Finding an "ISO" for MS-DOS 6.22 can be tricky because the original OS was distributed on 1.44MB floppy disks, not CD-ROMs. Most "working" ISOs you find online are actually "Bootable CD" wrappers that contain the floppy disk images.
Are you trying to run this in a or on real hardware ?
Use a tool like Rufus or ImgBurn to write the ISO to a CD-R.
Many 1990s classics like DOOM , Duke Nukem 3D , and Oregon Trail require the specific memory management (HIMEM.SYS and EMM386) of DOS to run with sound and music.
Point the virtual optical drive to your MS-DOS 6.22 ISO. 2. On Physical Hardware
Once you have your image, the process for getting it running depends on your environment. 1. In Virtual Machines (VirtualBox, VMware) Virtual machines are the easiest way to run DOS.