US3621038A

US3621038A - Derivatives of 2-azido-2-hydroxy-1-naphthaleneacetic acid{65 -lactones and preparation thereof

Info

Publication number: US3621038A
Application number: US855408A
Authority: US
Inventors: George Santroch; Martin A Davis
Original assignee: Ayerst Mckenna and Harrison Inc
Current assignee: Wyeth Canada Inc
Priority date: 1969-09-04
Filing date: 1969-09-04
Publication date: 1971-11-16
Anticipated expiration: 1988-11-16

Abstract

There disclosed herein 2-azido-1-carboxy-1,2,3,4-tetrahydro-2hydroxy-7-methoxy-1-naphthaleneacetic acid gamma -lactone methyl ester and 2-azido-1,2,3,4-tetrahydro-2-hydroxy-7-methoxy1-methyl-1-naphthaleneacetic acid, gamma -lactone. The compounds have antibacterial, antifungal, and trichomonicidal activities, and methods for their preparation and use are also disclosed.

Description

0 United States Patent n113,621,038

[72] Inventors GeorgeSantmch; [50] FleldofSearch .LT. 260/3433 Martin A. Davis, both of Montreal, bee CM Que [56] Relerences Cited [2!] Appl. No. 855,408 UNITED STATES PATENTS 1 Filed p 4, 1969 2,344,595 7/1958 Waisbrot 260/3433 [45] Patented Nov. 16, 1971 I r Assignee d Primary Examiner-Nicholas S. RIZZO & hum, W cm Assistant Examiner-Anne Marie T. Tig'iie Anomeys-Vito Victor Bellino, Andrew Kafko, Joseph N Martin Weigman and Dwight J. Potter [54] DERIVATIVES 0F Z-AZIDO-Z-HYDROXY-l- I :CMLACTONES AND ABSTRACT: There disclosed herein 2-azido-l-carboxy- 5 Cum N D" l,2,3,4-tetrahydro-2-hydroxy-7-methoxy-l-naphthaleneacetic 0 acid 'y-lactone methyl ester and 2-azido-l ,2,3,4-tetrahydro-2- [52] US. 260/3433, hydroxy-7-methoxy-l-methyl-l-naphthaleneacetic acid, 7-

260/349, 260/473 F, 260/590, 260/613 D, lactone. The compounds have antibacterial, antifungal, and 424/279 trichomonicidal activities, and methods for their preparation [51] Int. L C071! 32 and use are also disclosed.

DERIVATIVES OF Z-AZIDO-Z-HYDROXY- 1- NAPHTHALENEACETIC ACIDy-LACIONES AND PREPARATION THEREOF BACKGROUND OF THE INVENTION This invention relates to derivatives of 2-azido-2-hydroxyl naphthaleneacetic acid -y-lactones, in particular to 2-azidol,2,3,4-tetrahydro-2-hydroxy-l-naphthaleneacetic acid -y-lactones of the formula I B RWOO N3 I.

in which R represents a lower alkyl group containing from one to four carbon atoms and, R represents a lower alkyl group containing from one to four carbon atoms or the group COOR in which R represents a lower alkyl group containing from one to four carbon atoms.

The compounds of this invention possess antibacterial, antifungal and trichomonicidal activities and are valuable as topically applicable disinfectants and as trichomonocidal agents. For example when subjecting the compounds of this invention to a test procedure similar to that described by Grove and Randall in Assay Methods of Antibiotics, Medical Encyclopedia Inc., New York 1955 they have been found to inhibit the growth of Staphylococcus pyogenes, both penicillinresistant and penicillin-sensitive strains, Sarcina lutea, Streptococcus fecaltlr, Escherichia coli, Aerobacter aerogenes, Salmonella pullorum, Pseudomonas aeruginosa, Proteus mirabilis, and Proteus vulgaris, as well as of Trichomonas foetus and Trichomonas vaginalis.

Similarly, when testing the compounds of this invention for their antifungal activity by a method similar to that described in Antiseptics, Disinfectants, Fungicides, and Chemical and Physical Sterilization," Lea & Febiger, Philadelphia 1957, they have been found to inhibit the growth of Candida albicans, Microsporum gypseum, and Trichophyton granulosum.

As topically applicable antibacterial and antifungal agents, the compounds of this invention may be formulated in the form of jellies, creams, lotions or ointments with pharmaceutically acceptable carriers, for example, with can-ies such as described in Remingtons Practice of Pharmacy," 12th Edition, pp. 356 and 405 (1961). Such formulations may contain from 0.1 to 1.0 percent of the active ingredient and may be applied topically to infected areas from one to several times a day. As trichomonocidal agents the compounds of this invention may be formulated in the form of jellies or creams such as described above, or in the form of vaginal tablets or inserts with pharmaceutically acceptable solid carriers, such tablets or inserts containing from 50 to 250 mg. of the active ingredient each and preferably to be applied once a day for periods of time of from 3 to 15 days.

SUMMARY OF THE INVENTION The compounds of this invention may be advantageously prepared from the commercially available 2,7-dihydroxypnaphthalene (ll), alkylating the latter compound to obtain the corresponding 2,7-dialkoxy derivative (Ill), and reducing said last-named compounds to obtain the corresponding 7-alkoxy- 2-tetralone (IV).

When it is desired to obtain the compounds of this invention in which R represents the group COOR in which R is as defined above, said last-named compound of fonnula IV is reacted with a di-(lower alkyl) carbonate, preferably dimethyl carbonate, to yield the corresponding l,2,3,4-tetrahydro-7-alkoxy-2-oxo-l-naphthalenecarboxylic acid lower alkyl ester (V). Treatment of said last-named compound with a lower alkyl haloacetic acid ester of the formula XCl-LCOOR in which X represents a halogen with an atomic weight greater than 19 and R represents a lower alkyl group containing from l4 carbon atoms, preferably ethyl bromoacetate, yields the corresponding l-carbalkoxyl ,2,3,4-tetrahydro-7-alkoxy-2- oxo-l-naphthaleneacetic acid lower alkyl ester (Vla, R-'=lo wer alkyl). Said last-named compound is treated with a base, preferably an aqueous solution of an alkali metal hydroxide under conditions will selectively hydrolyze only the primary carboxylic acid ester group to obtain the corresponding 1 -carbalkoxyl ,2,3,4-tetrahydro-7-alkoxy-2-oxol naphthaleneacetic acid (Vlb, R-=H). Said last-named compound is converted to the corresponding acid Lazide (Vll) which is not isolated and rearranges spontaneously to the compound of this invention, 2-azido l-carboxy-l,2,3,4- tetrahydro-2-hydroxy-7-alkoxy-l-naphthaleneacetic acid ylactone lower alkyl ester (l, R=lower alkyl, R=COO lower alkyl). L

When it is desired to obtain the compounds of this invention in which R represents a lower alkyl group, 7-alkoxy-2- tetralone of formula [V is treated with a haloacetic acid lower alkyl ester of the formula XCl-LCOOR in which X and R are as defined above in the presence of an organic base to yield the corresponding 1 ,2,3,4-tetrahydro-7-alkoxy-2-oxol naphthaleneacetic acid lower alkyl ester (Vlll). Said lastnamed compound is treated with an alkali metal hydride and a lower alkyl chloride, bromide, or iodide to yield the corresponding l,2,3,4-tetrahydro l-(lower alkyl)-7-alkoxy-2- oxo-l-naphthaleneacetic acid lower alkyl ester (lXa, R =lo wer alkyl). Said last-named compound is treated with a base, preferably an aqueous alkali metal hydroxide under conditions which will hydrolyze the primary carboxylic acid ester group, to obtain the corresponding l,2,3,4-tetrahydro-l- (lower alkyl)-7alkoxy-2-oxo-l-napthaleneacetic acid (lXb, R =H). The latter compound is converted to the conesponding acid azide, l-azideocarbonylmethyl-l-(lower alkyl)- l,2,3,4-tetrahydro-7-alkoxy-2-oxonaphthalene (X), and said last-named compound rearranges spontaneously to yield the corresponding compound of this invention 2-azido-l,2,3,4- tetrahydroQ-hydroxyJ-alkoxy- 1 -(lower alkyl l naphthaleneacetic acid 7 -lactone (l, R and R=lower alkyl). The spontaneous rearrangement of the acid azides of formulas VII and X may be effected by allowing a solution of the above azides to stand either at room temperature or under refrigeration.

The following formulas will illustrate this invention.

It-O C CHzCOOR VIII.

lXazR =lower alkyl,

R lower alkyl DETAILED DESCRIPTION OF TI-IE INVENTION More specifically, 2,7-dihydroxynaphthalene is treated with an alkali metal hydroxide, preferably aqueous sodium hydroxide and with a di-(lower alkyl) sulfate preferably methyl sulfate, to yield the corresponding 2,7-dialkorrynaphthalene, preferably 2,7-dimethoxynaphthalene (III). Said last-named compound is treated with an alkali metal in a lower allranol, preferably sodium in ethanol, to yield the corresponding 7-alkoxy-2-tetralone, preferably 7-methoxy-2-tetralone (IV). The above two steps are carried out in a manner similar to that described by Comforth and Robinson in J. Chem. Soc. 1949, p. 1861.

When it is desired to obtain the compounds of this invention in which R represents the group COOIR in which R is as defined above, said last-named compound of formula IV is treated with an alkali metal hydride, preferably sodium hydride and a di-(lower alltyl) carbonate, preferably dimethylcarbonate, in a manner similar to that described by Colvin et al. in Chemistry and Industry 1966, p. 2130, to yield the corresponding l ,2,3 ,4-tetrahydro-7-alkoxy-2-oxol naphthalenecarboxylic acid lower alkyl ester, preferably 1 ,2,3,4-tetrahydro-7-methoxy-2-oxol -naphthalencarboxylic acid methyl ester (V). Treatment of said last-named compound with an alkali metal hydride, preferably sodium hydride, and with a haloacetic acid ester of the formula XCH,C()OR in which X and R are as defined above, preferably ethyl bromoacetate, yields the corresponding lcarbalkoxyl ,2,3,4,-tetrahydro7-allroxy-2oxo- I naphthaleneacetic acid lower alkyl ester, preferably l-carbomethoxyl ,2,3 ,4 -tetrahydro-7-methoxy-2-oxol naphthaleneacetic acidethyl ester (Vla, R =-C,Ii Treatment of said last-named compound with an alkali metal hydroxide, preferably l0 percent aqueous sodium hydroxide, under conditions which will selectively hydrolyze only the primary ester group, preferably in methanol at room temperature for a period of time of from 8 to 24 hours, preferably about 16 hours, yields the corresponding naphthaleneacetic acid, l-carbalkoxyl ,2,3,4-tetrahydro-7alkoxy-2-oxol naphthaleneacetic acid, preferably I-carbomethoxy-l,2,3,4- tetrahydro-7-methoxy-2-oxol -naphthaleneacetic acid (Vlb, R*-=I-I).

Said last-named free acid of formula Vlb may either be converted to the corresponding acid halide, for example, to the chloride by treatment with oxalyl chloride, and then treated with sodium azide to obtain the corresponding acid azide. Al-

I, R =lower allryl ternatively, it may be converted to a mixed anhydride, for example by treatment with ethyl chloroforrnate in the presence of an organic base, preferably at triethylamine, and the latter mixed anhydride may be treated at temperatures within the range of from -20 C. to 20 C., preferably at -l0 C., with an aqueous solution of sodium an'de. Extraction of the reaction mixture with a water-immiscible inert solvent, preferably diethyl ether, yields the corresponding azide, l-carbalkoxy- 1 ,2,3,4-tetrahydro-7-alkoxy-2-oxol -naphthaleneacetic acid azide, preferably l-carbomethoxyl ,2,3 ,4-tetrahydro-7- methoxy-Z-oxol -naphthaleneacetic acid azide (VII Said last-named compound, upon being allowed to stand in solution in an inert solvent, preferably diethyl ether, rearranges spontaneously at temperatures within the range of from -20 to 20 C., preferably at about l0 C., to yield the corresponding compound of this invention, 2-azido-l-carboxyl ,2,3,4tetrahydro2-hydroxy-7-alkoxyl -naphthaleneacetic acid y-lactone lower alkyl ester, preferably 2-azidol -carboxy- I ,2,3 ,4-tetrahydro-2-hydroxy-7-methoxyl -naphthaleneacetic acid -y-lactone methyl ester (I, R==CH,, R=COOCH,).

When it is desired to prepare the compounds of this invention in which R represents a lower alltyl group a 7-alkoxy 2- tetralone of formula IV, preferably 7-methoxy-2-tetralonc, is treated with a haloacetic acid lower alkyl ester of the formula )(Cl-I,,C0 )R in which X and R are as defined above, preferably ethyl bromoacetate, in the presence of an organic base, preferably pyrrolidine, to yield the corresponding 1 ,2,3 ,4-tetrahydro-7-alkoxy-2'oxol -naphthaleneacetic acid lower alltyl ester of formula Vlll, preferably 1,2,13,4- tetrahydro-7-methoxy-2-oxo-l-naphthaleneacetic acid ethyl ester. Said last-named compound of formula VIII is treated with an alkali metal hydride, preferably sodium hydride, followed by treatment with a lower alkyl chloride, bromide, or iodide containing from one to four carbon atoms, preferably methyl iodide, to yield the corresponding l,2,3,4tetrahydrol-(lower alltyl)-7-all oxy-2-oxo-l-naphthaleneaeetic acid lower alltyl ester, preferably l,2,3,4-tetrahydro-l-methyl-7- methoxy-Z-oxo-lnaphthaleneacetic acid ethyl ester (IXa, It 0H Treatment of said last-named compound with an aqueous alkali metal hydroxide, preferably I0 percent sodium hydroxide, under conditions which will hydrolyze the primary carboxylic ester group preferably in methanolic solution at a temperature of from l0-30 (1., preferably at room temperature, and for periods of time of from 8-24 hours, preferably for about 16 hours, yields the corresponding l,2,3,4-

R=l-l). SAid last-named compound is treated with ethyl chloroformate in the presence of an organic base, preferably 5 triethylarnine, to obtain the corresponding mixed anhydride which is not isolated but is treated with an aqueous solution of an alkali metal azide, preferably sodium azide, at temperatures within the range of from 20 C. to 20 C., preferably at about l C., to obtain the corresponding acid azide. Alternatively, that same compound may also be obtained by treating the compound of formula IXb with oxalyl chloride to obtain the corresponding acid chloride, which is not isolated by which is treated immediately with an aqueous solution of an alkali metal azide in the same manner as described above. In this way there is obtained the corresponding l-azidoearbonymethyl- 1-( lower alkyl)- 1 ,2,3,4-tetrahydro-7-alkoxy-2- oxo-naphthalene, preferably l-azidocarbonylmethyI-lmethyl- 1 ,2,3 ,4-tetrahydro-7-methoxy-2-oxo-naphthalene (X). Said last-named compound is being allowed to stand in solution in diethyl ether at a temperature within the range of from 10 C. to 10 C., for periods of time of from 5-20 days, preferably for about days, to yield the corresponding compound of this invention 2-azido-l ,2,3,4-tetrahydro-1-hydroxy- 7-alkoxy-1-(lower aIkyl)-1-naphthaleneacetic acid -y-lactone preferably 2-azido-l,2,3,4-tetrahydro-2-hydroxy-7-methoxyl-methyl- 1 -naphthaleneacetic acid y-lactone (1, R=R=Cl-l,).

The following examples are illustrative of this invention.

EXAMPLE 1 2,7-DIMETHOXYNAPHTHALENEUII) In a manner similar to that described by Comforth and Robinson in J. Chem. Soc. 1949, p. 1861, 2,7-dihydroxynaphthalene (200 g.) is mixed with 2N sodium hydroxide (1120 cc.), and Lmethyl sulfate (250 c is added at once. The mixture is stirred and cooled to keeii the reaction in the 40-50 C. range. When the reaction has subsided (ca. 45 min.), more 2N sodium hydroxide (560 cc.) and methyl sulfate (120 cc.) are added. The mixture is stirred overnight at room temperature, and excess methyl sulfate is destroyed by warming for 55 hour on a steam bath with stirring. The warm liquid is acidified and extracted with chloroform, the chloroform layer washed twice with a little 2N sodium hydrox- 1 ide and evaporated. The residue is crystallized from etha iol-to 1 yield the title compound with m.p. 140 C. 73,33 1625,

1500, 1455, 1375, 1150, I025, 850, 825 cm"'".

EXAMPLE 2 7-METHOXY-2-TETRALONE( IV) In a manner similar to that described by Cornforth and Robinson cited above, 300 g. of sodium metal are added over 45 minutes to a solution of 2,7-dimethoxynaphthalene (200 g.) in boiling ethanol (2,000 cc.). More etha nol (500 cc.) is added and heating is continued under reflux until the metal has disappeared (about 40 minutes). Water 1,000 cc.) is cautiously added and most of the alcohol removed under reduced pressure. The residue is mixed with more water (300 cc. and the lower aqueous layer is separated as far as possible and extracted twice with a little dioxan which is combined with the oily upper layer. Water (250 cc.) and hydrochloric acid ($1.18) are added until the mixture is acid to Congo red. More acid (30 cc.) is added and the liquid is heated on a steam bath for 1% hour. The lower oily layer is separated; the aqueous layer is diluted with water (1 liter), separated from more oil, and extracted three times with small quantities of chloroform. The combined oil and chloroform extracts are stirred with saturated aqueous sodium hydrogen sulfite (500 cc.) overnight, the resulting mass is triturated with ether, the solid is collected, washed well with ether, dissolved in hot water (2.5 liters) and treated with solid sodium carbonate until no more oil oil is extracted with chloroform, the solvent .'=....PB"9.? .L re ar the title pound with b.p. 120 c./0.s mm. Hg, and m.p. 25C., 5 53 1725, 1620, 1500, 1125, 1100 cm"".

EXAMPLE 3 l ,2,3 ,4-TEI'RAHYDRO-7-ME'I'I-IOXY-2-OXO- l NAP'I'HALENECARBOXYLIC ACID METHYL ESTER In a manner similar to that described by Colvin et al. in Chemistry and Industry 1966, p. 2130, a mixture of 7-methoxy-Z-tetralone (88 g.) in dry benzene (500 cc.) containing ab- 5 solute methanol (2 cc.) is treated with sodium hydride (27.6 g.

. 1.2 equiv. 54 percent dispersion in oil) under an atmosphere of dry nitrogen, with cooling. Dimethyl carbonate (450 g. 10 equiv.) is added to the solution and the resulting mixture is refluxed for 3 hours. The solution is cooled to about 0. C. and decomposed with 30 percent acetic acid. Water (250 cc). is added and the solution is extracted with ether. The combined ether extracts are dried over sodium sulfate. After evaporation of the solvents the residue is crystallized from toluene to yield the title compound with m.p. 49-s0 c., vfifl 1710, 1600,

1075, 1050, cm"" Anal. Calcd. C, 66.65; H, 6.02 percent L Found: C, 66.86; H, 6.10 percent EXAMPLE 4 I-CARBOMETHOXY-I ,2,3 ,4-TETRAHYDRO-7- METHOXY-Z-OXO- l -NAPHTHALENACETIC ACID ETI-IYL ESTER (Vla) To a stirred mixture of sodium hydride 19.0 g., 1.05 equiv., 50 percent suspension in mineral oil) in dry benzene l ,200cc.) 1 ,2,3,4-tetrahydro-7-methoxy-Z-oxo- 1 naphthalenecarboxylic acid methyl ester (94.0 g., 1.0 equiv.) in solution in dry benzene ml.) is added with cooling under nitrogen. The mixture is stirred at room temperature for l and a b hours and cooled in an ice bath while ethyl bromoacetate (60 ml., 1.5 equiv.) is added slowly from a dropping funnel over a period of A hour. After foaming ceases, the mixture is slowly heated and refluxed overnight. Afier cooling, water (500 cc.) is added, and the aqueous layer extracted with benzene (3X70 cc.). The combined benzene extracts are washed with water and dried over sodium sulfate. Evaporation of the solvent gives the title compound as an oil with 15, 31 1740 -1720, 1040 omt flm EXAMPLE 5 1-CARBOMETHOXY- l ,2,3,4-TETRAHYDRO-7- METHOXY-2-OXO- 1 -NAPHTHALENEACE'I'IC ACID mair.

Anal. cal'd.: C, 61.64; H, 5.52 percent Found: C, 61.38; H, 5.75 percent EXAMPLE 6 2-AZ1D0- I-CARBOXY-1 ,2,3,4-TETRAHYDRO-2- I-IYDROXY-7-METI'IOXY-l-naphthaleneacetic ACID -yLACT ONE METHYL ESTER L(l, R=CI-I,, R=COOCH,)

To a magnetically stirred, ice cooled solution of l-carbomethoxy l ,2,3,4-tetral1ydro-7methoxy-2-oxolnaphthaleneacetic acid (10 g.) in dry tetrahydrofuran (250 cc.) is added under an atmosphere of dry nitrogen, triethylamine (5 cc.) and ethyl chloroformate (3.8 cc.). A white chalky precipitate fon'ns immediately; after being stirred for two hours at C. the suspension is cooled to about l0 C. and is treated with a solution of sodium azide g.) in

distilled water cc.). The suspension clears rapidly, leaving 10 stand at room temperature and undergoes spontaneous rearrangement within minutes to yield the title compound with m.p. 99 C. after crystallization from methanol, 'ygg 2120, 1810, 1730, 1040 cm."'.

Anal. Calc'd: C, 56.78; H, 4.77; N, 13.24 percent L Found: C, 56.82; H, 4.933 N, 13.22 percent EXAMPLE 7 l ,2 ,3 ,4-TETRAHYDRO-7-METl-lOXY-2-OXO l NAlPH'l'l-lALENEACE'llC AClD ETHYL ESTER (Vlll) 7-Methoxy-2-tetralone (41 g.) is dissolved in benzene (500 ml.) under nitrogen and 150 ml. is distilled off to dry the solution. After cooling to room temperature, pyrrolidine cc., 35

1.75 equiv.) is added and the solution is refluxed overnight under a water trap. 100 ml. benzene is distilled obi, ethyl bromoacetate (80 cc., 3 equiv.) is added dropwise and the mixture is refluxed overnight. After cooling the crystalline material is filtered, washed thoroughly with benzene and decomposed by refluxing in 95 percent ethanol (500 ml.) for 1 hour. The ethanol is panially evaporated, water (300 ml.) is added and the solution is extracted with chloroform to yield the title compound as an oil with y 1500, 1050 cm.'. EXAMPLE 8 1,2,3 ,4-TETRAHYDRO l METHYL-7-METHOXY-2-OXO- I-NAPHTHALENEACETIC AClD ETll-lYL ESTER (lXa) max.

1 ,2,3,4Tetrahydro-7-methoxy-2oxol naphthalenenacetic acid ethyl ester (200 g.) in dry benzene (3000 ml.) under dry nitrogen, is treated with sodium hydride (44 gm. of percent dispersion in oil) by stirring for 6 hours at room temperature. Methyl iodide (200 ml. 1.5 equiv.) is added and the reaction mixture is refluxed for 18 hours. Alter being cooled, the reac- 55 tion mixture is washed with ice water, dried with magnesium sulfate, filtered, and evaporated, to yield the title compound as an oil, vigi 735, 1725, 1620, 1500. 1050 cm."",NI /1R (CDCll 16.2, 8.6.

EXAMPLE 9 l ,2,3 ,4-TETRAHYDRO- 1 -METl-lYL-7METHOXY-2-OXO- l-NAlPHTAl-lALENEACE'llC ACID (lXb) l ,2,3 ,4-Tetrahydrol methyl-7-methoxy-2-oxol naphthaleneacetic acid ethyl ester (20.0 g.) is dissolved inmethanol (100 ml.), Lmixed with one equivalent of 10 percent aqueous sodium hydroxide in methanol and stirred at room temperature overnight. After removing most of the methanol under reduced pressure water (250 ml.) is added and the product is isolated by ether extraction after acidification with 10 percent hydrochloric acid. The combined ether extracts are dried over sodium sulfate and evaporated to give the title compound with m.p. 110l 12 C. after crystallization from ethanol, 2,39 3590, 1e30, 1040 em NMR (coon) m2, 8.6

- hydroxy-7-methoxyl naphthaleneacetic EXAMPLE 1o l-AZlDOCAlRBONYLYL l-ME'I'HYL- 1 ,2,3,4 TETRAHYDRO-7METHOXY-2-OXO-NAPHTHALENE To a magnetically stirred ice-cooled solution of 1,2,15,4- tetrahydrol-methyl-lmethoxyQ-oxol naphthaleneacetic acid (3 g.), in dry tetrahydrofuran (25 ml.) is added by means of syringe under an atmosphere of dry nitrogen, triethylamine (2.0 ml.) and then ethyl chloroformate (1.25 ml.). A white chalky precipitate forms immediately. After being stirred for two hours at 0 C., the suspension is further cooled to about l0 C. and is treated with a solution of sodium azide 1.85 g.) in distilled water (3 ml.). The suspension clears, leaving a white gummyprecipitate and a pale yellow solution. After being stirred during a further 1 hour at l0 C., the reaction mixture is diluted with cold ether (50 ml.) and is decanted from the insoluble gummy residue which is rinsed with additional ether (2X50 ml.). The combined ethereal phases are dried over magnesium sulfate and are evaporated without heating to yield the title compound as an oil,'y,%g, 2l40, 1710 cmf EXAMPLE 1 1 Z-AZIDO- l ,2,3 ,4HTETRAHYDRO-2-HYDROXY-7- METHOXY- l-NAPHTHALENEACETIC ACID 7- LAC!- ONE (I,R=R'=CH l-Azidocarbonylmethyl- 1 methyl- 1 ,2,3 ,4-tetrahydro-7- methoxy-Z-oxomaphthalene rearranges into the title compound upon standing in ethereal solution at about 0" C. for 10 days. The title compound is crystallized from ether to m.p.

Anal. cale'az'c, 61.53; H, 5.53;N, 15.38 percent Found: C, 61.77; H, 5.64; N, 15.40 percent We claim:

1. A product selected from those of the formula 0 II R RO- j wherein R represents lower alkyl containing from one to four carbon atoms; and R is selected from the group which consists of lower alkyl containing from one to four carbon atoms and the group COOR, represents lower alkyl containing from one to four carbon atoms.

2. 2-Azido-l-carboxy-1 ,2,3 ,4-tetrahydro-2-hydroxy-7- methoxy-l-naphthaleneacetic acid 'y-lactone methyl ester, as claimed in claim 1..

3. 2-Azidol ,2,3,4tetrahydro-Zhydroxy-7-methoxyl methyl-l-napthaleneacetic acid 7-lactone, as claimed in claim 1.

4. The process of allowing a solution of l-carbomethoxyl ,2,3 ,4-tetrahydro-7-methoxy-2-oxol -naphthaleneacetic acid azide to stand whereby spontaneous rearrangement occurs, and recovering 2-azido-l-carboxy-l,2,3,4-tetrahydro-2- acid 'y-lactone methyl ester.

5. The process of allowing a solution of l-azidocarbonylmethyl- 1 methyl- 1 ,2,3,4-tetrahydro-7-methoxy-2-oxonaphthalene to stand whereby spontaneous rearrangement occurs, and recovering 2-azido-l,2,3,4-tetrahydro-2-hydroxy-7- methoxy- 1 methyl- 1 naphthaleneaceu'c acid 'y-lactone.

1 t 0 i i

Claims

2. 2-Azido-1-carboxy-1,2,3,4-tetrahydro-2-hydroxy-7-methoxy-1-naphthaleneacetic acid gamma -lactone methyl ester, as claimed in claim 1.
3. 2-Azido-1,2,3,4-tetrahydro-2-hydroxy-7-methoxy-1-methyl-1-napthaleneacetic acid gamma -lactone, as claimed in claim 1.
4. The process of allowing a solution of 1-carbomethoxy-1,2,3,4-tetrahydro-7-methoxy-2-oxo-1-naphthaleneacetic acid azide to stand whereby spontaneous rearrangement occurs, and recovering 2-azido-1-carboxy-1,2,3,4-tetrahydro-2-hydroxy-7-methoxy-1-naphthaleneacetic acid gamma -lactone methyl ester.
5. The process of allowing a solution of 1-azidocarbonyl-methyl-1-methyl-1,2,3,4-tetrahydro-7-methoxy-2-oxo -naphthalene to stand whereby spontaneous rearrangement occurs, and recovering 2-azido-1,2,3,4-tetrahydro-2-hydroxy-7-methoxy-1-methyl-1-naphthaleneacetic acid gamma -lactone.