DECEMBER

1957

MONOCARBAMATES OF

1,%DIHYDROXY-3-ARYLOXYPROPANES

1595

[CON"RIBUTIONFROM THE NEW YORK QUININEAND CHEMICAL WORKS, INC.]

Monocarbarnates of 1,2-Dihydroxy-3-aryloxypropanes
MANUEL M. BAIZER, JOHN R. CLARK,

AND

JOHN SWIDINSKY'

Received April IS, 1967
Ester interchange between diethyl carbonate and 1,2-dihydroxy-3-aryloxypropanes produces high yields of dioxolones
which on treatment under mild conditions with ammonia in an alcohol give good yields of the carbamate of the primary
alcohol group. In one case (Compound If) the isomeric carbamate (of the secondary alcohol group) was isolated from mother
liquors and also synthesized by an unequivocal independent synthesis.
The rearrangement of derivatives of a-hydroxycarbamates is discussed. A method is provided for converting secondary
carbamates to primary carbamates.

Monocarbamates of 1,2-dihydroxy-3-aryloxypro- tively,6 ICwas treated with phosgene under more
panes have recently emerged as a therapeutically severe conditions than above to yield the cyclic caruseful group of ~ o m p o u n d s . ~The
- ~ presently most bonate (or dioxolone) 11,which, upon reaction
important members of this group have been formuR
lated as Ia although no rigorous proof was presented that they are indeed Ia rather than their
structural isomers Ib.
0,
&cH2cH-7H2

9

E0

R = alkyl or alkoxyl
I I a R = methoxyl

I1

OA

OB

I

with liquid ammonia, yielded the same monocarbamate as was obtained via the chlorocarbonate route.
a
H
We have found that the dioxolones I1 are obb
-CONHZ
H
tained
in very high yield by ester interchange bec
H
H
tween ICand diethyl carbonate in the presence of a
d
H
-COCl
H
--CONH2
catalytic amount of a metallic alkoxide.' The al-CONH2
H
koxide may be added from an external source or
This investigation was undertaken in order to may be formed in situ, e.g., by dissolving sodium
provide a satisfactory practical method for prepar- in molten IC.Upon completion of the ester intering the carbamates Ia and to determine by inde- change, the alkoxide is destroyed by the addipendent unequivocal synthesis whether the previ- tion of ammonium chloride and the excess diethyl
carbonate is recovered by distillation. The residous structural assignments have been correct.
Our results, reported here, are a new synthesis of ual crude cyclic carbonate is suspended in a
Ia that is suitable for manufacturing purposes and a suitable solvent (such as ethyl or isopropyl a h - .
confirmation of the structure disclosed for the mono- hol), ammonia gas is introduced, the system is
carbamate of 1,2-dihydroxy-3-(o-methoxyphenoxy) closed and the mixture is stirred at room tempropane
I n addition we have discovered a perature for 8-16 hours. After the first several
hitherto unnoted rearrangement of carbamates l e hours, the initial precipitate disappears and thereafter the somewhat turbid solution begins to deposit
and If.
crystals
copiously. Excess ammonia is expelled by
Synthesis. Monocarbamates of 1,2-dihydroxy-3aryloxypropanes (IC) have been prepared2p4 by heating, and from the cooled clarified solution8
treating a solution of ICwith one mole of phosgene, the crude product (SO-SO% yield) is recovered by
which was assumed6to react preferentially with the filtration. Recrystallization from alcohols or ethyl
primary alcohol group to yield the hydrcxychloro- acetate yields 60-65% of pure Ia.
.carbonates (Id) (not isolated); the latter were then
(6) B. J. Ludwig and E. C. Piech, J. Am. Chem. Soc., 73,
converted by aqueous ammonia to Ia. Alterna- 5894 (1951).
A

;

B
-CONH2

R
alkyl or alkoxyl
alkyl or alkoxyl
alkyl or alkoxyl
alkyl or alkoxyl
methoxyl
methoxyl

(1) We wish to thank Dr. W. G. Bywater, S. B. Penick
and Co., for reviewing this paper.
(2) H. L. Yale, E. J. Pribyl, W. Braker, F. H. Bergeim,
and W. A. Lott, J. Am. Chem. Soc., 72,3710 (1950).
(3) New and Nonofficial Remedies," J. B. Lippincott
Co., 1956, p. 467.
( 4 ) R. S. Murphey (to A. H. Robins Co., Inc.), U. S.
Patent 2,770,649, Nov. 13, 1956.
(5) Reference (2), footnote 8.

(7)'Other catalysts such as anhydrous potassium carbonate (cf. M. s. Morgan and L. H . Cretcher, J. Am. Chem.
Soc., 68, 783 (1946)) are also effective.
(8) An aliquot of the solution was taken to dryness
in vacuo. The weight of the residue indicated quantitative
conversion t o monocarbamates. A sample of the residue was
analyzed by Dr. Eric Smith, S. B. Penick and Co., using
infrared spectroscopy and was found to contain 70-7377, of
Ie. All other infrared data reported here were likewise
obtained by Dr. Smith.

$h-&HzCl VIII o + NaOCHaCeH5 - 0 'I guaiacol OH- OCHz i I OCONH~ V was prepared by either of two routes: ( a ) by condensation of epichlorohydrin with sodium benzylate followed by reaction of the resultant epoxide with guaiacol in the presence of a small amount of base. Chemistry and Industry. yields VIII. Further.75.. 1557i (1955). 22 gave the benzyloxycarbamate VI. (17) M. S. Chem.254 (1931). T. Swindlehurst. Daubert and C. The lower melting isomer is therefore t.. M. (e) J. ( f ) P. CLARK. A d . However.. 1621 (1920). K. D. Soc. (c) B.Soc. on treatment with phosgene followed by ammonia. 4. 5483 (1953). Chabrier.he primary carbamate Ie as previously formulated. but its formation was not suppressed by conducting the ammonolysis at higher or lower temperatures or under pres~ure. Phosgenation of V followed by reaction of the unisolated intermediate chlorocarbonate with ammonia (9) Experiments by D. chim. identical in melting point and infrared spectrum with If. Inoue. melting in the range 93-97'.1596 BAIZER. 'France. I n order to confirm this structure. J . Chem. Abstr. J .. F. Aylward and P. (b) H.1706 (1957).. E.3-dihydrorcypropane give the same di-p-nitrobenzoyl derivative.. 324 (1953). Marle. Haber.22. Hibbert and N. l 1 The tzcid-catalyzed rearrangement is considered to be an equilibrationllevfproceeding via a cyclic acetal intermediate. J. Structural Investigation.~ The infrared spectrum of If differs substantially from that of Ie in the "fingerprint region.. Chem. G. SOC. Giudicelli. G. Bull. Since a rearrangement must have occurred during the reaction of Ie with thionyl chloride. J. .60. (12) H. The rearrangement of @-glyceryl esters to a-glyceryl esters has been fairly extensively studied. Ckm." In particular If has a very strong absorption band at 10. 1601 (1929) and earlier literature cited therein.3-bis-p-nitrobenzoylZchloropropane. 25. The identity of V from either source was verified by comparison of the refractive indices of the alcohols and the melting points and mixture melting points of the p-nitrobenzoates. with nitrous acidI4 to yield Marle's chlorohydrin IV. J. Am. 2973 (1931). Carter.. m.6. E.. PTOC. J. (15) I n a somewhat analogous situation which illustrates the migratory possibility of the chlorine atom. Soc. Jr.4265 (1930) had found that both l-chloro-2. Clark and E. J. Rearrangements.71 (1930). chem. (13) Identity verified by infrared spectra. Greig. preferably from ethyl acetate. (10) E. Najer. i142 (1954). 316 (1912). Proc. the related rearrangements of propyl carbamates containing substituents on the carbon atom adjacent to the one bearing the carbamate function have not previously been reported. VOL.3-dihy&oxypropane and Zchloro-l. 16*17 (11) (a) E.. Hibbert and M. namely 1. B.. (14) It is taken for granted that in the nitrous acid reaction there is no disturbance of the bonds between C-1 and C-2 and their respective substituents so that further rearrangement during this deamination-decarboxylation is impossible. E. Ber. Wood. Fischer. 49.. Wetemchap.1724 (1934). .p. Am. the rea. Chem. Smith.l0 (b) by condensation of Marie's chlorohydrin IVlO with sodium benzylate. Am. Hydrogenolysis in isopropyl alcohol at room temperature and atmospheric pressure led to VII. Akad. Swuki and Imp. From the mother liquors remaining after the removal of pure Ie. soc. B. OCONM.. Regenbogen. and K. P. We found that the treatment of either l e OT If with thionyl chloride in pyridine led to m e and the same ~hlorocarbamate~~ for which we are suggesting the structure VI11 on the basis of the fact that it reacts OCH3 dO". Route (b) gave the better yield of V. IV. Van Lohuizen. Chem. C h . M. R. Chem. shown below to have the structure If. J. 51. The highermelting isomer was always obtained in minor yield.'5 the validity of a degradative method for establishing the structure of a-hydroxycarbamates whose first step involves replacement of -OH by -C1is open to serious question. Ser. 53. (d) B. identified by its refractive index and by the melting point of its phenylurethane. (g) F. F. SOC. Stimmel and C. Am. Verkade and 0. there was obtained by careful fractional crystallization. a quantity of isomeric carbamate. Martin. AND SWIDINSKY The results of the ammonolysis of IIa were studied in detail. Absk. 117-119". and R.17 p which is completely absent in the spectrum of Ie. Med. The preparation by independent synthesis12 of certain analogous acetals has tended to support the mechanism proposed. 24. . Abstr. 56. Research.. King. King.3003 (1938). (16) H. R. 53 (1956).ction of one mole of phosgene with IC was assumed to take place at the primary alcohol group and to lead from the chlorocarbonate to the primary monocnrbamate. Can. 56. (Tokyo). the qynthesis of If pictured in Chart I was carried out. Koninkl. Baizer. As mentioned above. Org.

no useful product could be obtained from the mother liquor.At h t a dense almost unstirrable precipitate formed which dissolved and then reprecipitated.C a r b a m m y . however.is present. at least in part. The total of Ie was 406. attack occurs at least in part at C-2.. 5. The still warm (50') crude molten IIa was mixed with 100 ml.0 mole) of molten (100') 1.1 mole) of sodium methylate and 472 g. (4 mole) of ammonia in 2400 ml. ane To 396.5-96. Neither If nor Ie reacted at room temperature with two moles of hydrogen chloride in isopropyl alcohol.0 mole) of diethyl carbonate.4 g. isopropyl alcohol and added with stirring to a solution of 68 g. but at 50-60" they were converted to the dioxolone in 33% and 40% yield respectively.A kilogram of partly solvenbfree (400g. Isolation of l .6 g. (28. EXPERIMENTAL^^ + The acyclic carbonium ions IX-X which may be written to represent formally the initial products of reaction form a common cyclic transition cation.When the internal temperature was 130°. When allowed to stand overnight at room temperature in chloroform saturated with hydrogen chloride. The virtual identity of the yield of Ie in a given period from either 11s or from If (or from Ie second crops).0O. IIa. and 6 g. 95-96. for CuHuOr: C. (19.7%) was obtained by rearranging 15. After the rearrangement and removal of the pure Ie formed. solid) mother liquor from several Ie preparations was recrystallized from 2 litera of ethyl acetate. and the equilibration of Ie under similar conditions to a mixture from which 60435% of Te can be recovered strongly suggest that the rearrangement described here occurs via ring closure of the carbamates to IIa followed by ring-opening to give Ie and If in an approxima.30. sodium hydroxide. the melting point waa lowered (94-112') but upon recrystallization of the crude product only If could be recovered. was successful.04. ' * Calcd.p. The remainder of the ethanol and excess diethyl carbonate were then distilled in vaew (25mm. sodium isopropoxide.6%). indicating further decomposition of the dioxolone. m. m.DECEMBER 1957 MONOCARBAhIATEs OF ~.4%) of Ie. and the ethanol which formed distilled at 79-84".4 g. of ammonium chloride was added. when OH. Another 8. On cooling. phosgene. treated with charcoal. I.~ ~ r ~ ~ y ~ ( ~ ~ x y p h propane (I. (22) Microanalyses by Schwsrzkopf Microanalytical Laboratory.H. The residue was dissolved in 2400 ml.4-69.) on a steam bath. No depression was observed in a mixture melting point with Ie prepared by Murphey's' procedure from 1. A second crop. but in this case ammonia eacaped and. and filtered.tely 7 :3 ratio.5%) more of Ie. m. When the environment contains C1-. attack appears to proceed predominantly a t C-1.p. In an effort to increase the overall yield of Ie from IIa attempts were made to rearrange If to Ie.0'. Y. under the same conditions Ie yielded about 45% of the dioxolone and 42% of unchanged starting material.p. (21) Melting points are corrected.%DIHYDROXY-~-ARYTJOXYPROPANEB A second shift occurs. 304 g. heating was stopped. Woodside. piperidine waa inoperative.\ OCH~CHCH~OCONH~ OSOCl OCHa I VI11 + AgOH - +OH percent of catalyst in the presence of an ammonia atmosphere yielded about 6 M 5 % of pure Sodium ethoxide. + Ie s o c i 2-+ 6 . (3. 117-119") was heated under reflux in toluene containing a catalytic amount of p-toluenesulfonic acid. 58.) to an internal temperature of 130'.40. 90-105"was obtained. m. the observed liberation of ammonia during the rearrangement conducted in the absence of added gas.92. l9Obviously the carbamtes were stable to small amounts of acid and in the presence of larger quantities lost ammonia and underwent recyclization. The rearrangement of If with the aid of strong alkaline catalysts capable of supplying alkoxide or hydroxide ions. Found: C.2dihydroxy-3(o-methoxyphenoxy)propane was added with stirring 5.4 g. of hot ethyl acetate.p. This substance was rearranged (see separate section on rearrangement) to yield 94 g. The mixture was heated with stirring.). 5. the aggregate of whose resonance forms can be represented by XI. crude dioxolone. 94. 94.4%). N. of the alcohol.0'. (19) There was continuous evolution of carbon dioxide.p. (2. 68. and benzyltrimethyl ammonium hydroxide were effective catalysts. The mixture was stirred overnight at room temperature in a tightly stoppered flask.4 g. (84. boiling points are not. When If (m. (0. m. The 2-propanol and ammonia were removed in vaew (120 mm. although the yield of Ie was normal.2%) of a third crop obtained from the mother liquors of the rearranged second crop.~ h y d r o x y ~ ( ~ y p h e n o x y ) p r o p(Ie).596. (4. The mother liquor was (20) The rearrangement also occurred when the mixture was heated under reflux for 24 hours. (63. A small amount of the residue was recrystallized from ethyl acetate. when VI11 is treated with freshly prepared silver oxide in 50% isopropyl alcohol: a small yield of Ie was then the only definite product isolated from this reaction. the second crop material could again be rearranged to Ie in the same yield as above.h y d r ~ . (1. The residue. 142 g. . A d .18 These rearrangements may be rationalized as indicated.p. Stirring a suspension of If in isopropyl or ethyl alcohol overnight at room temperature with about two mole (18) The reaction is complicated by the possibility that simultaneous dehydrohalogenation occurs. 1597 l . and ammonia.Zdihydroxy&(o-methoxyphenoxy)propane.59.5' was obtained. If was converted almost completely to its dioxolone. was w d without purification for the next step. L. H.

4 g. of dry toluene. the residue dissolved in 50 ml. To 12. and a solution of 15 g. Similar results were obtained with isopropyl alcohol as a solvent. H. b.5-5 LI 125-145"' (bath temperature).8 g. The aqueous was extracted with toluene. 90-105". of 50% aqueous acetic acid to give 56. no depression in mixed melting point $5 ith prwiously obtained mnteriai. 72-81 '. (76%) of crude If. Upon rhillinp. AnaE. 10 ml. N.15 g. a t 0-10' and for 1 hr. only a few crystals m. I-Benzyloxy-2-hydroxy-S-(o-methoxyphenoxy)-propane (V) ( a ) T o 2.he bases.02 mole) of Ie and 50 ml. m. A sample was redistilled for analysis. Evaporation of the mother liquor and recrystallization of the rclsidue from 2-propanol yielded 2.024 mole) of sodium in 1200 ml. b.5-76. (0. 2.7 g. H. of anhydrous 3 A alcohol. The residue was dissolved in 700 ml. dried (sodium sulfate) and distilled (Hickmani still) to give 6.) on a steam bath.0'. (0. 7.03 g. R = CHa) was again used without further purification. 120-130°/0. A solution of 1.0%) of Mephenesin carbamate.7 mm. theory for sodium chloride. 82-84'. 5.0 g. of impure If.33. 104-116" crystallized. m. Found: C.o &rid overnight a t room temperature.5 g.p.0' was obtained. H.70 g. m. the reaction mixture (cold) was extracted with IN sodium hydroxide to remove excess guaiacol The toluene solution gave upon distillation in high vacuum (Hiclrman still) 1.4 g.p.0025 g.04 mole) of concentrated aqueous ammonia for 2 hr.01 mole) of 111 in 10 ml. 5&64'. (1 mole) of ammonia in 200 ml. (0.05 g. 94 5-96.. 1. The hot toluene solution was charcoaled and chilled to yield 101 g. No depression in mixture melting point with . charcoaled. eharcoaled.p.76 g. H.82 g. Anal. 70.012 mole) of phosgene in 15 nil. (44%) of Ha. of a saturated hydrogen chloride solution in chloroform was allowed t. more. After 3 kr.8%) of VI. Upon cooling. 76-81"/0.2 g. n y 1. 88.01 mole) of V and 1.Z-dihydroxy-3-(o-methylphenoxy)propane ( MepheneEiin).of hot ethyl acetate. (40%) of Ie. Jf gave mostly IIa. and the toluene removed. of ice water added. at 0-5'. m.81.22.6%) of Ie. of dry toluene was added with stirring a t (t-5" in 1 hr.p. of 2-propanol wan stirred overnight at room temperature In a tightly stoppered flask.52 mole) of epichlorohydrin was added after cooling to room temperature. 54.12. The mixture was stirred for 2. A solution of 0. and chilled to give 7. H. m. no depression in mixed melting point with previously obtained material. m. of toluene. no depression in mixed melting point with l e previously obtained. Found: C.p. Anal. of anhydrous 3 A alcohol.7%) of crude Mephenesin carbamates. (0.p. Calcd.. The mixture was cooled. m. of a hydrate. (0. was added 1.5-96.2 9. Ammonium chloride (0. The residue was triturated with hexane to give 3. water and dilute hydrochloric acid were added to neutrality. 65. 1.1 was added. The toluene solution was washed with water.23 Found: C . for C18H2105N: C./0. at 25'.4 g.5576-1.1 g.6 ml. To a aolution of 1.67 g. (0.20. (71.5" was obtained. 108--112" were also ibolated.08. A thick suspension resulted to which 49.27.5594.4 g . VOL.09. After rrmovd of chloroform and hydrogen chloride..044 mole) of hydrogen chloride in 32 ml.20. of toluene. 1. (17. 1200 ml.08 g. l-Hydroxy-~-carbamoxy-3-(o-nLethoxyphenoxy)propane (If ).25. and reflux was continued for 1. H.56 g.77. m. 6.5577. CLARK.1%) of Ie. 6. The mixture was stirred overnight a t room temperature in a tightly stoppered flask. m. Upon two recrystallizations from diisopropyl ether./l i~ 120' (bath temperature). for CI1Hl6O6N:C.81. Found: C. 6. of fine sodium shot in 300 ml. of dry benzyl alcohol was added 6. H.0005 mm. and the 2-propanol and ammonia removed in vacuum (120 mm.p.7 g. and the salts filtered (1. (0.9%) of 111.4-96. I-Benzyloxy-Gcarbamoxy-S-( o-methoxyphenoxy )propane (VI). dried (sodium sulfate). 5. and chilled to give 94 g. Anal. 114-116" which upon treatment with 1. of dry toluene a t 45' was added with stirring a solution of 17 g.8 g.014 mole) of dimethylaniline in 10 ml.31. (48.37.24 Rearrangement of If to l e .59 mole) of second crop obtained in the initial l e preparation described above. 94. 3. Ammonium chloride (0.5 hr. (0. (33. of a third crop m.5%) was removed by filtration of the hot solution. m. and chilled to give 113 g. and stirred with 2. A sample of the dioxolone recrystallized from methanol melted a t 95. 4. atom) of sodium in 25> mi.0'. b. N.7 g. of sodium methylate. for ClaH~07N:C.8%) of V.03 mole) of l-chloro-2-hydroxy-3-(o-methoxyphenoxy) propane (IV). of crystals m.5 hr. n y 1.4%) IIa. 116-118' which gave 85 g. (0. of 15% Pd/C a t room temperature and atmospheric pressure. l-Carbamoxy-%hydroxy-3-(o-methylphenoxy)propane (Mephenesin carbamate). bp. 7.5 mole) of l. (after (23) Reported6 96-97".%?-propanol. for CloHlzOe:C. For separation of 1-carbamoxy-shydroxy-3-(o-methylphenoxy)propane. m. The mixture was heated to 80' a t which point a vigorous reaction started. 1.25.30.p.5572. 117-119' upon recrystallization from ethyl acetate. Rmction of l e and If with hydrogen chloride. of ether added. (0. (theory 19.29 g.).p.p.52 g. 21. N.) was added. m. of 2-propanol and 4. The mixture was stirred overnight a t room temperature. H.75 g. of a saturated solution of ammonia in ethanol was added a solution of 0. 6. (0.05 mole) of If and 80 ml. of reflux. of ice water. (0.18 g.39. (0. N. (0.p. After drying (sodium sulfate) the toluene solution and distilling 14. From the mother liquor by concentration was obtained 15. AND SWvlD1NskY concentrated u. n g 1. of sodium was dissolved. After 7 hr. Upon recrystallization from benzene with initial removal of water by azeotropic distillation.. the preparation of sodium benzylate was completed by refluxing until no more sodium remained.48 g.4 g.16 g. 73. (0.88 g. the crude product wa8 recrystallized from 505 ml. N. of cold (5") 2% hydrochloric acid.5148-1.89. 118 g. 94-96'. The crude dioxolone (11.27.5 g. 117-119" upon recrystallization from ethyl acetate. (40%) of IIa in a similar readion. n y 1.99. The mixture was filtered and concentrated to a small volume.92 g..7 ml. 65. of 2-propanol gave 8. 100.06 g.8 g . (0.64 g. (89. (24) Reported0 93-94". 5. 54. 22 recrystallization from 2-propanol) 68-7Um. 10 ml. 72.5150 was obtained. m. m. 7. 5.82 g. (bath temperature).p.p.p.5%) of V.0 g.02 mole) of guaiacol in 10 ml. and the toluene layer separated. After stirring overnight a t room temperature.2-Epoxy-bbenzyloxypropane (111). and with sodium hydroxide. (66.19 g. m. 1. 6. 65. ( b ) In .-atom) of sodium in 20 ml. ET. The solid soon dissolved to form a cloitdy solution.3-0.02 mole) of l e was heated overnight at 55-60". 72. It was washed with 10 ml. 92-44'.p. for C17H~0O~: C. 92-93. of dry toluene was added 50. No rearrangement occurred with piperidine or Dowex I-X (hydroxide cycle).8 9. 0.8 g.98. ( a ) In chloroform. 66-67'. m. I n analogous manner 91 g. The reaction subsided in 5-10 min. If gave 1.i598 kAIkER.24.23 To the crude dioxolone suspended in 300 ml. (54.056 g. the ethanol was removed. ( b ) A mixture of 142 g. ( 1 mole) of diethyl carbonate were allowed to react. N. ml.5 g. (0.. (0.96.6%) of Ie.10 This substance was somewhat impure. of ammonia and 0. 7. in which 0. no depression in mixed melting point. Found: G. of sodium dissolved in 120 ml.p. of 2propanol was hydrogenated over 0. 73-75'. Anal.p.88 millimole) of VI in 18 ml. (0. the residue was recrystnllized from benzene to give 2. Calcd.5 mole) of benzyl alcohol.14. 65. ( b ) To a solution of 0. The alcohol and ammonia were removed by distillation. H.lal The mixture was heated to 110-120° for 24 hr. 3. (36. and the toluene layer removed. 54. (0. 73. Calcd. Calcd. Ammonium chloride (0.27.p.p 74. The products from both reactions gave the same p-nitrobenzoate with p-nitrobenzoyl chloride and pyridine.p. Calcd.91 g. A mixture of 4.p.0°. of hot 2-propanol. (63.) of hydrogen was absorbed.88 mole) of ammonia arid 0. 4.06. (52. The ether solution was washed' with water. and benzyltrimethylammonium hydroxide as t.p. cooled. ( a ) To a mixture of 12.

Massachusetts Instit. The benzene was removed. After 4 hr. [CoNTRIBUTION FROM I599 MALLINCKRODT CHEMICAL LABORATORY AT HARVARD UNIVERSITY] Cycloalkyl. We now wish to report the preparation of a number of cyclopentyl-.10 g.p. (0.6%). Lesbre. of toluene was added below 20".. Manulkin. Luitjen and G. Found: C1. at G 5 " . 6. After filtration and washing with water and benzene. ice cold 5% hydrochloric acid.-CdHd (n-CaH9)&K&H9-sec. the phenyl group is cleaved in preference to the cyclohexyl group by the action of concentrated hydrochloric acid on (cyclo-CaHll)2Sn(CsH. a t room temperature. Gen. and n-Bu2SnMe2 is described.6 g (0.) was added to the cooled (25") reaction mixture.5' after recrystallization (2-propanol). M..p. m. All gave the same infrared absorption spectra.d with stirring at 80°C in 30 min.39.41 g. To a stirring solution 20 g. 1955. Greenford. (5) F.p. A mixture of 5. remove1 of solvent.5 g. The mixture was then slowly heated to reflux until the evolution of sulfur dioxide stopped (constant internal temperature) and for 30 min. N. 13.and Secondary Alkyltin Compounds and Their Cleavage by Iodine in Benzene Solution DIETMAR SEYFERT" Received June 16. m. (16.6 g./l p 90-100' (bath temperature). 118.014 mole) of dry pyridine was added 1. (3) T.p. (0. (32. a t room temperature and several minutes on the steam bath. S. of 50% 2-propanol was refluxed for 4 hr. All three preparations showed no depressions in mixed melting points.).7%) of IV. It has been established that (1) Present address: Department of Chemistry. and benzene recrystallization. 105.S. (0. n-Bu).SnMez.02 mole) of VI11 and freshly precipitated silver hydroxide (from 3. of dry toluene a t 20" was added 9. 4 g. ( c ) From ZV.5".50 mole) of Ie.10 mole) of phosgene in 100 ml. of acetic acid was ad2li.01 mole) of If in 1.50 mole) of dry pyridine.5 g.)z. 105-106" was obtained.5106. but. n'. (2) E. except in the case of those compounds which contained phenyl groups. J . (iso-Pr)2Snill (R = Me. Reaction of VZIZ with nitrous acid.-Bu). to 170 ml. organotin compounds containing secondary alkyl groups have been the subject of only a small number of s t ~ d i e s .5 g. Ber. 240.1967 The preparation of (cyclo-Cd30)2SnR* and (cyclo-CJ&&SnRz ( R = Me. m. However. van der Kerk.26 1-Chloro-2-carbamoxy-S-( o-meth0xyphenoxy)propane (VTII). 1.5' was obtained with phenyl isocyanate. Krause and R. (0. (U.58. Upon recrystallization from 1propanol. 0. 111. (0. Meynier.10 mole) of dimethylaniline in 75 ml.2 g. Compt. NEWARK.026 mole) of VI11 in 50 ml. 1047 (1944). A. (0. 1850 (1938). A. To a solution of B.0923 mole) of IV in 135 ml. 104-106" C.~ Little is known of the position of cycloalkyl and secondary alkyl groups in the cleavage series for organotin compounds. Gen. The crude product was filtered and recrystallized from 2-propanol to give 1.9 g. for CllHllO&lN: C1.p. Mass.67 g. To a mixture of 120. 9496°C was obtained. These compounds were cleaved by the action of one equivalent of iodine in refluxing benzene solution to give mixtures of both possible cleavage products.1 g.S. After 1 hr. of dry benzene was added with stirring at 0-10" in I hr. D. (0. water was added to the cooled reaction mixture.55 mole) of thionyl chloride. 57.5%) of VIII. and A. Znvestigations in the Field of Organotin Chemistry. m. of silver nitrate) in 60 ml. p.). J. Pohland. was filtered and recrystallized twice from 2-propanol. It was stated by Luitjen and van der Kerk (ref. 8 . Water (200 ml. 5. Calcd. Blaizot. The toluene solution was washed with ice water. Kocheshkov. Chem. 1732 (1955). M.(sec.S. No drpression in mixed melting point with Ie previously prepared was observed.5-120. M. 14. 0.4 g. Twelve new organotin iodides of formula R2R'SnI are described. cyclohexyl-. of concentrated aqueous ammonia.0125 mole) of thionyl chloride..S. 12. (0.p.s thus showing that the latter group behaves like an aliphatic group. no experiments have been reported which determine the place of a cycloalkyl group in the aliphatic organotin cleavage series. J. (0. Ana2. of water. p.p. After filtration.AND SECONDARY ALKYLTIN COMPOUNDS If isolated from I e reaction mixtures was observed. appears to provide experimental proof for this generalization. The mixture was poured into 250 ml. and extracted with benzene. the THE product. J .4 g. (30. 542 (1924). (64.ute of Technology. Tin Research Institute. m. I n the latter compounds only phenyl cleavage was observed.5". England. of dry toluene. (4) Z.4 g.R. (0. of sodium nitrite in 10 ml.DECEMBER 1957 CYCLOALKYL. 65.p. and 500 ml. 105-106. of Ie m. (87. 104-104. 78-88' was obtained. The infrared absorption spectra of both were identical. b.N. of waier. ( b ) From If. ( a ) From l e .7 g. After 1 hr. Two liquid phases which crystallized rapidly formed.p. G.8 g. of crystals m. To an ice cooled solution of 2. A phenyl urethane m. CBHs). m.R. and added. (U. more. (25) A Perkin-Elmer Model 21 was used.5430. (6) J. 80) that secondary alkyl groups arc cleaved from a tin atom prior to n-alkyl groups.65. 5. N. 105.54. a t 0-5". rend. no mixed melting point depression with the urethane froin IV obtained by Mar1e's:C method.6%) of VIII. 13.5-119. 5 g. The mother liquor was distilled (Hickman still) to give 1.5".0 g. ice water. Reaction of VZZZ with silver hydroxide. Chem. Cambridge 39. ~ ." 3.p. a quantitative product study of only one reaction4 + IZ +(n-CJL)3Sn1 + sec. and the residue recrystallized from fresh benzene to give 2.02 mole. 2*s Similarly. Only two publications have thus far been concerned with cycloalkyltin compounds. Bobashinskaya and K. and secondary alkyltin compounds and the results of the cleavage of . 119. Caujolle.4%) of unchanged VIII. n-Bu. 47.