Mannich-type condensation products of sulfinic acids with aldehydes and hydroxylamines or hydroxamic acids

renti.

Vol. 16. pp. 5653 to 5664.

Papllm

Pra9 1970.

Prinmd in Great Britain

MANNICH-TYPE CONDENSATION PRODUCTS OF SULFINIC ACIDS WITH ALDEHYDES AND HYDROXYLAMINES OR HYDROXAMIC ACIDS AN ESR STUDY OF DERIVED NITROXIDES G. RAWSON and J. B. F. N. ENGBEMX Department of Organic Chemistry, The University, Zemikelaan, Groningen, The Netherlands (Received in the UK 13 Augusr 1970; Acceptedfor publication 19 August 1970) Ab&ae-Hydroxylamine and some of its derivatives, including hydroxamic acids, have been used as the amine component in Mannich-typt condensation reactions with aldehydes and sulfinic acids or thiols. The condensation products have been oxidized to the corresponding nitroxides. The ESR spectra of these nitroxides am reported and interpreted in terms of the structure of these radicals. In several cases the ESR spectra showed alternating line-widths and varied with temperature and solvent.

INTRODUCTION SULRINIC acids

can be used as the acidic component in Mannich-type condensation reactions with aldehydes and primary or secondary amines,’ (thio)carbamates,2 carboxamides,’ sulfonamides3 or lactams.3 R’ RS02H + R’CHO + HNXY -+ RS02CHNXY

+ H,O

(1)

The nature of the amine component is important in determining the possible variation in the aldehyde structure. In the cases of amines, the reaction is restricted to formaldehyde as the carbonyl component but with less nucleophilic bases a variety of aliphatic or aromatic aldehydes may be used successfully. A number of the condensation products have found application as initiators of polymerization reactions* and show other interesting chemicals and stereochemical properties. In the present investigation the scope of the reaction (1) has been extended to hydroxylamine and several derivatives, including hydroxamic acid as the amine component. The use of these nitrogen bases as the amine component in Mannich-type reactions fmds only limited precedent in the literature.’ The condensation products, which are new classes of hydroxylamines, offered the possibility of oxidation to the corresponding nitroxide radicals. Since ESR spectral data provide detailed information on the electronic structure and conformational properties of free radicals, the ESR hypertine splitting constants of these new classes of nitroxides have been measured and compared. SYNTHESIS

Hydroxylamine and several derivatives successfully underwent condensation with sulfinic acids and aldehydes. A few reactions with arenethiols, instead of arenesultlnic acids, have also been investigated. The new compounds are recorded in Table 1. 5653

5654

G. RAWSON

and J. B. F. N. ENGBEUT~

Use of ‘hydroxylamines. Hydroxylamine has been used as the acidic reactant*v9 in the Mannich-type condensation with formaldehyde and secondary amines, and as the amine component9-’ l only in the reaction with formaldehyde and some CH acidic components. We found that with an arenesulfinic acid as the active hydrogen reactant and hydroxylamine as the amine component, the condensation reactions with formaldehyde were easily performed in acidic aqueous solutions using formic acid as the catalyst. A rapid reaction occurred at room temperature and crystallization of the condensation product started immediately after mixing the reactants. In all cases the IR spectra of the products (OH stretching at 3450-3510 cm-‘; SO1 stretching at h 1140 and 1320 cm-‘) and the PMR spectra (characteristic singlet at -8 4.5 ppm for the SO&I-&N group) showed unequivocally that both H atoms at the N atom of hydroxylamine are replaced to give bis-N-(sulfonyhnethyl)hydroxylamines (la-ld).

2RS0,H

+ 2CH,O + NH,OH

+ (RSO,CHs),NOH

+ 2H,O

(2)

la-ld No reaction products could be obtained by replacing formaldehyde with other aliphatic or aromatic aldehydes. In both respects the behaviour of hydroxylamine resembles aliphatic primary amines.12~ l3 Using N-phenylhydroxylamine with ptoluenesulftic acid and formaldehyde resulted in condensation to give N-phenyl-N-(p-tolylsulfonyhnethyl)hydroxylamine(2) (yield 75%). N-Phenylhydroxylamine resembles anilineI in its ability to condense with arenesulfinic acids and formaldehyde. This may be compared with ethyl NphenylcarbamateZb which failed to react with p-toluenesulfmic acid and formaldehyde, probably being the result of the further decreased nuleophilicity of the nitrogen atom due to the electronic effect of the ester function. By replacing hydroxylamine with N-alkylhydroxylamines (e.g. cyclohexyl, isopropyl, t-butyl) no reaction products could be obtained. Use of benzohydroxumic acid. Benzohydroxamic acid is known’ to be an active hydrogen component which reacts with formaldehyde and secondary amines to give the N-aminomethylation products. However, benzohydroxamic acid can also behave as the amine component in a Mannich-type condensation which is illustrated by its reaction with arenesulfinic acids, and formaldehyde at room temperature, with formic acid as catalyst, to give the corresponding N-hydroxy-N-(sulfonylmethyl)benzamides (4a4d). RSO,H + R’CHO + C,H&ONHOH

-. RS02CHN(OH)COC6H,

+ H,O

(3)

I

R’ 4a-4d The condensation products separated as oils after about 12 hr and upon work up became solid products (Experimental). With ptoluenesulfinic acid and benzohydroxamic acid the condensation products with some higher aliphatic aldehydes (R’ = Et, iso-Pr) were isolated (4e, 30”/, ; 4f, 53%). Crystallization of the products started after about 12 hr. Due to their instability no pure reaction products could be isolated from aromatic aldehydes.

Mannich-type condensation products of sulfinic acids

5655

Benzohydroxamic acid condensed appreciably more slowly than hydroxylamine, presumably due to the less nucleophilic N atom. In this reaction the hydroxamic acid behaves similarly to the carboxamides3 in their reaction with sulfmic acids and aldehydes. The products, 4a4f, showed characteristic IR absorption bands at 16o(rl640 cm - ’ (CO str) and - 1140 and 1320 cm-’ (SO2 str) while the OH stretching frequencies (3300-3400 cm-‘) were found at a lower value as compared with la-ld. Use sf N-hydroxybenzenesulfonamide. Hellmann and Teichmann9 have reported the use of N-hydroxybenzenesulfonamide as the acidic component in a Mannich-type reaction with formaldehyde and secondary amines. We found that N-hydroxybenzenesulfonamide can also be used as the basic component as is shown by the condensation with ptoluenesulfinic acid and formaldehyde to give 6a (yield 68%) or with propionaldehyde to give 6b (yield 80”/,). The reaction could be carried out at room temperature and crystallization of the products started after several hours. Benzaldehyde failed to give the corresponding product. RSO,H + R’CHO + C,H,SO,NHOH

--* RSO,CHN(OH)SO,C,H,

+ H,O

(4)

R’ 6a-6d N-Hydroxybenzenesulfonamide also reacted smoothly with ethanesulfinic acid to give 6c (yield 46%) and I-adamantanesultinic acid to give 66 (yield 64%). This reaction can be compared3 favourably with the condensation of benzenesulfonamide with sulfinic acids and aldehydes. IR and PMR spectral data were in accordance with the proposed structures and showed characteristic absorptions due to the groups introduced into the N-hydroxybenzenesulfonamide. Use of arenthiols. An investigation Is* l6 of the reactions of arenethiols with secondary amines and formaldehyde indicates that in general, N+.rylthiomethyl)-N,Ndialkylamines are formed. With arenethiols, formaldehyde and hydroxylamine using formic acid as catalyst, at 50-70” for several hours, condensation occurs to yield bis-N-(arylthiomethyl)hydroxylamines (3a, 52%; 3b 68%). Benzohydroxamic acid reacts with p-toluenethiol and formaldehyde, at 50”, to give N-hydroxy-N-(p-tolylthiomethyl)benzamide 5 (yield 68%). Similarly N-hydroxybenzenesulfonamide also reacts with p-toluenethiol and formaldehyde, at 50”, but attempts to obtain the analytically pure product were unsuccessful. Stability and mechanism. Several of the compounds, particularly 2 and the benzohydroxamic acid derivatives (4a-42,5) are unstable and slowly decompose at room temperature. When heated in some solvents, e.g. benzene or ethanol, they decompose. Therefore crystallization was carried out at low temperature (Experimental). This type of behaviour in solution may be compared to the instability of N,N-disubstituted aminomethylsulfones which has been attributedI to the low nucleophilicity of the sulfinate ions and inductive effects of the N-substituents. The details of the mechanism of this Man&h-type reaction with hydroxylamine derivatives, aldehydes and sulfinic acids are not known but it is very likely that the first step will be a condensation reaction of the aldehyde with the hydroxylamine

G.RAWSON andJ.B.F.N.

5656

ENGBERTS

rather than with the sultinic acid. The reaction rate will depend on such factors” as PI-I, nucleophilicity of the nitrogen atom, nature of aldehyde and ease of crystallimtion of the condensation products. NITROXIDE

RADICALS DERIVED CONDENSATION

FROM THE PRODUCTS

HYDROXYLAMINE

The new hydroxylamine derivatives (Table 1) obtained by the Mannich-type reaction described in the preceding section were all converted into the corresponding nitroxide radicals by oxidation with PbO, in CH,Cl,. ESR hyperfme splitting (hfs) constants and g-values are given in Table 2 The structural assignment of the nitroxides is based on the following evidence: (i) the hypetfme splitting patterns are those expected for the proposed structures (uide in&r); (ii) a series of hydroxylamines gives, upon oxidation, the expected related ESR spectra and (iii) the preparation of 7b by using an independent route, i.e. peracid oxidation’* of bis+-tolylsulfonylmethyl)amine.

(jKH3CsHoS02CH2)2NHpNo’C6H’Co’H~

(JKH&H,SO~CH,)~NO

(5)

The relation between the electronic structure of the nitroxide function and the observed ESR spectral data has been the subject of a number of investigations.1g Generally the unpaired electron delocalization may be described in terms of two resonance structures A and B. It has been shown ” that the nitrogen hfs constant is dependent on the configuration around the N atom, deviation from planarity of the N-O moiety resulting in a larger ONvalue. For nitroxides which have a planar

Y'

I

A

y’ B

or apprOXiIIUtelyphmr COdigUratiOI'I aN VahCS were shown” t0 COrrehte With the spin density at the N atom and are dependent on the inductive and resonance effects of the substituents X and Y. Changes of the spin distribution in the NO group will also be accompanied by variations of the g-values. Since spin-orbit coupling is somewhat larger for oxygen than for nitrogen, an increase of the uN value will result in a decrease of the g-value. The results given in Table 2 clearly demonstrate significant effects of the various substituents at the NO group on the ESR spectra of the nitroxides. The bis-(arylsulfonylmethyl)nitroxides 7a-76 show smaller ah’ values (109 gauss) than usually found for dialkylnitroxides (15-16 gauss).22 This can be attributed to the electron withdrawing effect of the two ArSO,CH, groups (polar substituent constant cr* - 1.3)23 which will favour resonance structure A relative to B. The four magnetically equivalent g-H atoms of 7a-7d form a 1:4:6:4:1 quintet with un, about 6 gauss (see Fig 1). All the nitroxides described in this paper which possess a CH, or CH group attached to the nitroxide function exhibit +, values smaller than those expected (on the basis of the McConnell equation24) for free rotation about the N-CH2 or N-
Man&h-type

5657

condensation products of sulftic acids

formations around the N---CHz or N--CH bond has been previously observed” for a number of nitroxides. In nitroxide )3,the unpaired electron is delocalized into the phenyl ring Due to the inductive effect of the arenesulfonyl group the cN value is 1.1 gauss smaller than that found for ethyl phenylnitroxide. M Replacement of the arenesulfonyl groups in

10 gJurr

FIG 1. ESR spectrum of bis~tolylsulfonylmethyl)nitroxide

(7b).

7a-7d by aKmthi0 groups (!hdb) results in larger nitrogen hfs constants ((IN= 13.5 gauss) in accordance with the decrease in electron withdrawing ability of the substituents. The ESR spectra of the benzoylnitroxides lOa-101 and 11 are characterised by small nitrogen hfs constants ((INh 7G-7.25 gauss)* indicating a lower spin density on the N atom than is found for 7a-7d and 9a-9b. This is supported by a concommitent increase in the g-values compared with 7a-7d or !Ia-9h @ = 2GO66-6!3 and 29061 resp). The reduced nitrogen hfs constants can be best reconciled with electron pair delocalization such as C CLD which will be favoured over unpaired electron delocalization.2* p

1p1

RSO,CH.N---CC,H,

+ -. RS0,CH2N,Hd e

1p1

C

lyl”

D

l These 6 valua may be compared with those of bcnz.oyl bmylnitroxidc bcnzoyl I-phenylethylnitroxid (o,, = 76 gauss).”

(a,,, = 75 gauss~’

and

5658

G. RAWON

and J. B. F. N. ENGBDW

This explains why in lOa-1Of the S-sulfonyhnethyl moiety is not particularly effective in further lowering the a, values since the inductive effect of the RSO&H, group will destabilize resonance structure D. As is also found for the nitroxides 7a-74 very little change in spin density on the N atom is observed as a function of the p-substituent in the arenesulfonyl group of ma-1Od. The very small S-hydrogen hfs constants for 1Oe (aHg= 1.25 gauss, Fig 2) and lof (cub = O-3 gauss) indicates that in the favoured conformation the &H atom is situated close to the nodal plane of the nitrogen p-orbital.2g These conformational effects may be readily seen from molecular models.

FIG 2. ESR spectrum of benzoyl (1-ptolylsulfonylpropyl)nitroxide

(1Oe).

The aryl- and alkylsulfonylmethyl benzenesulfonylnitroxides (12a-12d) show appreciably larger nitrogen hfs constants (aN h 10.1-104 gauss) than the corresponding benzoylmtroxides (compare 12a and lob; 1% and Me). This is in accordance with a recent study of alkyl and aryl benzenesulfonylnitroxides (13) and bis-@enxenesulfonyl)nitroxide (14) by De Boer et al. 3” The relatively high nitrogen hfs constants (&I * 10-12 gauss) found by them are explained by assuming that the unpaired electron occupies an orbital with increased s-character as compared with acyl- and alkylnitroxides. Our results support this theory. The almost equal a, values of 7a and 14 are completely unexpected in view of the sensitivity of the nitrogen hfs constants to electrostatic effects of substituents at the NO function but can be reasonably accounted for in terms of a more pyramidal structure of the nitroxide group in 14 and hence an increase in orbital s-character. Line-width altemution. Since all nitroxides 7-U show hindered rotation around the N-CH, bond, as indicated by the low aHp values, an alternating line-width effect3’ might be observed Indeed, at room temperature significant line-width alternation is apparent in the triplet from the S-H atoms of lOa-lOd, 12a, 12c and 12d, due to slow exchange (on the ESR time scale) between two favoured conformations having magnetically nonequivalent B-H atoms. The ESR spectra of 1Oa and

Mannich-type condensation products of sulfmic acids

5659

:;;;‘I& &l/pp~ i II

FIG 3. ESR spectra of benmyl (phenylsulfonylmethyl)nitroxide (c) -8l”and(d) -110”.

,‘..

(1Om)at (a) +25”, (b) -21”.

RG 4. ESR spectra of phcnylsulfonyl @-tolylsulfonylmethyl)nitroxidc. (12a) at (a) +25”, (b) -34 and (c) - 58”.

Yield m.p.V (%)

102-104 49.24 106-107 5201 95-96 47.86 108-l 10 3897 79-82 60.63 45-46 6291 72-73 3864 148-149 57.72 141-141.5 5901 143143.5 5667 148-148.5 5060 1105-l 11.5 61.24 1345-135 62.22 94-95 65.92 158-1585 49.25 91.7-92.7 5201 155-155.5 39.84 162-162.5 5297

49G-l 51.91 47.71 3917 60.21 62.95 38.37 57.70 5924 55.23 49.82 61.19 61QO 6589 4908 5206 3891 52.96

..------~~~~-~-----_-..

4.43 5.19 4.77 305 5.45 6.27 3ffl 4.50 496 4.71 3.60 5.74 609 5-53 4.43 5.19 4.83 6Ql

4.41 5.23 4,91 3.21 546 636 2.89 4.59 5.24 475 3.84 5.67 6.10 55’7 441 5.18 4.84 6.08

4.11 3.80 349 9.74 5.05 459 3.22 4.81 4.59 4.36 8.33 4.20 403 5.13 4.10 3.80 5.16 3.63

392 392 3.36 9.63 498 462 3-23 4.81 456 4.00 8.38 405 397 5-02 393 3.63 499 3.60 9.24 978 9.25 11.61 18.74 1748 2296 1660

9.53 9.62 9.22 11.73 18.78 17.35 23.63 16.63

5.38 5.335*78(m) 5.35-565(m) S-12 4.53 4.8&-5.16(m) 4.38 4.39

3400,1620,1330,1150 3400,1640,13 10,1138’ 3300,1635,1315,1140 3200.1600 3370,1350,1320,1168,1140 3310,1365.1308,1170. 1130 3505,1365,1325,1170.1135’ 3400,1355,1310,1175,1135

359 3W 3310,1630,1320,1150 3340,1635,1330,1145’ 3320,1635.1320,1145

2094 15.01 1095 10.56 9.42

21Qo 14.14 llcL0 1050 998

447 451 525 5-20 5.16

34M, 1350,114o 3450,1310,1140

1488 1492 406 11.56 11.57 4.87

.,____________ 3520,1320,1145’ 3510,132Q 1145’ 3510,1345,1147’

.-_-_----------_________..

IR absorption bands (cm’)

18.78 18.81 4-63 17.36 17.45 4.55 1590 15.85 445

* Decomposition points. b Unstable, difftculties with purifications. ’ PMR spectra recorded in acetone-d,; 4f in DMSOd,. ‘ IR spectra recorded in CH,Cls (30 m&ml) othetwise in Nujol Mulls.

42 38 56 64 15 52 68 28 26 21 42 30 53 68 50 80 46 64

.

&SO&&NC C H N S -------------.----------.. -.----------------. -- &LIN talc. found talc. found talc. found talc. found (Ppm)

..---_______-____---_-~~~_-------------~.

la (C,H,SO&H,),NOH lb (p-CH,C,H,SO,CH,),NOH IC @CH,OCsH,SOICHs),NOH Id @NO,C,H,SO$Hx),NOH 2 C,H,@CHsC,H,SO,CH,)NOH 3s @-CH&,H,SCHs),NOH 3h ~B~~H.SCH~)~NOH 4a C,H,S0,CH2N(OH)COC,H, 4h p-CH,C,H,SO,CHsN(OH)COCBHs 4e pCH,0C6H,S0&HsN(OH)OC~Hsb 4d pN0,C6H,S0,CH,N(OH)COCsHs le pCH,C,H,S0,CH(C,H,)N(OH)COC6H, 4f pCH,C,H,S0&H[CH(CH,)2]N(OH)COC,Hsb 5 ~H~C~H,SCH~N(OH~OC~H~ fin pCH,C,H,SOICH,N(OH)SO&,H, 6b pCH,C,H,SO,CH(CIHs)N(OH)SO&H, 6c C,H,SOICHIN(OH)SO,C,H, 6d I-Adamantyl S0,CHIN(OH)S02C6H,

_ -..

Hydroxylamine

_____________

No.

TABLE1

F

PJ .? ?

i *

z

Mauuich-type condensation products of sulftic acids

5661

lh have been recorded in CH,Cl, at lowered temperature and are shown in Figs 3 and 4. From the spectra observed in the slow exchange region, the two g-hydrogen h.f.c’s could be obtained (10s - llO”, aHp, = 25, uHp, = 60 gauss; 12a, - 58”, = 8.5 gauss). Since the two forms will he equally populated the ~~a~o~$“Z+ (au + aHe,) should hold, a condition which is reasonably fulfilled. Very rec&tly, Jo&man and Kommandeui2 have presented evidence that the conformational energy barrier may be a property of the solvent rather than of the molecule in those cases where a large “free volume” is associated with the conformational change. Although more extensive studies are required, including the determination of activation parameters, some of our observations may be accounted for by this theory of solvent induced conformational kinetics. Firstly, in the case of 12a the line-width alternation effect becomes stronger upon increasing viscosity of the solvent (CS, < CH,Cl, < mesitylene). Secondly, the observation of line-width alternation for lob and the absence of this effect for 11(bothat 20”) is in accordance with the larger “free volume” for conformational change for lob as compared with 11.

TABLE~.ESR SPIXIALDATA~ OF N~TROXIDERALNCALSOBTA~NEDFROMHYDRO Nitroxide

aN

78 7h 7c 7d

(C,H,SO,CH,),N-1 0 @-CH,C,H,SO,CH,),N-‘0 (pCH,OC,H,SO,CH,),N-0 (pNO,C,H,SO,CH,),N-‘0 0

8 !h 9b

pCH,C,H,SO,CH,NC,H, (pCH,C,H,SCH,),N-10 @-BrC,H,SCH,),N-.-O 0

lh

I-

I.

C,H,SO&H,NCOC,H,

XYLAMINE DERIVATWFS

other coupling constants % ..-- -_______ ---- - _---- -. ..---.----------

109 109 109 LO.9

59 5.8 60 5.9

10.0 135 13.5

5.38 (2H) 79 (4H) 7.0 (4H)

2.0061

(4H) (4H) (4H) (4H)

7.0

45 (2H)

7.0

45 (2H)

I. 1OC p-CH,OC,H,SO,CHsNCOC,H, 0

79

4,5 (2H)

I. lO$, pNO,C,H,SO,CHsNCOC,H, 0

70

4.5 (2H)

7.1

1.25 (1H)

7.1

0.3 (1H)

g-value -_---

a_-a

= 2.92; a__” = 0.81 2Go66

2-0066

0 lob

I. p-CH,C,H,S02CH,NCOC,H, 0

1

1Oe pCH,C,H,SO,CHNCOC,H,

aa = 0.25 (2H)

I C,H, 0

I.

1Of pCHjCgH$02CHNCOCsH,

I WCW,

b

2.0069

5662

G. hWSON

and J. B. F. N. E~oag~rs

TABLE 2-continued

Nitroxide

aN

11

pCH 3C 6H l SCH 1LCOC 6H I

7.25

12a

pCH,C,H,SOICH,NSO,C,H, 0

IO.1

other

coupling constants

g-value

4.25 (2H-)

6Q (2H)

1.

12b pCH,C,H,SO,CHNSO,C,H,

10.25

I W-b 0

1.

Ik

CIH,SOICH,NSO,C,H,

10.4

6.2 (2H)

IO.4

60 (2H)

0 124

1.

I-Adamantyl SO,CHINSO,C,H, 0

13 14

C H SO k-Alkyl’ (&&d,),N~ -01

11-12 10.5, IO’

” All ESR spectra were obtained in CH,Cl, at 25”. H.f.c’s are given in gauss. b a”_ was not resolved. ’ H.k of only one d the two magnetically different -f-hydrogen atoms could be resolved. ASee Rd 30.

EXPERIMENTAL The m.p (to be considered as decomposition points) were determined on a Mettkr FP2 apparatus with microscope attachment. Microanalyses were carried out in the Analytical Section of the Department under the direction of Mr. W. hi. Hazenberg PMR spectra were taken on a V,arian A-60 spectrometer using TMS (6 = 0) as an internal standard IR spectra were determined by the normal Nujoll Mull or solution techniques on a Unicam SP200 or Perkin-Elmer Model 125 Grating Infrared Spectrophotometer. The ESR spectra were measured on a Varian E3 apparatus g-Values were determined using solid l,ldipbenyl-2-picrylhydrazyl (B = 2-036) as an external standard with an accuracy of k(Hw102 The nitroxides were prepared in siti by PbO, oxidation, at room temp. of diluted (4 mg/ml) solns of the hydroxylamina in CH&l,. All the nitroxidcs (except 12~ and 12d) were stabk in solution for at least.2 hr. whik the benxoylnitroxides (lOa-lof) showed unfaded ESR spectra for more than 5 hr. Commercial sodium benzenesullinate and sodium ptoluenesulfinate were used. The sodium sulfinates RSO,Na with R = pCH,0C6H,,‘3 p-NO&H,,” 1-adamantane,3’ Et36; N-phenylhydroxylamin,” benzohydroxamic acidJo and N-hydroxybenzenesulfonamide39 were prepared by standard procedures. The condensation products were recrystallized by dissolution in methykne chloride at 25” and subsequent cooling of the soln to -20’. Most of the condensation products tended to decompose slowly at room temp and were stored at -20”. No attempts were made to optimise yields. Bis-N-(arylsulfonylmethyl)hydroxylamines (la-d)

Hydroxylamine hydrochloride (@35 g, 005 mole) was added to a soln of the appropriate sodium arenesulfinate (001 mole) in 10 ml water under an atmosphere of N,. Afta the addition d 36”/, aqueous formaldehyde soln (0011 mole) the soln was acidified with 4 ml formic acid. Precipitation of the product occurred immediately. After stirring for a further 30 mins the solid was filtered ON,washed successively with water and n-hexane, dried and then recrystallized from methylenc chloride at -20”.

Mannicb-type condensation products of sultinic acids N-Phmyl-N~ptolylsuny~thyl)hydroxylm

5663

(2)

N-Pbenylbydroxylamine (1.1 g Oal mole) was added to a rapidly stirred sob of 1.8 g (001 mole) sodium p-toluenesulfmate in 20 ml water under an atmosphere of N,. After the addition of 36% aqueous formaldehyde sobr (0011 mole) the sobr was acidified with 5 ml formk acid. An oily produd was formed after several min which solidified over a period of about 45 min. Work up of tbe yellowish solid, as described above for la-d, gave 21 g (75%) of the desired product. Bis-N-(arylthiomethyl)hydroxybnines

(34 b)

A mixture of the appropriate arenetbiol(OO1 mole), hydroxylamine hydrochloride (0.35 g O-005mole), 36% aqueous formaldehyde sobr (0+X1 mole) and 3 ml formic acid in 20 ml water, was prepared as descrihed above for la-d, and heated at 70” for 2 hr. The mixture was then cooled to room temp and the solid products worked up as described above for lad. N-Hydroxy-N-(alkyl-

OTaryl-sulfonylmethyl)benzamides (4a-f)

Potassium benxobydroxamic acid (1.5 g 001 mole) was added to a stirred sobr of the appropriate sodium sullinate (001 mole) in 10 ml water under an atmosphere of N,. After the addition of 36% aqueous formaldehyde soln (O-011 mole) and 4 ml formic acid the mixture was set aside at room temp for 15 hr. An oily product was obtained wbicb on trituration with n-hexane resulted in the formation of a white solid which was worked up in tbe usual way. With compounds 4e and 4f, in which propionaldebyde (041 mole) and iso-butyraldehyde (001 mole) were used respectively, tbe required products crystallixed from the solution after about 12 hr. N-Hydroxy-N-(p-tolylthiomethyl)benzamide (5) A mixture of ptoluenetbiol (1.24 g 001 mole), potassium benzohydroxamic

acid (1.5 g 001 mole), 36% aqueous formaldehyde soln (Oal mole) and 5 ml formic acid in 15 ml water was heated at 55” for 1 hr under an atmosphere of N,; then set aside at room temp for 24 hr. The oily product was extracted with methylene chloride (2 x 15 ml), the combined extracts washed with water, dried over Na,SO,, and the solvent evaporated in uactw. ‘The remaining oil was dissolved in tbe minimum amount of methylene chloride and cooled in a Dry-Ice-acetone bath Upon the addition of n-hexane to this cold sobr a white solid precipitated; this was filtered off and recrystallixal from methylene chloride at low temp to give 16g(68%)ofS. N-Hydroxy-N-(gtolylsulfonylmethyl)ben.zenesulfonamide

(61)

N-Hydroxybenunesulfonamide (1.73 g 001 mole), sodium p-toluenesultinate (1.8 g. 001 mole), 36% aqueous formaldehyde soln (011 mole), 5 ml formic acid and 10 ml water were mixed under N, and the soln set aside at room temp. The first crystals were observed after several br and crystallization was complete after 12 his Work up as above gave 1.7 g (50”/.) of tbe desired product. With propionaldebyde (OCllmole) the produd 6b crystallized from the solution after 30 min (yield WA). N-Hydroxy-N-(ethylsulfonylmethyl)benzenesuljbnamide

(6~)

From sodium etbanesulfmate (001 mole) as described above for 6r An oil was produced after several days which was triturated with n-bexane to give a white solid; this was filtered off and recrystallixed from methylene chloride to give 1.3 g (46%) of 6c. N-Hydroxy-N~l-adamantylsulfonylmethyl)ben.zenewlfonam&

(6d)

To a suspension do.225 g (0011 mole) of 1-adamantanesulfinic acid in 15 ml of water was added 19 ml of 5.8 N NaOHaq to convert tbe acid into its soluble Na salt. N-Hydroxybenxenesulfonamide (@19 g, OC011 mole), 36% aqueous formaldehyde soln (00011 mole) and 3 ml formic acid were added to the soln which was set aside at room temp. Crystallization started after about 4 br and after 16 hr the yield d 6d amounted to @28 g (69%). Acknowledgement-One

of us (GR) isindebted to the Netherlands Organization for Pure Research (Z.W.O.) for the award of a Fellowship. Tbe authors wish to express their thanks to Prof. J. Kommandeur d the Physical Chemistry Department, d these Laboratories, for putting the ESR-equipment at their disposal, and to Prof. J. Strating for bis encouragement.

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and J. B. F. N. ENQBBR~ REFERENCES

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