has been used471 to study the mechanism of hydrolysis of the enol ether, 2-MeOCDCHC6H4COOH, which yields the acylal, 394, rather than the formal product of hydrolysis.

The acidic properties of (methoxymethylcarbene)pentacarbonylchromium, 395, have

been known for many years472. A rapid conversion of 395 CH3 into 395-CD3 has been observed in dilute NaOCH3/CH3OD solution473. Recently474 DKIEs [kH/kD D k1OH (395-

CH3)/k1OH (395-CD3) of the order of 2.5 3.0 for the deprotonation of 395-CD3 by OH in various MeCN water mixtures and kH/kD D k1OH (395-CH2Ph)/k1OH (395-CD2Ph) of

1036	Mieczysław Ziełinski´ and Marianna Kanska´

CMe3

MeO CMe3

OMe

O

		MeO
Me	Me	Me	Me
			O
	(392)	(393)	(394)

2.53 š 0.10 in the deprotonation of benzylmethoxycarbenepentacarbonylchromium, 395- CH2Ph, also by OH , as well as D KIE of 5.51š 0.35 in the deprotonation of 395-CH2Ph by piperidine have been measured474. The lower values of D KIE observed in this study than in the deprotonation of other C H acids have been explained by assuming that, apart from compressing the C C bond and stretching the M C (carbene) bond, the M C(CO) and C O bonds are also affected. A substantial coupling of proton transfer to heavy-atom motion involving bond changes in the CO ligands is observed (in THF, where 395-CH2 is stable). The CO stretching frequency shifts from 1941 cm 1 in 395-CH3 to 1898 cm 1 in 395-CH2 due to charge delocalization into the carbonyl ligands475,476.

OCH3			OCH3	OCH3
		−C		−
(CO)5Cr C	(CO)5Cr		CH2	(CO)5Cr C
CH3				CH2
(395) - CH3	(395) - CH −			(395) - resonance structure
		2
	OCH3			OCH3
(CO)5Cr	C	(CO)5Cr		C
	CD3			CH2 Ph
(395) - CD3			(395) - CH2 Ph

Primary D KIEs in the hydrogen abstractions at 130 °C from PhOH vs PhOD by t- butoxy radical have been found477 to equal 1.33 š 0.029 (in CCl4), 1.40 š 0.19 (C6H6), 2.79 š 0.03 (MeCN). In the analogous reaction (equation 231) with PhSH vs PhSD the kH/kD values are in the range 1.02, 1.05 and 1.07 in CCl4 C6H6 and MeCN, respectively (asymmetrical TS). In the reactions of PhCH3/PhCD3, the kH/kD IEs are 6.76 (CCl4, 4.40 (C6H6) and 5.38 (MeCN), respectively. H/D isotope effects for radical abstraction reactions are discussed by Denisov478.

kH D	231
PhXH(D) C t-BuOž ! PhXž C t-BuOH(D)

X D S or O

The solvent deuterium IEs for the acid-catalysed hydrolysis of benzaldehyde diaryl thioacetals479, PhCH(SC6H4R)2 (where R D H, R D NO2, m-Cl, p-Cl, p-OMe), are 1.46.

17. Syntheses and uses of isotopically labelled compounds

1037

Small hydrogen KIEs of kH/kD D 1.2 1.3 have been observed480 in the reaction of an equimolar mixture of adamantane and 1,3,5,7-tetradeuterio-adamantane (kH/kD D 1.30 š 0.05 1.31 š 0.05) with nitronium tetrafluoroborate, and in nitration of 1- deuterioadamantane with pure nitronium tetrafluoroborate in nitroethane solvent (kH/kD D 1.20 š 0.05) and interpreted as indicating a non-linear highly unsymmetrical TS in the RDS of the reaction 232.

			O			+
			N	O			NO2
						+
		+	+			−H
			NO2
				−				−
		+	NO2					− NO2
H	ONO		−HNO2			H	+ NO
			OH				O
			+			+NO+	−HONO	+
			H2 O
		− H+	NO2−	H	+
	NO2		ONO

(232)

		Me		Me	Me
			+
(D)H		(CH2 )nSCH2 R		(CH2 )nSCH2 R	(CH2 )n
	OPNB		(D)H	(D)H	+S
				RCH2
(396)		R = H, n = 2, 3, 6		(398)	(399)
(397)		R = Ph, n = 2, 3, 6

˛-Deuterium IE of 1.18 1.20 at 50 °C has been observed481 in the stepwise solvolysis (path k1 in equation 233) of 2-(ω-methylthioalkyl)- and (ω-benzylthioalkyl)-3-methyl- 2-cyclohexenyl p-nitrobenzoates 396 and 397 in 80 vol% ethanol, which involves an allylic cation 398 as a reaction intermediate and kH˛ /kD˛ D 1.01 1.03 in the solvolysis involving neighboring sulphur participation (k2 path in equation 234) and formation of an intermediate cyclic sulphonium cation 399. Compounds 400 and 401 are produced in the path (k1), compounds 402 and 403 in the reaction path (k2). The rate of oxidation of acetylacetone by chloramine-T and bromamine-T in the presence of hydrochloric acid

1038	Mieczysław Ziełinski´ and Marianna Kanska´

increased in D2O medium482.

[ 396 (or 397) ]			398
k1
	Me				Me
		+							(233)
	(CH2 )nSCHR1				(CH2 )nSCHR
(D)H
OR2					(D)H
(400)					(401)
R2 = H or Et					Me
									Me
k2							+
[ 396 (or 397) ]		399			(CH )		OR2		(CH2 )n
					2	n
					(D)H		(D)H	S
					SCH2 R
					(402)			(403)	(234)

In neutral medium the deuterium solvent isotope effect, (kH2O/kD2O), in the hydrolysis of diaryldiacyloxyspirosulphuranes483, 404 407 has been found to be 1.66. In acidic medium the ratio of catalytic rate constants has been found to be 0.56. Heterocondensed imidazoles 408, are produced in the reaction of N-benzylamides, 409, of nitrogen heterocyclic carboxylic acids with phosphorus pentachloride. Deuterium labelling experiments have been carried out to understand the mechanism of this reaction involving a nitrile ylide species484.

N	N	CONHCH2 Ph
	N
Ph
(408)		(409)

The reactions between OH or OD radicals and CO at temperatures down to 80 K have been studied485a.

Isotope effect studies of the mechanism of hydration of alkynes with formic acid as water donor485b,485c leading to ketones (equation 234a) have been undertaken recently485d by observing the kinetic isotope fractionation of 13C in the course of carbon monoxide