Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups / 0261 307

6. Dipole moments of compounds containing double bonds				271
	CH3		CH3
	N		N −
X	C	X	C
	N(CH3 )2		+
			N(CH3 )2
R = H	m exp 2.48
	(23a)		(23b)

configuration E is unacceptable since the direction of mm would have no physical meaning, while for the configuration Z, mm has approximately the expected direction from N toward N0 . Nevertheless, the configuration was confirmed independently from the NOE in 1H NMR spectra95. The value of mm 0.88 D means weaker conjugation than say in amides or thioamides and is also rather dependent on the substitution on the two N atoms, i.e. on their basicity. The problem of evaluating the extent of conjugation is generally complex. One has to keep in mind that one always compares an experimental dipole moment of a real molecule with an anticipated moment of an idealized nonrealistic structure (Figure 1). Further details of the analysis will be explained later (Section V.D) on the example of amides concerning which several approaches89,96 99 can be compared.

Configuration of N,N-disubstituted amidines is thus regularly E, reversed rather than in amidines with a free NH2 group which are Z95. Derivatives with only one substituent at the amino group are in the middle and their conformation may be sensitive to small steric effects. In 24 a tautomeric equilibrium would be degenerate, hence the problem is simplified. In the case of N,N0-diaryl derivatives, three forms are possible (24a c); the fourth would be very improbable for steric reasons. From dipole moments an equilibrium

X

E

Me	−	N

C −

N

N−Me

H

	=	N
C

m

Me

−

N

mm

Z

exp

N

	CH3
	N	CH3
(NO2)	C
	N	CH3
	CH3

FIGURE 1. Determination of the configuration (E or Z) and of the electron distribution (the mesomeric dipole moment m) of the amidine 23 on the basis of the experimental dipole moment ( exp)

272	Otto Exner

of 24a and 24b was deduced100 while the mesomeric moment was found to be near to zero. The configuration and conformation of N,N0-dimethyl-4-nitrobenzamidine observed in the crystalline form101 corresponds to 24b (in contrast to the very similar amidoxime derivative; see later, Section IV.C). Dipole moments have not yet been published102 but are also in agreement with an equilibrium of two forms, corresponding to 24a and 24b.

Ar		Ar
N		N	N	Ar
H C	H	C	H C
N	H	N Ar	N	H
Ar		H	Ar
(24a)		(24b)	(24c)
Ar = C6H5	m exp 1.83

C. Conjugated Systems C=N−X

To this class belong first the derivatives of hydroxylamine, i.e. oximes and related compounds; much less attention has been given to the derivatives of hydrazine. The stereochemistry of oximes is connected with dipole moments by a long tradition since the configuration of nitrones was the first historical success of this approach103, in fact the first solution of a stereochemical problem by a purely physical method. The history was described in the previous report2. However, the tradition is misleading and oximes are not just a suitable object for determining configurations by dipole moments. The problem is not so much in the a priori unknown conformation on the N O bond, since this is almost uniformely ap as in 25. More important is the n conjugation within the system CDN O. Although it is evidently not strong, it may depreciate the results since the difference between stereoisomers is also small: it is dependent only on the small bond moment N O, whose value was redetermined and essentially confirmed104. Determination of configuration of oximes105,106 and of similar derivatives107 109 was thus in the past depreciated by the unknown extent of conjugation, which was usually included in any way into the values of the bond moments, with a better or worse approximation. Today, when the configuration of oximes is known without any doubt, the problem may be reversed and the conjugation evaluated on some derivatives with known stereochemistry.

As a model system, benzophenone oxime and its two stereoisomeric 4-bromo derivatives (25) were chosen110. The direction of the experimental group moment was determined by triangulation, and the mesomeric moment estimated to be 1.62 D in the expected direction, approximately from O toward C. In the O-methyl derivatives (26) the mesomeric moment is reduced to 0.75 D. These results were confirmed by a statistical analysis of bond lengths in the CDN O system110. They prove an evident conjugation and thus explain certain shortcomings in the previous stereochemical studies105 109 where this conjugation was neglected. New problems arose with O-acetyl oximes110. Their configuration and conformation (27) is known from dipole moments and from X-ray but mm has a strange direction from C toward O in the CDNO group. Evidently the interpretation by mesomeric formulas is not sufficient for all kinds of electron distribution. It is true that results of such analysis may be affected by the conjugation with the benzene ring which can be only approximately corrected for. Nevertheless, MW spectroscopy of the simple (E)-acetaldoxime111 yielded a similar value and direction of the dipole moment (in the gas phase); analysis into components was not attempted.

6. Dipole moments of compounds containing double bonds		273
X	X
O H	O+ H
C N	C − N

Y	Y
X,Y = H m exp 1.08
(25a)	(25b)
X	X
		CH3
O CH3		O C
C N	C N	O

Y	Y
m exp 0.66	m exp 3.75
(26)	(27)

A unique system with strong conjugation is represented by nitrones (imine oxides) (28) since already the basic mesomeric formula 28a is polar. Configuration on the CDN bond is well known; in the past it has been determined first by dipole moments103. A recent dipole study98 was thus concentrated on the electron distribution as expressed by the mesomeric formulas 28a c. When 28a is taken as basic reference structure, a participation of 28b should by manifested by a mesomeric moment oriented from O toward C, in the case of 28c from C to N. The mm found was almost exactly from O toward N and was interpreted tentatively by a structure in which the nitrogen atom allocates somewhat more than its equivalent of eight electrons. This somewhat strange hypothesis is confirmed by the bond lengths: while N O is markedly shortened, CDN is not stretched. The same effect was observed with azoxy compounds5 (weaker) and was considered also with nitro compounds112 (stronger).

In the past, an important problem was distinguishing nitrones from the isomeric oxime O-ethers113. Among other possibilities the difference in dipole moments2 is also quite

274		Otto Exner
H	CH3	H	CH3	H	CH3
C	N+	C −	N+	C	+
					N
	O−		O		O−

X	X	X
(28a)	(28b)	(28c)
X = H mexp	3.49

convincing; compare for instance 26 and 28. In the case of stereoisomeric benzaldoxime- O-trityl ethers (29) the experimental dipole moments were used only for a proof114 that 29b does not possess the nitrone structure 30 as believed previously. Configuration of 29 was determined mostly by chemical reasoning, although it would follow also from the dipole moment rather safely: within the framework of conventional bond moments 29b should have somewhat greater than 29a.

H	OC(C6 H5)3	H		H	C(C6 H5)3
C	N	C	N	C	N +
C6 H5		C6 H5	OC(C6 H5)3	C6 H5	O−
	mexp 0.84		mexp 1.23	mcalc	3.4
	(29a)		(29b)	(30)

D. Conjugated Systems X−C=N−Y

Mesomeric moments within the group CDN O can also explain the long controversy concerning the configuration of hydroximoyl chlorides. Both E and Z configurations (31) were claimed on the basis of dipole moment values108,109; the analyses were only slightly different but the final results were controversial. The problem is that the configuration on CDN itself has only small impact on the dipole moment: more consequential are the conformation on the N O bond and the mesomeric moments. The latter was not taken into account at that time, so that a misassignment could easily arise. Shortly after these publications, the configuration (31a) was solved by X-ray analysis115, after overcoming purely technical problems. With a knowledge of configuration in the crystal state, it was easy to prove that it is unchanged in solution116 (opposite cases are very rare in the field of CDN configurations117); then the dipole moments were analyzed again116. Compared to standard bond moments, there is a change of electron density which, however, cannot be expressed by any simple mesomeric structure. Formally, it can be visualized as if the polarity of the C Cl bond would be reduced. The misassignment was also made possible by the choice of improper model compounds. Note that even a cyclic reference model compound was investigated109 whose dipole moment did not agree with standard bond moments116: nevertheless the assignment109 made on its basis was right. This shows that the correct and incorrect assignments in this case were essentially fortuitous.

	6. Dipole moments of compounds containing double bonds				275
			R
Cl	O R	Cl	O	Cl	Cl
C	N	C	N	C N	C N
				O R	O
					R
X		X	X	X
(31a)		(31b)		(31c)	(31d)

The importance of a suitable model is clearly seen from the example of O- benzoylbezhydroximoyl chlorides (32) which were investigated independently at the same time118. Although the molecule of 32 is evidently more complex than 31, its configuration and conformation (32a) can be determined more easily and more reliably. Very important is the possibility of introducing substituents from two sides. It enables a solution to be achieved even without resorting to the bond moments within the CDN O grouping, by simple triangulation based only on the Car Cl bond moments. In the first approximation one can say that of the parent compound is not much changed by substitution with chlorine on either end (32a). Further proofs, also quite convincing, were obtained by comparison of UV, NMR and IR spectra with substituted (E)-O-benzoylbenzaldoximes118, whose steric arrangement is well known.

				X
				Cl
Cl		O	C	C N	O
	C	N	O	O	C
				X
X					X
X = H	m exp 2.09
X = Cl	m exp 1.79
		(32a)		(32b)

O-Methylbenzhydroximoyl chlorides (31, R D CH3) were prepared later. A great advantage was that both stereoisomers were isolated. The first assignment of configuration on the basis of dipole moment119 was wrong for the same reason as in the case of parent hydroximoyl chlorides. A definite solution was again achieved by X-ray analysis120. With the knowledge of configuration and conformation and with the experience acquired above, an analysis of dipole moments was undertaken121 focused only on the conjugation or electron distribution. A relatively small mesomeric moment mm was revealed, oriented approximately from O toward C in both stereoisomers. In terms of mesomeric structures,

276	Otto Exner

it should be represented by an electron transfer from O up to the benzene ring in 31a. In the isomer 31c the vector mm suggests an electron transfer toward chlorine which cannot be easily represented by a mesomeric structure. Very similar results were obtained with hydroximoyl cyanides 33, which were also isolated in both stereoisomers122. The main result is that conjugation is evidently dependent on configuration: it is stronger when the conjugated groups are in trans position. With a knowledge of mesomeric corrections it was possible to determine configuration of (Z)-O-benzoylbenzhydroximoyl cyanide (34) which was obtained only as one stereoisomer122, while a 4,40-bis-derivative was not available.

X

NC	O R	NC	NC	O	C
C	N	C N	C	N	O
		O	R
X		X	X
(33a)		(33b)		(34)

The derivatives of O-methylacethydroximic acid (35) and S-methylthiobenzhydroximic acid (36) contain still one additional axis of rotation, the C OMe or C SMe bond, respectively. Their steric arrangement could be determined from dipole moments123,124 when previous experience on similar compounds was exploited. In 35 the conformation on N O was assumed ap as it is uniformly in all derivatives of this type; also the conformation sp on C O in the ester group is beyond discussion. Conformation of the methoxy group was in similar derivatives rather flexible107; it can be approximated by a free rotation or by equal representation of the two planar conformations. With these assumptions it was not difficult to decide123 between E and Z configurations on the CDN bond: the observed configuration Z is common for benzoyl derivatives of oximes and of hydroximic acids. In the second case (36) there was an advantage of having both stereoisomers124. With similar assumptions as above (free rotation around the C S bond etc.), the calculated dipole

			NO2
			CH3		CH3
	CH3		S	O CH3	S
			C	N	C N
	O	O
			C		O CH3
	C	N	O

H3 C

(35)

(36a)

(36b)

6. Dipole moments of compounds containing double bonds

277

moments were sufficiently different for the two stereoisomers. The result was supported by systematic comparison of several derivatives, some of which could be assigned by special methods, for instance exploiting intramolecular hydrogen bonds124.

Various substituted amidoximes have been investigated from both the point of view of steric arrangement and conjugation. The problem is that both stereoisomers were isolated only rarely125; moreover, the configuration is not uniform and depends on the substitution on nitrogen. Amidoximes with an unsubstituted NH2 group are known only in one isomer. Isolation of the second, less stable stereoisomers was assumed as impossible since a prototropic equilibration would be possible126. Steric arrangement in solution was investigated by means of dipole moments in the standard approach126. Of the four a priori possible forms 37a d, the Z configuration was revealed unambiguously, together with the conformation ap on the N O bond (37a) which is common for all oximino derivatives. The same steric arrangement follows from the dipole moments of O-benzoyl derivatives (38), where it is determined with yet more certainty due to the possibility of introducing substituents from either side. (In the first approximation the configuration is evident from the dichloro derivative 38.) Configuration and conformation of these simple amidoximes is thus uniform, both in solution and in the crystalline state. In the subsequent dipole moment study of additional substituted amidoximes attention was focused on the conformation in the rest of the molecule127.

			H
H2 N	O H	H2 N	O	H2 N
C	N	C	N	C N

O H

X	X	X
(37a)	(37b)	(37c)
		Y

H2 N	H2 N	O	C
C N	C	N	O
	O
H
X	X

X = Y = H m exp 4.71

X = Y = Cl m exp 4.58

(37d)

(38)

278	Otto Exner

In N,N-dialkylamidoximes a reversal of configuration takes place. The stable form is E,ap (39c), which was found several times in crystal and is also compatible with the dipole moments in solution128. It seems thus common for all amidoximes with two substituents in the amino group. When two stereoisomers are isolated125, then the form corresponding to 39c is thermodynamically stable. Also, O-benzoyl derivatives 40 keep the same arrangement128: in this case exp of the dichloro derivative is distinctly different.

(CH3 )2 N

O H

C N

X

(39a)

(CH3 )2 N

C N

O

H

X

(39d)

H
(CH3 )2 N	O (CH3 )2 N
C N	C N

O H

X	X
(39b)	(39c)
(CH3 )2 N
C N	O
O	C

X

Y

X = Y = H mexp 4.38

X = Y = Cl mexp 3.57

(40)

It remains to mention derivatives with just one substituent on the NH2 group. Concerning the configuration, they should take an intermediate position: in addition, one has to deal with the conformation on C N. These compounds have been less studied. Compared to structurally very similar amidines, a remarkable difference was found101. While N,N0-dimethyl-4-nitrobenzamidine in the crystal is in the form E,sp (41), N0-methyl- 4-nitrobenzamidoxime is Z,ap (42). Dipole moments in solution are compatible with a conformational equilibrium, but analysis is made imprecise by the mesomeric moments which are not known exactly102. In a previous analysis129 of of derivatives similar to 42 (H and Cl in place of NO2) the form Z,ap was also preferred, although the presence of a minor conformer could not be completely excluded.

Nitrone derivatives of a unique structure were prepared recently130. The two stereoisomers 43a and 43b are in equilibrium in solution; configuration was determined by means of NMR spectroscopy. Dipole moments were calculated by MNDO for both stereoisomers, but were not measured. In our opinion one suitable approach has thus been omitted.

In the chemistry of hydrazones, some specific problems may arise. Dipole moments of ˛-chlorohydrazones 44 suggested the configuration Z and conformation ac on the N N

6. Dipole moments of compounds containing double bonds						279
	CH3			H
H	N		CH3	N	O	H
	C N			C	N
	CH3
NO2			NO2
	(41)			(42)
CH3 O	C(CH3 )3		CH3	O	O−
C	N+			C	N+
	O−				C(CH3 )3
mcalc	3.31			mcalc 4.71
(43a)				(43b)

Y

	Cl
X	C		H	C	O	N
						N
	N	N		O		CH3
						N
				C	N	CH3

X

(44)

(45)

bond131, in agreement with the crystal structure, but the fit with experiment was rather bad. A formal explanation was suggested that the N N bond, connecting two quite different atoms, should be attributed a small bond moment directed from Nsp3 toward Nsp2 . This is evidently an ad hoc explanation and should be verified on further examples.

280	Otto Exner
Another example	from the chemistry of hydrazones (45) represents a complex

problem132. The group moment of the heterocycle was taken from theoretical calculations; conformation on (O)C O is evident. One has to determine conformations on N N and (N)C O bonds, but the most important problem is the configuration. The final result was a form near to 45 with a torsional angle <C O C C near to 90°. In previous examples, we preferred to express the conformations at this position as an equilibrium of two planar forms or a formally ‘free rotation’: all these interpretations are indistinguishable within the framework of dipole moment theory. In any case, this example is at the limits of possibilities of this approach.

V. C=O BONDS

A. Isolated C=O Bonds

An isolated CDO cannot give rise to any configuration. Within the framework of the bond moment scheme, all aliphatic oxo compounds should possess equal dipole moments. The CDO bond moment could be derived from of formaldehyde, measured with extreme accuracy33 (2.33168 D). Within the second approximation, individual carbonyl compounds can be distinguished133 since the CDO dipole is large and produces perceptible induced moments in the hydrocarbon rest. For the same reason the mutual position of several carbonyl groups has a great impact on the molecular moment, and the conformation can be investigated relatively easily134. Usually this conformation is not very interesting: when the functional groups are separated by a longer chain, it is then approaching the statistical model of a free rotation of all parts (random coil)2. Also, in halogen ketones, the mutual position of CDO and C Hal dipoles has a great impact on the overall dipole moments and their electrostatic interaction is considered an important factor controlling the conformational equilibrium8,13. In steroidal ketones with an additional substituent, the values of were used to determine conformation of the six-membered ring10.

The dipole moment of a carbonyl compound can also be strongly influenced by an intramolecular hydrogen bond. In hydroxyketones 46 the dipole moments anticipated from bond moments (mBM) were compared with experiment135 and the difference expressed as a vector mH expressing the electron transfer due to hydrogen bonding (equation 2). Surprisingly, the direction of mH was not from carbonyl oxygen toward hydrogen but merely in the direction of the O H bond.

		mH D mexp mBM			2
	O			O	H +
X	C	H	X	C
	CH2	O		CH2	O−
	mH 1.36
	(46)			(46a)

This result was explained by simple AM1 calculations136 which suggested that the most important electron transfer takes place in the carbonyl group, from carbon toward oxygen. In the whole conception one must imagine a pseudomolecule which has the exact geometry of the real, hydrogen-bonded molecule but does not contain any hydrogen bond. Such a pseudomolecule must also be modeled in the quantum chemical calculations.